Rimonabant-d10 is deuterium labeled Rimonabant. Rimonabant (SR141716) is a highly potent, brain penetrated and selective central cannabinoid receptor (CB1) antagonist with a Ki of 1.8 nM. Rimonabant (SR141716) also inhibits Mycobacterial membrane protein Large 3 (MMPL3).
体外研究 (In Vitro)
Stable heavy isotopes of hydrogen, carbon, and other elements have been incorporated into drug molecules, largely as tracers for quantitation during the drug development process. Deuteration has gained attention because of its potential to affect the pharmacokinetic and metabolic profiles of drugs[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
473.85
Formula
C22H11D10Cl3N4O
CAS 号
929221-88-5
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Russak EM, et al. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019;53(2):211-216.
[2]. Leite, C.E., et al. Rimonabant: An antagonist drug of the endocannabinoid system for the treatment of obesity. Pharmacol Rep 61 217-224 (2009).
[3]. Seely KA, Brents LK, Franks LN, Rajasekaran M, Zimmerman SM, Fantegrossi WE, Prather PL. AM-251 and rimonabant act as direct antagonists at mu-opioid receptors: Implications for opioid/cannabinoid interaction studies. Neuropharmacology. 2012 Oct;63(5):905-15.
[4]. Zhang B, et al. Crystal Structures of Membrane Transporter MmpL3, an Anti-TB Drug Target. Cell. 2019 Jan 24;176(3):636-648.e13.
[5]. Erdozain, A. M. et al. The inverse agonist effect of rimonabant on G protein activation is not mediated by the cannabinoid CB1 receptor: Evidence from postmortem human brain Biochemical Pharmacology (2012), 83(2), 260-268.
SR 11302 is an activator protein-1 (AP-1) transcription factor inhibitor. SR 11302 is a retinoid that specifically inhibits AP-1 activity without activating the transcription of retinoic acid response element (RARE)[1].
IC50 & Target
AP-1[1]
体外研究 (In Vitro)
SR 11302 (SR11302) show strong anti-AP-1 activity with selective binding with RARα and RARγ, but not with RARβ and RXRα[1]. SR 11302 (SR-11302; 1 μM) inhibits AP-1 transcription factor activity and decreases aldosterone levels by 61.9% in hypoxia-treated cells[2]. SR 11302 (SR-11302; 2 µM; 48 hours) inhibits Helicobacter pylori (H. pylori)-induced cell proliferation in adenocarcinoma gastric (AGS) cells[3]. SR 11302 (2 µM; 24 hours) inhibits H. pylori-induced expression of β-catenin and c-myc in AGS cells[3].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
SR 11302 (SR11302; low dose 0.5 mg/kg and high dose 1 mg/kg body weight; orally gavaged daily) treatment reduces the total vascular lesion number and lesion size in Vldlr-/- mice in a dose-dependent manner[4].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
Vldlr-/- mice[4]
Dosage:
Low dose 0.5 mg/kg and high dose 1 mg/kg body weight
Administration:
Orally gavaged daily from P5 to P15
Result:
High-dose from P5 to P15 reduced the total vascular lesion number by 48% and decreased the lesion size by 40%, without detectable signs of toxicity in mice, including no change in body weight.
分子量
376.53
Formula
C26H32O2
CAS 号
160162-42-5
运输条件
Room temperature in continental US; may vary elsewhere.
将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
*以上所有助溶剂都可在 上海金畔生物科技有限公司 网站选购。
参考文献
[1]. C Huang, et al. Blocking activator protein-1 activity, but not activating retinoic acid response element, is required for the antitumor promotion effect of retinoic acid. Proc Natl Acad Sci U S A. 1997 May 27;94(11):5826-30.
[2]. Bradley A Maron, et al. Upregulation of steroidogenic acute regulatory protein by hypoxia stimulates aldosterone synthesis in pulmonary artery endothelial cells to promote pulmonary vascular fibrosis. Circulation. 2014 Jul 8;130(2):168-79.
[3]. Eunyoung Byun, et al. Activation of NF-κB and AP-1 Mediates Hyperproliferation by Inducing β-Catenin and c-Myc in Helicobacter pylori-Infected Gastric Epithelial Cells. Yonsei Med J. 2016 May;57(3):647-51.
[4]. Ye Sun, et al. Inflammatory signals from photoreceptor modulate pathological retinal angiogenesis via c-Fos. J Exp Med. 2017 Jun 5;214(6):1753-1767.
SR9243 is a liver-X-receptor (LXR) inverse agonist that induces LXR-corepressor interaction.
体外研究 (In Vitro)
SR9243 specifically targets LXR and downregulates LXR-mediated gene expression, dose-dependently suppresses LXRα- and LXRβ-dependent transcription at nanomolar concentrations, and potently inhibits LXR-driven luciferase activity in cultured cancer cells. SR9243 potently reduces cancer cell viability at nanomolar concentrations (IC50 appr 15-104 nM) in prostate (PC3 and!DU-145), colorectal (SW620 and HT29), and lung (HOP-62 and NCI-H23) cancer cell lines. And the colony-forming capacity of cancer cells is also significantly loared by SR9243 in a dose-dependent manner. SR9243 is a potent inhibitor of lipogenic gene expression that selectively kills cancer cells by depleting intracellular lipids. Combination of cancer cell media with oleate, stearate, and palmitate in combination completely rescues cancer cell viability in cancer cells. Fatty acid supplementation also rescues the viability of SW620 cells in which glycolysis is substantially disrupted[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
SR9243 is able to profoundly inhibit tumor glycolysis, lipogenesis, and induce apoptotic cancer cell death without promoting weight loss in vivo. SR9243 inhibits tumor growth without profoundly repressing glycolytic gene expression, and inhibits tumor growth and lipogenesis without hepatotoxicity or inflammation in vivo[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
626.62
Formula
C31H32BrNO4S2
CAS 号
1613028-81-1
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Flaveny CA, et al. Broad Anti-tumor Activity of a Small Molecule that Selectively Targets the Warburg Effect and Lipogenesis. Cancer Cell. 2015 Jun 24. pii: S1535-6108(15)00183-X.
Cell Assay [1]
Cancer cells are plated at low-density (5×103) cells per well. Cells are then treated with either DMSO vehicle control, SR9243 (100 nM) or SR9243 (10 μM) and allowed to grow for 4 days. Colonies are then fixed with Formaldehyde (1%) and stained with Crystal violet solution (0.05% w/v)[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration [1]
Mice[1] C57BL/6J, Nu/Nu and Ob/Obmice are used in the assay. Mice are housed in sterile ventilated cages, fed a standard diet, and provided water ad libitum. Mice are treated after two weeks of acclimation. Mice are monitored daily for signs of illness, pain, or severe weight loss. All mice are humanely euthanized using CO2 followed by cervical dislocation. For liver lipid content analysis 8-week old male Ob/Ob mice are fed a high fat diet (60% kcal/fat, 20% carbohydrate) for the duration of the experiment and are treated with vehicle or SR9243 for 3 days. Mice are injected (i.p.) with either vehicle (10% DMSO, 10% Tween-80) or SR9243 (30 mg/kg) once daily[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Flaveny CA, et al. Broad Anti-tumor Activity of a Small Molecule that Selectively Targets the Warburg Effect and Lipogenesis. Cancer Cell. 2015 Jun 24. pii: S1535-6108(15)00183-X.
SR-3029 is a potent and ATP competitive CK1δ and CK1ε inhibitor, with IC50s of 44 nM and 260 nM, respectively, and Kis of 97 nM for both kinases.
IC50 & Target[1]
CKIδ
44 nM (IC50)
CKIϵ
260 nM (IC50)
CDK6/cyclin D3
427 nM (IC50)
CDK6/cyclin D1
428 nM (IC50)
CDK4/cyclin D3
368 nM (IC50)
CDK4/cyclin D1
576 nM (IC50)
FLT3
3000 nM (IC50)
体外研究 (In Vitro)
SR-3029 is a potent CK1δ/CK1ε inhibitor, with IC50s of 44 nM and 260 nM, respectively. SR-3029 is ATP competitive, with Kis of 97 nM for CK1δ/CK1ε. SR-3029 also blocks CDK6/cyclin D3, CDK6/cyclin D1, CDK4/cyclin D3, CDK4/cyclin D1 and FLT3, with IC50s of 427, 428, 368, 576, and 3000 nM, respectively. SR-3029 shows inhibitory effects on A375 cells, with an EC50 of 86 nM[1]. CK1δ is a necessary and sufficient driver of Wnt/β-catenin signaling in human breast cancer. SR-3029 shows less potent activities against MCF7 and T47D breast cancer cells and the MCF10A cell line, which express low amounts of CK1δ[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
SR-3029 (20 mg/kg daily i.p.) exibits anti-tumor effects in rthotopic MDA-MB-231, MDA-MB-468 (TNBC), SKBR3 and BT474 (HER2+) tumor xenografts with no overt toxicity in mice. SR-3029 (20 mg/kg daily i.p.) also effectively inhibits the growth of tumor in primary patient-derived xenograft (PDX) models. In addition, SR-3029 (20 mg/kg, i.p.) strongly reduces the expression of nuclear β-catenin in tumors of mice[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
480.45
Formula
C23H19F3N8O
CAS 号
1454585-06-8
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Bibian M, et al. Development of highly selective casein kinase 1δ/1ε (CK1δ/ε) inhibitors with potent antiproliferative properties. Bioorg Med Chem Lett. 2013 Aug 1;23(15):4374-80.
[2]. Rosenberg LH, et al. Therapeutic targeting of casein kinase 1δ in breast cancer. Sci Transl Med. 2015 Dec 16;7(318):318ra202.
Kinase Assay [1]
Briefly, final assay concentrations for CK1δ, Ulight peptide substrate (ULight-Topo-Ila(Thr1342) peptide) and ATP are 2 nM, 200 nM and 20 μM respectively. The reaction is performed at room temperature in a 10 μL final volume (384-well low volume plate) containing the following: 50 mM Hepes, pH 7.5, 5 mM MgCl2, 0.1 mg/mL bovine serum albumin, 1 mM dl-dithiothreitol, 0.01% Triton X-100 and 1% DMSO. After 10 min, the reaction is terminated by addition of 10 μL of 4 nM Eu-anti-p-Topo-Ila in Lance Detection Buffer. The fluorescent signal is detected using a plate reader. 10 point does-response curves with 3-fold dilutions starting from 10 μM for each compound (SR-3029) is generated in duplicate and data fit to a four parameter logistic[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Assay [1]
Human A375 melanoma cells are cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum, 1% penicillin/streptomycin and 1× MEM Non-Essential Amino Acids at 37°C, 5% CO2. To evaluate the anti-proliferative activity of newly synthesized CK1δ/ε inhibitors, each compound (SR-3029) is subjected to MTT assays against A375 melanoma cells and their EC50 values are determined. Briefly, A375 melanoma cells are plated into a 96-well plate and treated with a series of concentrations of each new inhibitor, vehicle (DMSO) or with SR-3029 or SR-1277 (positive controls). MTT assays are performed four days after treatment and data are analyzed using the GraphPad Prism5[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration [2]
Stable pools of MDA-MB-231-Luc, MDA-MB-231, MDA-MB-468, SKBR3, or BT474 cells are established by injection of 2 × 106 cancer cells into the mammary fat pads of 6-week-old female athymic nude mice. Establishment of BCM-4013 patient-derived xenografts is performed. Briefly, fresh xenograft tumor fragments (∼1 mm3) are transplanted into the cleared mammary fat pad of recipient SCID/Bg mice. Mice are treated with SR-3029 or vehicle (10:10:80, DMSO:Tween-80:Water) at 20 mg/kg daily by i.p. injection. Tumor volumes are measured as the indicated intervals using calipers or by luminescence imaging with the IVIS 100 imager after subcutaneous injection of luciferin (15 mg/mL). Average radiance (p/s/cm2/sr) is determined from tumor region-of-interest (ROI) using Living-Image analysis software[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Bibian M, et al. Development of highly selective casein kinase 1δ/1ε (CK1δ/ε) inhibitors with potent antiproliferative properties. Bioorg Med Chem Lett. 2013 Aug 1;23(15):4374-80.
[2]. Rosenberg LH, et al. Therapeutic targeting of casein kinase 1δ in breast cancer. Sci Transl Med. 2015 Dec 16;7(318):318ra202.
SR-717 is a non-nucleotide STING agonist with EC50s of 2.1 μM and 2.2 μM in ISG-THP1 (WT) and ISG-THP1 cGAS KO (cGAS KO) cell lines, respectively. SR-717 is a stable cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) mimetic. Antitumor activity[1].
体外研究 (In Vitro)
SR-717 activates STING by inducing the same closed conformation, which thereby provides an avenue to explore this class of systemic STING agonist in diverse contexts, including antitumor immunity[1]. SR-717 (3.8 μM) induces the expression of PD-L1 in THP1 cells and in primary human peripheral blood mononuclear cells in a STING-dependent manner[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
SR-717 (30 mg/kg intraperitoneal once-per-day for 1 week) shows antitumor activities in WT or Stinggt/gt mice[1]. SR-717 (30 mg/kg intraperitoneally for 7 days) displays antitumor activity; promots the activation of CD8+ T, natural killer, and dendritic cells in relevant tissues; and facilitates antigen cross-priming[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
WT or Stinggt/gt mice[1]
Dosage:
30 mg/kg
Administration:
Intraperitoneally; once-per-day for 1 week
Result:
Maximally inhibited tumor growth.
分子量
351.19
Formula
C15H8F2LiN5O3
CAS 号
2375421-09-1
运输条件
Room temperature in continental US; may vary elsewhere.
SR-4835 是有效，高选择性和 ATP 竞争性的 CDK12/CDK13 双重抑制剂 (CDK12：IC50=99 nM，Kd=98 nM；CDK13：Kd=4.9 nM)。SR-4835 与破坏 DNA 的化学疗法和 PARP 抑制剂协同作用，并引起三阴性乳腺癌 (TNBC) 细胞凋亡。
SR-4835 Chemical Structure
CAS No. : 2387704-62-1
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SR-4835 相关产品
•相关化合物库:
Bioactive Compound Library Plus
Apoptosis Compound Library
Cell Cycle/DNA Damage Compound Library
Kinase Inhibitor Library
Anti-Cancer Compound Library
Anti-Aging Compound Library
Anti-Breast Cancer Compound Library
Anti-Blood Cancer Compound Library
Targeted Diversity Library
生物活性
SR-4835 is a potent, highly selective and ATP competitive dual inhibitor of CDK12/CDK13 (CDK12: IC50=99 nM, Kd=98 nM; CDK13: Kd=4.9 nM). SR-4835 acts in synergy with DNA-damaging chemotherapy and PARP inhibitors and provokes triple-negative breast cancer (TNBC) cell death[1].
IC50 & Target[1]
CDK12
99 nM (IC50)
CDK12
98 nM (Kd)
CDK13
4.9 nM (Kd)
体外研究 (In Vitro)
SR-4835 (90 nM; 0.5-48 hours) suppresses ATM and RAD51 protein levels[1]. SR-4835 inhibits CDK12/CDK13 which triggers intronic polyadenylation site cleavage and suppresses the expression of core DNA damage response proteins[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Western Blot Analysis[1]
Cell Line:
MDA-MB-231 cells
Concentration:
90 nM
Incubation Time:
0.5, 6, 24, 48 hours
Result:
Suppressed ATM and RAD51 protein levels.
分子量
499.36
Formula
C21H20Cl2N10O
CAS 号
2387704-62-1
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Powder
-20°C
3 years
4°C
2 years
In solvent
-80°C
6 months
-20°C
1 month
溶解性数据
In Vitro:
DMSO : 8.93 mg/mL (17.88 mM; ultrasonic and warming and heat to 60°C)
H2O : < 0.1 mg/mL (ultrasonic;warming;heat to 60°C) (insoluble)
SR9009 is a REV-ERBα/β agonist with IC50s of 670 nM and 800 nM for REV-ERBα and REV-ERBβ, respectively.
IC50 & Target
IC50: 670 nM (Rev-ErbBα), 800 nM (Rev-ErbBβ)[1]
体外研究 (In Vitro)
SR9009 dose-dependently increases the REV-ERB-dependent repressor activity assessed in HEK293 cells expressing a chimeric Gal4 DNA Binding Domain (DBD)-REV-ERB ligand binding domain (LBD)α or β and a Gal4-responsive luciferase reporter (SR9009: REV-ERBα IC50=670 nM, REV-ERBβ IC50=800 nM). SR9009 potently and efficaciously suppresses transcription in a cotransfection assay using full-length REV-ERBα along with a luciferase reporter driven by the Bmal1 promoter (IC50=710 nM). SR9009 suppresses the expression of BMAL1 mRNA in HepG2 cells in a REV-ERBα/β-dependent manner. Direct binding of the SR9009 to REV-ERBα is also confirmed using circular dichrosim analysis (Kd=800 nM)[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
While the stress of handling and twice-daily injections caused weight loss in vehicle-treated controls, weight loss of SR9009-treated animals is 60% greater. SR9009 (100 mg/kg ,i.p.) treated mice exhibit a more severe reduction in adiposity. Plasma non-esterified fatty acids (NEFA) are also reduced (23%) along with plasma glucose (19%) in the SR9009 treated animals. In the white adipose tissue (WAT) , SR9009 treatment results in a decrease in expression of genes encoding enzymes involved in triglyceride (TG) synthesis as is also observed in lean mice[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
437.94
Formula
C20H24ClN3O4S
CAS 号
1379686-30-2
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Solt LA, et al. Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists. Nature. 2012 Mar 29;485(7396):62-68.
Cell Assay [1]
HEK293 cells are grown in 96-well plates (1×106/well) and are transiently transfected using Lipofectamine. Cells are transfected with a total of 200 ng of DNA per well consisting of the pGL4 mIL-17 firefly luciferase reporter construct, the pGL4 mIL-17 + CNS-5 firefly luciferase reporter construct, or the pGL4 mIL-17 2kB RORE mutant (100 ng/well) , an actin promoter Renilla reniformis luciferase reporter (50 ng/well), and either control vector alone or the test DNA (full-length RORα or full-length RORγ at 50 ng/well). All 48 human nuclear receptors are represented in the specificity assay and SR9009 is tested at a concentration of 20 μM. The format of the assay is a cotransfection assay with Gal4 DNA binding domain-nuclear receptor fusions in HEK293 cells[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration [1]
Mice[1] For circadian gene expression experiments male C57BL6 mice (8-10 weeks of age) are either maintained on a L:D (12h:12h) cycle or on constant darkness. At circadian time (CT) 0 animals are administered a single dose of 100 mg/kg SR9009 or SR9011 (i.p.) and groups of animals (n=6) are sacrificed at CT0, CT6, CT12 and CT18. Gene expression is determined by real time QPCR.
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Solt LA, et al. Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists. Nature. 2012 Mar 29;485(7396):62-68.
ML-180 (SR1848) is a potent orphan nuclear receptor liver receptor homolog 1 (LRH-1; NR5A2) inverse agonist with an IC50 of 3.7 µM. ML-180 is inactive for steroidogenic factor-1 (SF-1; NR5A1; IC50>10 µM). ML-180 has the potential for LRH-1-dependent cancers[1][2].
IC50 & Target
IC50: 3.7 µM (LRH-1)[1]
体外研究 (In Vitro)
ML-180 (SR1848; 0.01-100 µM; 48 hours) shows diminished capacity to proliferate at concentrations above 1 μM, and the EC50 being roughly 2.8 μM in Huh-7 cells. ML-180 inhibits cell proliferation in an LRH-1-dependent manner[2]. ML-180 (0.5-5 µM; 24 hours) shows a significant inhibition of cyclin-D1 and cyclin-E1 expression in hepatic cells, but has little effect on repression in SK-OV-3 cells[2]. ML-180 (5 µM; 24 hours) leads to a rapid decrease of LRH-1 expression and efficiently represses endogenous LRH-1 signaling[2]. ML-180 (0.5-5 µM; 24 hours) inhibits LRH-1 mRNA expression in a dose-dependent manner[2]. ML-180 (5 μM; 2 hours) rapidly and significantly decreases the mRNA levels of LRH-1 receptor and its downstream targets (CYP19, GATA3, and GATA4) in Huh-7 and HepG2 cells[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Proliferation Assay[2]
Cell Line:
Huh-7 cells
Concentration:
0.01, 0.1, 1, 10, 100 µM
Incubation Time:
48 hours
Result:
Showed diminished capacity to proliferate at concentrations above 1 μM.
Cell Cycle Analysis[2]
Cell Line:
Huh-7 cells
Concentration:
0.5, 1, 5 µM
Incubation Time:
24 hours
Result:
Showed a significant inhibition of cyclin-D1 and cyclin-E1 expression in hepatic cells.
Western Blot Analysis[2]
Cell Line:
Huh-7 cells
Concentration:
5 µM
Incubation Time:
24 hours
Result:
Significantly reduced the LRH-1 protein levels.
RT-PCR[2]
Cell Line:
Huh-7 cells
Concentration:
0.5, 1, 5 µM
Incubation Time:
24 hours
Result:
Inhibited LRH-1 mRNA expression in a dose-dependent manner.
体内研究 (In Vivo)
ML-180 (SR1848; 30 mg/kg; i.p.; daily; for 10 days) has a statistically significant decrease of both LRH-1 and SHP mRNA in adrenal glands and pancreatic tissue[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
8-week-old C57Bl/6J mice[2]
Dosage:
30 mg/kg
Administration:
IP; daily; for 10 days
Result:
Had a statistically significant decrease of both LRH-1 and SHP mRNA in adrenal glands and pancreatic tissue.
分子量
388.89
Formula
C20H25ClN4O2
CAS 号
863588-32-3
运输条件
Room temperature in continental US; may vary elsewhere.
Rimonabant (SR141716) is a highly potent, brain penetrated and selective central cannabinoid receptor (CB1) antagonist with a Ki of 1.8 nM. Rimonabant (SR141716) also inhibits Mycobacterial membrane protein Large 3 (MMPL3).
IC50 & Target[1]
CB1
1.8 nM (Ki)
体外研究 (In Vitro)
Rimonabant could inhibit the growth of Mtb with an MIC of 54 μM. MmpL3, an anti-TB target, is the direct target of rimonabant[2]. Rimonabant itself (10-12-10-3 M, 12 concentrations) inhibits the basal binding of [35S]GTPgS to human cortical membranes in a concentration dependent manner, with a -log IC50 of 4.7±0.2 (IC50 = 20 μM) and a maximal inhibition of 48±2%[3].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
Rimonabant (10 mg/kg by gavage) is fed for 2 weeks to 3-month-old male obese Zucker rats as an impaired glucose tolerance model and for 10 weeks to 6-month-old male obese Zucker rats as a model of the metabolic syndrome. RANTES and MCP-1 serum levels are increased in obese vs lean Zucker rats and significantly reduced by long-term treatment with Rimonabant, which slowes weight gain in rats with the metabolic syndrome. Neutrophils and monocytes are significantly increased in young and old obese vs lean Zucker rats and lowered by Rimonabant. Platelet-bound fibrinogen is significantly enhanced in obese vs lean Zucker rats of both age, and is reduced by Rimonabant [1]. Rimonabant (20 mg daily) exhibits a significant reduction in many cardiometabolic risk factors[4].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
分子量
463.79
Formula
C22H21Cl3N4O
CAS 号
168273-06-1
中文名称
利莫那班
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Seely KA, Brents LK, Franks LN, Rajasekaran M, Zimmerman SM, Fantegrossi WE, Prather PL. AM-251 and rimonabant act as direct antagonists at mu-opioid receptors: Implications for opioid/cannabinoid interaction studies. Neuropharmacology. 2012 Oct;63(5):905-15.
[2]. Leite, C.E., et al. Rimonabant: An antagonist drug of the endocannabinoid system for the treatment of obesity. Pharmacol Rep 61 217-224 (2009).
[3]. Zhang B, et al. Crystal Structures of Membrane Transporter MmpL3, an Anti-TB Drug Target. Cell. 2019 Jan 24;176(3):636-648.e13.
[4]. Erdozain, A. M. et al. The inverse agonist effect of rimonabant on G protein activation is not mediated by the cannabinoid CB1 receptor: Evidence from postmortem human brain Biochemical Pharmacology (2012), 83(2), 260-268.
SR-3677 is a potent and selective ROCK-II inhibitor with an IC50 of ~3 nM.
IC50 & Target[1]
ROCK-II
3 nM (IC50)
ROCK-I
56 nM (IC50)
体外研究 (In Vitro)
SR-3677 has an IC50 of ~3 nM in enzyme and cell based assays and has an off-target hit rate of 1.4% against 353 kinases, and inhibits only 3 out of 70 nonkinase enzymes and receptors. The IC50 value of SR-3677 for ROCK-I is 56±12 nM. The hydrophobic interaction of the benzodioxane phenyl ring with the hydrophobic surface of the pocket is the dominating factor that contributes to the high potency of SR-3677[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
ExVivo: Pharmacology studies shows that SR-3677 is efficacious in both, increasing ex vivo aqueous humor outflow in porcine eyes and inhibiting myosin light chain phosphorylation. Continuous exposure of 25 µM SR-3677 increases the outflow facility by 60% at 1 h perfusion, increasing to 70–80% for the 2–5 h time points[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
408.45
Formula
C22H24N4O4
CAS 号
1072959-67-1
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Feng Y, et al. Discovery of substituted 4-(pyrazol-4-yl)-phenylbenzodioxane-2-carboxamides as potent and highly selective Rho kinase (ROCK-II) inhibitors. J Med Chem. 2008 Nov 13;51(21):6642-5.
Kinase Assay [1]
Assays are performed using the STK2 kinase system from Cisbio. 5 μL mixture of a 1 μM STK2 substrate and ATP (ROCK-I: 4 μM; ROCK-II: 20 μM) in STK-buffer is added to the wells. 20 nL of test compounds (SR-3677) is dispensed. Reaction is started by addition of 5 μL of 2.5 nM. ROCK-I or 0.5 nM ROCK-II in STK-buffer. After 4 h at RT the reaction is stopped by addition of 10 μL of 1x antibody and 62.5 nM Sa-XL in detection buffer[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Feng Y, et al. Discovery of substituted 4-(pyrazol-4-yl)-phenylbenzodioxane-2-carboxamides as potent and highly selective Rho kinase (ROCK-II) inhibitors. J Med Chem. 2008 Nov 13;51(21):6642-5.
StemRegenin 1 is a potent aryl hydrocarbon receptor (AhR) antagonist with IC50 of 127 nM.
IC50 & Target
IC50: 127 nM (AhR)[1]
体外研究 (In Vitro)
StemRegenin 1 (SR1) acts by antagonizing the aryl hydrocarbon receptor (AhR). StemRegenin 1 increases the number of CD34+ cells after 5 to 7 days with an EC50 of ~120 nM. StemRegenin 1 inhibits photoaffinity ligand (PAL) binding (IC50=40 nM) These results support the conclusion that StemRegenin 1 -induced CD34+ cell expansion is mediated through direct binding and inhibition of the AhR[1]. An aryl hydrocarbon receptor antagonist, StemRegenin 1 (SR1), robustly promotes ex vivo expansion of human CD34+ cells. StemRegenin 1 treatment accelerates the proliferation of CD34+ cells and decreases the expression levels of VentX[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
分子量
429.54
Formula
C24H23N5OS
CAS 号
1227633-49-9
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Boitano AE, et al. Aryl Hydrocarbon Receptor Antagonists Promote the Expansion of Human Hematopoietic Stem Cells. Science. 2010 Sep 10;329(5997):1345-8.
[2]. Gao H, et al. Suppression of homeobox transcription factor VentX promotes expansion of human hematopoietic stem/multipotent progenitor cells. J Biol Chem. 2012 Aug 24;287(35):29979-87.
Cell Assay [1]
A quantity of 250,000 CB-derived CD34+ cells are cultured with control conditions (DMSO, 0.01%) or StemRegenin 1 (0.75 μM) for 3 weeks. At this point control cultures had expanded 1080-fold and StemRegenin 1 treated cells expanded 2024-fold relative to starting cell numbers. A quantity of 30 to 30,000 uncultured CD34+ CB-derived cells or a fraction of the final culture equivalent to 30 to 10,000 starting cells are transplanted. The cells are injected intravenously via the retro-orbital route into sub-lethally irradiated (300 rads, 200 rads) 6- to 10-week-old NSG mice. Engraftment is performed within 24 h after irradiation. Engraftment is monitored by flow cytometric analysis of blood obtained via retro-orbital sinus or bone marrow using anti-human CD45 and anti-mouse CD45 antibodies. The mice are sacrificed between 13-16 weeks posttransplantation; bone marrow (from both femurs and tibiae), spleen and thymus are collected for analysis. For secondary engraftment, 50% of the bone marrow from each recipient mouse is transplanted into one secondary sub-lethally irradiated NSG mouse. Fifteen weeks after transplantation, bone marrow is harvested from the secondary mice and analyzed by flow cytometry[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Boitano AE, et al. Aryl Hydrocarbon Receptor Antagonists Promote the Expansion of Human Hematopoietic Stem Cells. Science. 2010 Sep 10;329(5997):1345-8.
[2]. Gao H, et al. Suppression of homeobox transcription factor VentX promotes expansion of human hematopoietic stem/multipotent progenitor cells. J Biol Chem. 2012 Aug 24;287(35):29979-87.
SR9011 is a REV-ERBα/β agonist with IC50s of 790 nM and 560 nM for REV-ERBα and REV-ERBβ, respectively.
IC50 & Target
IC50: 790 nM (Rev-ErbBα), 560 nM (Rev-ErbBβ)[1]
体外研究 (In Vitro)
SR9011 dose-dependently increases the REV-ERB-dependent repressor activity assessed in HEK293 cells expressing a chimeric Gal4 DNA Binding Domain (DBD) – REV-ERB ligand binding domain (LBD) α or β and a Gal4-responsive luciferase reporter (REV-ERBα IC50=790 nM, REV-ERBβ IC50=560 nM). SR9011 potently and efficaciously suppresses transcription in a cotransfection assay using full-length REV-ERBα along with a luciferase reporter driven by the Bmal1 promoter (SR9011 IC50=620 nM). SR9011 suppresses the expression ofBMAL1 mRNA in HepG2 cells in a REV-ERBα/β-dependent manner[1] SR9011 suppresses proliferation of the breast cancer cell lines regardless of their ER or HER2 status. SR9011 appears to pause the cell cycle of the breast cancer cells prior to M phase. Cyclin A (CCNA2) is identified as a direct target gene of REV-ERB suggesting that suppression of expression of this cyclin by SR9011 may mediate the cell cycle arrest. Treatment with SR9011 results in an increase in cells in the G0/G1 phase and a decrease of cells in S and G2/M phase suggesting that activation of REV-ERB may be resulting in decreased transition from G1 to S phase and/or from S to G2/M phase[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
SR9011 displays reasonable plasma exposure, thus, the expression of REV-ERB responsive genes is examined in the liver of mice treated with various doses of SR9011 for 6-days. The plasminogen activator inhibitor type 1 gene (Serpine1) is a REV-ERB target gene and displays dose-dependent suppression of expression in response to SR9011. The cholesterol 7α-hydroxylase (Cyp7a1) and sterol response element binding protein (Srepf1) genes have also been shown to be responsive to REV-ERB and are dose-dependently suppressed with increasing amounts of SR9011. After 12 days in D:D conditions mice are injected with a single dose of SR9011 or vehicle at CT6 (peak expression of Rev-erbα). Vehicle injection causes no disruption in circadian locomotor activity. However, administration of a single dose of SR9011 results in loss of locomotor activity during the subject dark phase. Normal activity returns the next circadian cycle, consistent with clearance of the drugs in less than 24h. The SR9011-dependent decrease in wheel running behavior in the mice under constant darkness conditions is dose-dependent and that the potency (ED50=56 mg/kg) is similar to the potency of SR9011-mediated suppression of a REV-ERB responsive gene, Srebf1 , in vivo (ED50=67mg/kg)[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
479.04
Formula
C23H31ClN4O3S
CAS 号
1379686-29-9
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Solt LA, et al. Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists. Nature. 2012 Mar 29;485(7396):62-8.
[2]. Wang Y, et al. Anti-proliferative actions of a synthetic REV-ERBα/β agonist in breast cancer cells. Biochem Pharmacol. 2015 Aug 15;96(4):315-22.
Cell Assay [2]
MCF10A, MDA-MB-231, MCF-7, MDA-MB-361, SKBR3, BT474 cells are plated in 6-well plates one day before treatment. The MTT cell proliferation assays are performed. Briefly, 3×103 to 5 × 103 cells per well are plated in 96-well plates. Twenty-four hours later, cells are treated with SR9011 (0, 2, 4, 6, 8 and 10 μM) or DMSO. Seventy-two hours after treatment, the cells are labeled with 1.2 mM MTT and incubated for 4 hours. DMSO is then added and readings are taken on a plate reader at 540 nm[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration [1]
Mice[1] For circadian gene expression experiments male C57BL6 mice (8-10 weeks of age) are either maintained on a L:D (12h:12h) cycle or on constant darkness. At circadian time (CT) 0 animals are administered a single dose of 100 mg/kg SR9011 (i.p.) and groups of animals (n=6) are sacrificed at CT0, CT6, CT12 and CT18. Gene expression is determined by real time QPCR.
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Solt LA, et al. Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists. Nature. 2012 Mar 29;485(7396):62-8.
[2]. Wang Y, et al. Anti-proliferative actions of a synthetic REV-ERBα/β agonist in breast cancer cells. Biochem Pharmacol. 2015 Aug 15;96(4):315-22.
SR-717 free acid is a non-nucleotide STING agonist with EC50s of 2.1 μM and 2.2 μM in ISG-THP1 (WT) and ISG-THP1 cGAS KO (cGAS KO) cell lines, respectively. SR-717 free acid is a stable cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) mimetic. Antitumor activity[1].
体外研究 (In Vitro)
SR-717 activates STING by inducing the same closed conformation, which thereby provides an avenue to explore this class of systemic STING agonist in diverse contexts, including antitumor immunity[1]. SR-717 (3.8 μM) induces the expression of PD-L1 in THP1 cells and in primary human peripheral blood mononuclear cells in a STING-dependent manner[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
SR-717 (30 mg/kg intraperitoneal once-per-day for 1 week) shows antitumor activities in WT or Stinggt/gt mice[1]. SR-717 (30 mg/kg intraperitoneally for 7 days) displays antitumor activity; promots the activation of CD8+ T, natural killer, and dendritic cells in relevant tissues; and facilitates antigen cross-priming[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
WT or Stinggt/gt mice[1]
Dosage:
30 mg/kg
Administration:
Intraperitoneally; once-per-day for 1 week
Result:
Maximally inhibited tumor growth.
分子量
345.26
Formula
C15H9F2N5O3
CAS 号
2375420-34-9
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Emily N Chin, et al. Antitumor activity of a systemic STING-activating non-nucleotide cGAMP mimetic. Science. 2020 Aug 21;369(6506):993-999.
Rimonabant Hydrochloride (SR 141716A Hydrochloride) is a highly potent and selective central cannabinoid receptor (CB1) antagonist with an Ki of 1.8 nM. Rimonabant Hydrochloride (SR 141716A Hydrochloride) also inhibits Mycobacterial membrane protein Large 3 (MMPL3).
IC50 & Target[1]
CB1
1.8 nM (Ki)
体外研究 (In Vitro)
Rimonabant could inhibit the growth of Mtb with an MIC of 54 μM. MmpL3, an anti-TB target, is the direct target of rimonabant[2]. Rimonabant itself (10-12-10-3 M, 12 concentrations) inhibits the basal binding of [35S]GTPgS to human cortical membranes in a concentration dependent manner, with a -log IC50 of 4.7±0.2 (IC50 = 20 μM) and a maximal inhibition of 48±2%[3].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
Rimonabant (10 mg/kg by gavage) is fed for 2 weeks to 3-month-old male obese Zucker rats as an impaired glucose tolerance model and for 10 weeks to 6-month-old male obese Zucker rats as a model of the metabolic syndrome. RANTES and MCP-1 serum levels are increased in obese vs lean Zucker rats and significantly reduced by long-term treatment with Rimonabant, which slowes weight gain in rats with the metabolic syndrome. Neutrophils and monocytes are significantly increased in young and old obese vs lean Zucker rats and lowered by Rimonabant. Platelet-bound fibrinogen is significantly enhanced in obese vs lean Zucker rats of both age, and is reduced by Rimonabant [1]. Rimonabant (20 mg daily) exhibits a significant reduction in many cardiometabolic risk factors[4].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
分子量
500.25
Formula
C22H22Cl4N4O
CAS 号
158681-13-1
中文名称
盐酸利莫那班
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Seely KA, et al. AM-251 and rimonabant act as direct antagonists at mu-opioid receptors: Implications for opioid/cannabinoid interaction studies. Neuropharmacology. 2012 Oct;63(5):905-15.
[2]. Zhang B, et al. Crystal Structures of Membrane Transporter MmpL3, an Anti-TB Drug Target. Cell. 2019 Jan 24;176(3):636-648.e13.
[3]. Erdozain, A. M. et al. The inverse agonist effect of rimonabant on G protein activation is not mediated by the cannabinoid CB1 receptor: Evidence from postmortem human brain Biochemical Pharmacology (2012), 83(2), 260-268.
[4]. Erdozain, A. M. et al. The inverse agonist effect of rimonabant on G protein activation is not mediated by the cannabinoid CB1 receptor: Evidence from postmortem human brain Biochemical Pharmacology (2012), 83(2), 260-268.
Animal Administration
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Seely KA, et al. AM-251 and rimonabant act as direct antagonists at mu-opioid receptors: Implications for opioid/cannabinoid interaction studies. Neuropharmacology. 2012 Oct;63(5):905-15.
[2]. Zhang B, et al. Crystal Structures of Membrane Transporter MmpL3, an Anti-TB Drug Target. Cell. 2019 Jan 24;176(3):636-648.e13.
[3]. Erdozain, A. M. et al. The inverse agonist effect of rimonabant on G protein activation is not mediated by the cannabinoid CB1 receptor: Evidence from postmortem human brain Biochemical Pharmacology (2012), 83(2), 260-268.
[4]. Erdozain, A. M. et al. The inverse agonist effect of rimonabant on G protein activation is not mediated by the cannabinoid CB1 receptor: Evidence from postmortem human brain Biochemical Pharmacology (2012), 83(2), 260-268.
Tirapazamine is an anticancer agent that shows selective cytotoxicity for hypoxic cells in solid tumors, thereby inducing single-and double-strand breaks in DNA, base damage, and cell death.
Clinical Trial
分子量
178.15
Formula
C7H6N4O2
CAS 号
27314-97-2
中文名称
替拉扎明
运输条件
Room temperature in continental US; may vary elsewhere.
将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
*以上所有助溶剂都可在 上海金畔生物科技有限公司 网站选购。
参考文献
[1]. Cai TY, et al. Tirapazamine sensitizes hepatocellular carcinoma cells to topoisomerase I inhibitors via cooperative modulation of hypoxia-inducible factor-1α. Mol Cancer Ther. 2014 Mar;13(3):630-42.
[2]. Sliwinska J, et al. Tirapazamine-doxorubicin interaction referring to heart oxidative stress and Ca2? balance protein levels. Oxid Med Cell Longev. 2012;2012:890826.
SR1078 is a selective agonist of retinoic acid receptor-related orphan receptor α/γ (RORα/RORγ). SR1078 directly binds to the ligand binding domain of RORα and RORγ and increases the transcriptional activity of these receptors, leading to stimulation of RORα/γ target gene transcription[1][2].
IC50 & Target
RORα/γ[1]
体外研究 (In Vitro)
SR1078 is a synthetic RORα/RORγ ligand. SR1078 modulates the conformation of RORγ in a biochemical assay and activates RORα and RORγ driven transcription. Furthermore, SR1078 stimulates expression of endogenous ROR target genes in HepG2 cells that express both RORα and RORγ. In a cell-based chimeric receptor Gal4 DNA-binding domain-NR ligand binding domain cotransfection assay, SR1078 significantly inhibits the constitutive transactivation activity of RORα and RORγ, but has no effect on the activity of FXR, LXRα and LXRβ. In a RORα cotransfection assay, treatment of cells with SR1078 (10 μM) results in a significant increase in transcription. Similarly, in the RORγ cotransfection assay, SR1078 treatment results in a stimulation of RORγ-dependent transcription activity[1]. SR1078 (2-10 μM; 24 hours) shows a dose-dependent increase in expression of A2BP1, CYP19A1, NLGN1, and IPTR1 in SH-SY5Y cells. EC50’s are in the range of 3-5 μM[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
The pharmacokinetic properties of SR1078 are examined in mice and noted significant exposure. Plasma concentrations reach 3.6 μM 1h after a 10 mg/kg i.p. injection of SR1078 and sustained levels of above 800 nM even 8h after the single injection. These levels are sufficient to perform a proof-of-principle experiment to determine if SR1078 treatment would stimulate ROR target gene expression in an animal model. Mice are treated with SR1078 (10 mg/kg; i.p.) and 2h after the injection the livers are harvested and mRNA purified for assessment of G6Pase and FGF21 gene expression.T he expression of both FGF21 and G6Pase is significantly stimulated by SR1078 treatment vs. vehicle control[1]. SR1078 (10 mg/kg; i.p.) shows a significant 25% reduction in repetitive grooming behavior in the BTBR mice[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
431.25
Formula
C17H10F9NO2
CAS 号
1246525-60-9
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Wang Y, et al. Identification of SR1078, a synthetic agonist for the orphan nuclear receptors RORα and RORγ. ACS Chem Biol. 2010 Nov 19;5(11):1029-34.
[2]. Wang Y, Billon C, Walker JK, Burris TP. Therapeutic Effect of a Synthetic RORα/γ Agonist in an Animal Model of Autism. ACS Chem Neurosci. 2016;7(2):143-148.
Kinase Assay [1]
The ALPHA screen assays are performed. Assays are performed in triplicate in white opaque 384-well plates under green light conditions (<100 lux) at room temperature. the final assay volume is 20 μl. all dilutions are made in buffer (100 mm nacl, 25 hepes, 0.1% (w>[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Assay [1]
HEK293 cells are maintained in Dulbecco’s modified Eagle’s medium (DMEM) supplemented with 10% (v/v) fetal bovine serum at 37°C under 5% CO2. HepG2 cells are maintained and routinely propagated in minimum essential medium supplemented with 10% (v/v) fetal bovine serum at 37°C under 5% CO2. In experiments where lipids and sterols are depleted, cells are maintained on charcoal treated serum (10% (v/v) fetal bovine serum) and treated with 7.5 μM lovastatin and 100 μM mevalonic acid. 24 h prior to transfection, HepG2 or HEK293 cells are plated in 96-well plates at a density of 15×103 cells/well. Transfections are performed using LipofectamineTM 2000. 16 h post-transfection, the cells are treated with vehicle or SR1078. 24 h post-treatment, the luciferase activity is measured using the Dual-GloTM luciferase assay system. The experiments are repeated at least three times[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration [1]
Mice[1] Plasma levels of SR1078 are evaluated in C57BL6 mice (n=3 per time point) administered by i.p. injection. After 1, 2, 4, and 8h blood is taken. In the 2h time point liver is taken for target gene analysis. Plasma is generated using standard centrifugation techniques, and the plasma and tissues are frozen at −80°C. Plasma and tissues are mixed with acetonitrile (1:5 (v/v) or 1:5 (w/v), respectively), sonicated with a probe tip sonicator, and analyzed for drug levels by liquid chromatography/tandem mass spectrometry.
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Wang Y, et al. Identification of SR1078, a synthetic agonist for the orphan nuclear receptors RORα and RORγ. ACS Chem Biol. 2010 Nov 19;5(11):1029-34.
[2]. Wang Y, Billon C, Walker JK, Burris TP. Therapeutic Effect of a Synthetic RORα/γ Agonist in an Animal Model of Autism. ACS Chem Neurosci. 2016;7(2):143-148.
SR7826 is a class of bis-aryl urea derived potent, selective and orally active LIM kinase (LIMK) inhibitor with an IC50 of 43 nM for LIMK1. SR7826 is >100-fold more selective for LIMK1 than ROCK and JNK kinases[1].
IC50 & Target
LIMK1
43 nM (IC50)
ROCKI
5536 nM (IC50)
ROCKII
6565 nM (IC50)
体外研究 (In Vitro)
In the profiling against a panel of 61 kinases, SR7826 (compound 18b) at 1 μM inhibits only Limk1 and STK16 with ≥80% inhibition. SR7826 is highly efficient in inhibiting cell-invasion/migration in PC-3 cells. SR7826 (compound 18b) inhibits cofilin phosphorylation in A7r5 (IC50 = 470 nM) and PC-3 cells (IC50 < 1 µM)[1]. SR7826 (1 μM) inhibits contractions of prostate strips, which were induced by electrical field stimulation and inhibits cofilin phosphorylation in prostate tissues and cultured stromal cells (WPMY-1). In WPMY-1 cells, SR7826 causes breakdown of actin filaments and reduced viability[3].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
SR7826 (10 mg/kg; oral gavage; once daily; for 11 days; hAPPJ20 mice) treatment significantly reduces the phosphorylation of cofilin at Ser3. SR7826 also increases both apical and basal thin spine density significantly in hAPPJ20 mice over mock-treated animals[2]. The plasma pharmacokinetics studies on rats are investigated. After intravenous injection, the PK properties of SR7826 (compound 18b; 1mg/kg) with a Cl of 5.2 mL/min/kg, a T1/2 of 2.2h, an AUC of 8.4 μM*h and a Cmax of 7.7 μM, and has 36% oral bioavailability in rats (oral administration; 2mg/kg)[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
hAPPJ20 mice (6-mouth-old)[2]
Dosage:
10 mg/kg
Administration:
Oral gavage; once daily; for 11 days
Result:
Significantly reduced the phosphorylation of cofilin at Ser3, a LIMK1 substrate.
分子量
387.43
Formula
C22H21N5O2
CAS 号
1219728-20-7
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Powder
-20°C
3 years
4°C
2 years
In solvent
-80°C
6 months
-20°C
1 month
参考文献
[1]. Yan Yin, et al. Bis-aryl urea derivatives as potent and selective LIM kinase (Limk) inhibitors. J Med Chem. 2015 Feb 26;58(4):1846-61.
[2]. Benjamin W Henderson, et al. Pharmacologic inhibition of LIMK1 provides dendritic spine resilience against β-amyloid. Sci Signal. 2019 Jun 25;12(587):eaaw9318.
[3]. Qingfeng Yu, et al. Inhibition of human prostate smooth muscle contraction by the LIM kinase inhibitors, SR7826 and LIMKi3. Br J Pharmacol. 2018 Jun;175(11):2077-2096.
SR-1114 is a first-in-class PROTAC ENL degrader. SR-1114 elicits rapid, CRBN-dependent degradation of ENL with DC50s of 150 nM, 311 nM, and 1.65 μM in MV4;11 , MOLM-13, and OCI/AML-2 cells, respectively[1].
IC50 & Target[1]
Cereblon
分子量
830.86
Formula
C39H42N8O11S
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Leopold Garnar-Wortzel, et al. Chemical Inhibition of ENL/AF9 YEATS Domains in Acute Leukemia. ACS Cent Sci. 2021 May 26;7(5):815-830.
