Isosilybin A 是一种从 silymarin 中分离出来的黄酮木脂素,具有抗前列腺癌 (PCA) 活性。Isosilybin A 抑制癌细胞增殖并诱导 G1 期停滞和凋亡,通过靶向 Akt-NF-κB-androgen receptor (AR) 轴激活前列腺癌细胞的凋亡机制。
Isosilybin A Chemical Structure
CAS No. : 142796-21-2
规格
价格
是否有货
数量
10 mM * 1 mL in DMSO
¥3715
询价
1 mg
¥2000
In-stock
5 mg
¥3500
询价
10 mg
询价
50 mg
询价
* Please select Quantity before adding items.
生物活性
Isosilybin A, a flavonolignan isolated from silymarin, has anti-prostate cancer (PCA) activity. Isosilybin A inhibits proliferation and induces G1 phase arrest and apoptosis in cancer cells, which activates apoptotic machinery in PCA cells via targeting Akt-NF-κB-androgen receptor (AR) axis[1][2].
分子量
482.44
Formula
C25H22O10
CAS 号
142796-21-2
中文名称
异水飞蓟宾A
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Deep G, et al. Isosilybin B and isosilybin A inhibit growth, induce G1 arrest and cause apoptosis in human prostatecancer LNCaP and 22Rv1 cells. Carcinogenesis. 2007 Jul;28(7):1533-42.
[2]. Deep G, et al. Isosilybin A induces apoptosis in human prostate cancer cells via targeting Akt, NF-κB, and androgen receptor signaling. Mol Carcinog. 2010 Oct;49(10):902-12.
Ki8751 is a potent VEGFR2 inhibitor with an IC50 of 0.9 nM.
IC50 & Target
VEGFR2
0.9 nM (IC50)
体外研究 (In Vitro)
Ki8751 inhibits VEGFR-2 phosphorylation at an IC50 value of 0.90 nM, and also inhibits the PDGFR family members such as PDGFRR and c-Kit at 67 nM and 40 nM, respectively. However, Ki8751 does not have any inhibitory activity against other kinases such as EGFR, HGFR, InsulinR and others even at 10000 nM. Ki8751 suppresses the growth of the VEGF-stimulated human umbilical vein endothelial cell (HUVEC) on a nanomolar level[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)
Ki8751 shows significant antitumor activity against five human tumor xenografts such as GL07 (glioma), St-4 (stomach carcinoma), LC6 (lung carcinoma), DLD-1 (colon carcinoma) and A375 (melanoma) in nude mice and also shows complete tumor growth inhibition with the LC-6 xenograft in nude rats following oral administration once a day for 14 days at 5 mg/kg without any body weight loss[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
469.41
Formula
C24H18F3N3O4
CAS 号
228559-41-9
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Kubo K, et al. Novel potent orally active selective VEGFR-2 tyrosine kinase inhibitors: synthesis, structure-activity relationships, and antitumor activities of N-phenyl-N’-{4-(4-quinolyloxy)phenyl}ureas. J Med Chem, 2005, 48(5), 1359-1366.
Kinase Assay [1]
VEGFR-2 kinase assay is described below; GST-fusion proteins of KDR (Flk-1: cytoplasmic domain) are produced in the baculo-virus expression system. GST-KDR is premixed with a serial dilution of Ki8751 in the kinase buffer. The kinase reaction is initiated by the addition of 2 µM ATP in a solution of MnCl2. After 20 min incubation at room temperature, the reaction is stopped with an addition of EDTA. Phosphorylation levels of GST-KDR are detected by immunoblotting with anti-phosphotyrosine monoclonal antibodies (PY20) and detected by ECL fluorography[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]
HUVECs are placed at a density of 4000 cells/200 µL/well on collagene type I precoated 96-well plates in M199 medium with 5% fetal bovine serum (FBS). After 24 h, the cells are incubated for 1 h in the presence or absence of Ki8751; then the cells are stimulated by rhVEGF (20 ng/mL). The cultures are incubated at 37 °C for 72 h, then pulsed with 1 µCi/well [3H]thymidine and reincubated for 14 h. Cells are assayed for the incorporation of tritium using a beta counter[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: The effects of Ki8751 on tumor growth is tested against various tumors, human stomach carcinoma (St-4), human lung carcinoma (LC-6), human colon carcinoma (DLD-1) and human melanoma (A375), using human tumor xenografts in nude mice. Ki8751 is administered orally to mice in the experimental groups once a day for 9 consecutive days at 5 mg/kg, and the vehicle is administered to control animals. Tumor volumes are monitored twice weekly[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]. Kubo K, et al. Novel potent orally active selective VEGFR-2 tyrosine kinase inhibitors: synthesis, structure-activity relationships, and antitumor activities of N-phenyl-N’-{4-(4-quinolyloxy)phenyl}ureas. J Med Chem, 2005, 48(5), 1359-1366.
GSK484 hydrochloride is a selective and reversible peptidylarginine deiminase 4 (PAD4) inhibitor. GSK484 hydrochloride demonstrates high affinity binding to PAD4 with IC50s of 50 nM in the absence of Calcium. In the presence of 2 mM Calcium, notably lower potency (250 nM) is observed.
IC50 & Target
IC50: 50 nM (PAD4, in the absence of Calcium), 250 nM (PAD4, in the presence of 2 mM Calcium)[1]
体外研究 (In Vitro)
GSK484 demonstrates high affinity binding to the low-calcium form of PAD4 with IC50s of 50 nM and 250 nM in the absence of Calcium (0 mM) and Calcium (2 mM), respectively. GSK484 also inhibits PAD4 citrullination (at 0.2 mM Calcium) of benzoyl-arginine ethyl ester (BAEE) substrate in a concentration-dependent manner, as detected using an NH3 release assay[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)
To address whether PAD4 inhibition can suppress cancer-associated kidney injury, MMTV-PyMT mice are treated with the PAD4 inhibitor GSK484 at 4 mg/kg daily for one week. This dose suppress the elevated number of neutrophils undergoing NETosis in peripheral blood in mice with cancer. In parallel, the total protein level in urine from MMTV-PyMT mice is significantly reduced compared with untreated tumor-bearing mice, further supporting an improved functional status of the kidneys after GSK484 treatment. Administration of GSK484 at a dose of 4 mg/kg daily during one week reverts signs of kidney dysfunction in tumor-bearing mice to the same extent as DNase I treatment, without any detectable signs of toxicity[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
510.03
Formula
C27H32ClN5O3
CAS 号
1652591-81-5
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Lewis HD, et al. Inhibition of PAD4 activity is sufficient to disrupt mouse and human NET formation. Nat Chem Biol. 2015 Mar;11(3):189-91.
[2]. Cedervall J, et al. Pharmacological targeting of peptidylarginine deiminase 4 prevents cancer-associated kidney injury in mice. Oncoimmunology. 2017 Apr 20;6(8):e1320009.
Kinase Assay [1]
PAD4 is serially diluted in the presence of 10 nM GSK215 in assay buffer (100 mM HEPES, pH 8, 50 mM NaCl, 5% glycerol, 1 mM CHAPS, 1 mM DTT) at varying concentrations of calcium (0, 0.2, 2 and 10 mM). Following incubation for 50 min, apparent Kds for each calcium concentration are determined using a single site saturation curve. For IC50 determination, test compounds (e.g., GSK484) are serially diluted in DMSO (1% final assay concentration) and tested at the same range of calcium concentrations in the presence of PAD4 (at the calculated Kd for each calcium condition) and 10 nM GSK215 in the same assay buffer and volume. Reactions are incubated for 50 min after which IC50 values are calculated using a four-parameter logistic equation[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 stably expressing N-terminal FLAG-tagged PAD1, PAD2, PAD3 or PAD4 are engineered by retroviral transduction. Cells are grown in 15 cm diameter plates to subconfluency in DMEM supplemented with 10% Foetal Bovine Serum, harvested by centrifugation and washed once in PBS/2 mM EGTA. Cells are lysed in 50 mM Tris-Cl, pH 7.4, 1.5 mM MgCl2, 5% glycerol, 150 mM NaCl, 25 mM NaF, 1 mM Na3VO4, 0.4% NP40, 1 mM DTT with protease inhibitors. Lysates are pre-incubated for 20 min at 4°C with DMSO alone (2%), 100 µM of GSK199, GSK484, GSK106 or 200 µM Cl-amidine. Citrullination reactions are performed for 30 min at 37°C in the presence of 2 mM calcium. Extracts are loaded on to gels, proteins separated by SDS-PAGE and transferred to PVDF membranes. Citrullinated proteins are then chemically modified and detected using anti-modified citrulline antibody. FLAG-PAD constructs are detected using anti-FLAG antibody[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]
Mice[2] The study includes two transgenic mouse models, the MMTV-PyMT mouse model for mammary carcinoma (FVB/n background) and the RIP1-Tag2 mouse model for pancreatic neuroendocrine carcinoma (C57BL/6 background). Mice are treated daily by intra-peritoneal injections of the PAD4 inhibitor GSK484 (4 mg/kg). GSK484 is dissolved in 99.9% ethanol at a concentration of 25 mg/mL to generate a stock solution and further diluted 1:50 in 0.9% NaCl shortly before injection of 200 μL/mouse[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]. Lewis HD, et al. Inhibition of PAD4 activity is sufficient to disrupt mouse and human NET formation. Nat Chem Biol. 2015 Mar;11(3):189-91.
[2]. Cedervall J, et al. Pharmacological targeting of peptidylarginine deiminase 4 prevents cancer-associated kidney injury in mice. Oncoimmunology. 2017 Apr 20;6(8):e1320009.
The Mini Roller is used for liquid mixing, cell cultures, hybridization, and more. It can operate on the benchtop or in dry or humid incubators . Rollers can be added for a total of up to 11, and the distance between them adjusted by adding or removing rollers to accommodate different sizes of tubes,bottles or other containers.
Silybin B 是从 Silybum marianum 中分离出的一种黄酮木脂素,具有抗肿瘤活性。Silybin B 是水飞蓟素最有效的抗纤维原性和抗低聚物成分,是一种有前景的抗阿尔茨海默病药物候选。
Silybin B Chemical Structure
CAS No. : 142797-34-0
规格
价格
是否有货
数量
1 mg
¥2000
In-stock
5 mg
¥4000
询价
10 mg
询价
50 mg
询价
* Please select Quantity before adding items.
生物活性
Silybin B, a flavonolignan separated from Silybum marianum, has anti-tumor activity. Silybin B is the most potent antifibrillogenic and anti-oligomeric component of silymarin and proposes it as a promising anti Alzheimer’s disease drug candidate[1][2].
分子量
482.44
Formula
C25H22O10
CAS 号
142797-34-0
中文名称
水飞蓟宾B
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]. An-Shen Lin, et al. Cancer Preventive Agents. 7. Antitumor-Promoting Effects of Seven Active Flavonolignans from Milk Thistle (Silybum marianum.) on Epstein-Barr Virus Activation, Pharmaceutical Biology, 45:10, 735-738.
[2]. Sciacca MFM, et al. Inhibition of Aβ Amyloid Growth and Toxicity by Silybins: The Crucial Role of Stereochemistry. ACS Chem Neurosci. 2017 Aug 16;8(8):1767-1778.
Vinpocetine (Ethyl apovincaminate) is a derivative of the alkaloid Vincamine that blocks voltage-gated Na+ channels. The IC50 value of Vinpocetine on direct IKK inhibition in the cell-free system is 17.17 μM. Vinpocetine is a phosphodiesterase (PDE) inhibitor and inhibits NF-κB-dependent inflammatory responses by directly targeting IκB kinase complex (IKK), and has been widely used for the treatment of cerebrovascular disorders[1][2][3].
IC50 & Target
IKK
17.17 μM (IC50)
体外研究 (In Vitro)
Vinpocetine (5-50 μM; 7 hours; VSMCs, HUVECs, A549 cells and RAW264.7 cells) potently inhibits TNF-α-induced NF-κB-dependent transcriptional activity in a dose-dependent manner with an approximate IC50 value of 25 μM. Vinpocetine do not have a significant effect on cell viability[1]. Vinpocetine (50 μM; 7 hours; VSMCs, HUVECs, A549 cells and RAW264.7 cells) potently inhibits TNF-α-induced up-regulation of TNF-α, IL-1β, IL-8, MCP-1, VCAM-1, ICAM-1and MIP-2 transcripts in several cell types[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.
RT-PCR[1]
Cell Line:
VSMCs, HUVECs, A549 cells and RAW264.7 cells
Concentration:
50 μM
Incubation Time:
7 hours
Result:
Inhibited TNF-α-induced up-regulation of TNF-α, IL-1β, IL-8, MCP-1, VCAM-1, ICAM-1and MIP-2 transcripts in several cell types.
体内研究 (In Vivo)
Vinpocetine (2.5-10 mg/kg; intraperitoneal injection; C57BL/6 mice) potently inhibits TNF-α- or LPS-induced up-regulation of proinflammatory mediators, including TNF-α, IL-1β, and MIP-2, and decreases interstitial infiltration of polymorphonuclear leukocytes in a mouse model of TNF-α- or LPS-induced lung inflammation[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:
C57BL/6 mice (8 weeks of age)[1]
Dosage:
2.5 mg/kg, 5 mg/kg, and 10 mg/kg
Administration:
Intraperitoneal injection
Result:
Inhibited TNF-α- or LPS-induced up-regulation of proinflammatory mediators, including TNF-α, IL-1β, and MIP-2, and decreased interstitial infiltration of polymorphonuclear leukocytes in a mouse model of TNF-α- or LPS-induced lung inflammation.
Clinical Trial
分子量
350.45
Formula
C22H26N2O2
CAS 号
42971-09-5
中文名称
长春西汀;长春西丁;长春乙酯;卡兰;阿扑长春胺酸乙酯;长春酸乙酯
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Kye-Im Jeon et al. Vinpocetine inhibits NF-κB-dependent inflammation via an IKK-dependent but PDE-independent mechanism PNAS May 25, 2010 vol. 107 no. 21 9795-9800
[2]. Patyar S, et al. Role of vinpocetine in cerebrovascular diseases. Pharmacol Rep. 2011;63(3):618-28.
[3]. Alexandre E. Medina Vinpocetine as a potent antiinflammatory agent PNAS June 1, 2010, Vol. 107, No. 22 9921-9922.
GANT 61 is an inhibitor of Gli1 and Gli2 targeting the Hedgehog/GLI pathway.
IC50 & Target
Gli1/2[1]
体外研究 (In Vitro)
GANT61 (20 μM) induces greater cell death than targeting Smo (cyclopamine). GANT61 (0, 5, 10, 20 μM) inhibits clonogenic survival of human colon carcinoma cell lines. GANT61 (20 μM, 0-72 hr) down-regulates Gli1 and Gli2 expression in HT29 cells. GANT61 (0, 10 μM or 20 μM) differentially regulates genes involved in the balance between cell death and cell survival[1]. GANT-61 inhibits cell viability and induces apoptosis in pancreatic CSCs. GANT-61 inhibits expression of downstream targets of Shh pathway, decreases Gli-DNA interaction, Gli transcriptional activity and Gli nuclear translocation in pancreatic CSCs. GANT-61 differentially regulates genes involved in cell survival, cell death and pluripotency. GANT-61 inhibits motility, invasion and migration of CSCs[2]. GANT61 sensitivity positively correlates to GLI1 and negatively to MYCN expression in the neuroblastoma cell lines tested. GANT61 downregulates GLI1, c-MYC, MYCN and Cyclin D1 expression and induces apoptosis of neuroblastoma 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)
GANT-61 (40 mg/kg, i.p., three days per week) inhibits CSC tumor growth in NOD/SCID IL2Rγ null mice[2]. GANT61 (50 mg/kg, p.o.) enhances the effects of chemotherapeutic drugs used in the treatment of neuroblastoma in an additive or synergistic manner and reduces the growth of established neuroblastoma xenografts in nude mice[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.
分子量
429.60
Formula
C27H35N5
CAS 号
500579-04-4
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:
Ethanol : 66.67 mg/mL (155.19 mM; Need ultrasonic)
Solubility: 2.5 mg/mL (5.82 mM); Suspended solution; Need ultrasonic
*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]. Mazumdar T, et al. Hedgehog signaling drives cellular survival in human colon carcinoma cells. Cancer Res. 2011 Feb 1;71(3):1092-102.
[2]. Fu J, et al. GANT-61 inhibits pancreatic cancer stem cell growth in vitro and in NOD/SCID/IL2R gamma null mice xenograft. Cancer Lett. 2013 Mar 1;330(1):22-32.
[3]. Wickstrom M, et al. Targeting the hedgehog signal transduction pathway at the level of GLI inhibits neuroblastoma cell growth in vitro and in vivo. Int J Cancer. 2013 Apr 1;132(7):1516-24.
Cell Assay [2]
Cells (1.5×104) are incubated with 0, 1, 5 and 10 μM of GANT-61 in 250 μL of culture medium in 96-well plate for 48 and 72 h. Cell viability is determined by the XTT assay. In brief, a freshly prepared XTT-PMS labeling mixture (50 μL) is added to the cell culture. The absorbance is measured at 450 nm with λ correction at 650 nm. The cell viability is expressed as ΔOD (OD450 − OD650). The apoptosis is determined by FACS analysis of propidium iodide (PI)-stained cells. In brief, cells are trypsinized, washed with PBS and resuspended in 200 μL PBS with 10 μL RNAase (10 mg/mL) and incubated at 37°C for 30 min. After incubation, 50 μL PI solution is added and cells are analyzed for apoptosis using a flow cytometry.
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]
Humanized NOD/SCID/IL2Rgammanull mice are used for the assay. Before CSC’s injection, mice are humanized with tail vein injection of human normal CD34+ peripheral blood stem/progenitor cells. CD34+peripheral blood stem/progenitor cells (500 cells/mouse, 50-75 μL volume) are injected through tail vein. After 3 days, human pancreatic CSCs (1×103 cells mixed with Matrigel, Becton Dickinson, Bedford, MA, in 75 μL total volume, 50:50 ratio) are injected subcutaneously into the flanks of NOD/SCID IL2Rγnull mice (4–6 weeks old). After two weeks of CSC implantation, mice (10 mice per group) are treated with GANT-61(0 and 40 mg/kg body weight) ip three times per week for 6 weeks. At the end of the experiment, mice are euthanized, and tumors are isolated for biochemical analysis.
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]. Mazumdar T, et al. Hedgehog signaling drives cellular survival in human colon carcinoma cells. Cancer Res. 2011 Feb 1;71(3):1092-102.
[2]. Fu J, et al. GANT-61 inhibits pancreatic cancer stem cell growth in vitro and in NOD/SCID/IL2R gamma null mice xenograft. Cancer Lett. 2013 Mar 1;330(1):22-32.
[3]. Wickstrom M, et al. Targeting the hedgehog signal transduction pathway at the level of GLI inhibits neuroblastoma cell growth in vitro and in vivo. Int J Cancer. 2013 Apr 1;132(7):1516-24.
Pimonidazole is a novel hypoxia marker for complementary study of tumor hypoxia and cell proliferation in tumor[1]. Pimonidazole accumulates in hypoxic cells via covalent binding with macromolecules or by forming reductive metabolites after reduction of its nitro group, it can be used for qualitative and quantitative assessment of tumor hypoxia [2].
体外研究 (In Vitro)
Pimonidazole, the exogenous hypoxia marker, is a 2-nitroimidazole compound, which forms covalent bonds with cellular macromolecules at oxygen levels below 1.3%. Detection: Hypoxic cells were recognized by immunohistochemical detection of pimonidazole using a mouse monoclonal antibody. Cell proliferation was detected with a commercially available monoclonal antibody for proliferating cell nuclear antigen (PCNA). Assessment of hypoxia and cell proliferation was made qualitatively with light microscopy and quantitatively using point counting and image analysis software methods.
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
分子量
254.29
Formula
C11H18N4O3
CAS 号
70132-50-2
中文名称
哌莫硝唑; 乏氧示踪剂
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Varia MA, et al. Pimonidazole: a novel hypoxia marker for complementary study of tumor hypoxia and cell proliferation in cervical carcinoma. Gynecol Oncol. 1998 Nov;71(2):270-7.
[2]. Masaki Y, et al. Imaging Mass Spectrometry Revealed the Accumulation Characteristics of the 2-Nitroimidazole-Based Agent “Pimonidazole” in Hypoxia. PLoS One. 2016 Aug 31;11(8):e0161639.
TAK-285 is a potent, selective, ATP-competitive and orally active HER2 and EGFR(HER1) inhibitor with IC50 of 17 nM and 23 nM, respectively. TAK-285 is >10-fold selectivity for HER1/2 than HER4, and less potent to MEK1/5, c-Met, Aurora B, Lck, CSK etc. TAK-285 has effective antitumor activity[1]. TAK-285 can cross the blood-brain barrier (BBB)[2].
IC50 & Target[1]
EGFR
23 nM (IC50)
HER2
17 nM (IC50)
体外研究 (In Vitro)
TAK-285 (Compound 34e) shows significant growth inhibitory activity against BT-474 cells (HER2-overexpressing human breast cancer cell line) with GI50 of 17 nM[1]. TAK-285 (Compound 34e) exhibits HER4 inhibitory activity with an IC50 value of 260 nM. TAK-285 also inhibits MEK1, MEK5, c-Met, Aurora B, Lck, CSK and Lyn B with IC50s of 1100 nM, 5700 nM, 4200 nM, 1700 nM, 2400 nM, 4700 nM and 5200 nM, respectively[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)
TAK-285 (Compound 34e; 50-100 mg/kg; oral administration; twice daily; for 14 days; female BALB/cAJcl mice) treatment exhibits dose-dependent tumor growth inhibition (tumor/control ratio [T/C]): 44% and 11% at 50 and 100 mg/kg, respectively) without significant body weight loss in 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.
Animal Model:
Female BALB/cAJcl mice (7-weeks old) with 4−1ST xenograft models[1]
Dosage:
50 mg/kg, 100 mg/kg
Administration:
Oral administration; twice daily; for 14 days
Result:
Exhibited dose-dependent tumor growth inhibition.
Clinical Trial
分子量
547.96
Formula
C26H25ClF3N5O3
CAS 号
871026-44-7
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Ishikawa T, et al. Design and synthesis of novel human epidermal growth factor receptor 2 (HER2)/epidermal growth factor receptor (EGFR) dual inhibitors bearing a pyrrolo[3,2-d]pyrimidine scaffold. J Med Chem. 2011 Dec 8;54(23):8030-50.
[2]. Erdo F, et al. Verification of brain penetration of the unbound fraction of a novel HER2/EGFR dual kinase inhibitor (TAK-285) by microdialysis in rats. Brain Res Bull. 2012 Mar 10;87(4-5):413-9.
Hydroxyurea is a cell apoptosis inducer that inhibit DNA synthesis through inhibition of ribonucleotide reductase.
体外研究 (In Vitro)
Hydroxyurea is used in a number of myeloproliferative, neoplastic, HIV, and non-hematological diseases[1]. Treatment of cells in primary culture with 30 μM hydroxyurea for 96 hours significantly increases the fractional HbF content. The Gγ: Aγ-globin mRNA is induced 0.30- to 8-fold in vitro[2]. Hydroxyurea has been shown to block HIV-1 reverse transcription and/or replication in quiescent peripheral blood mononuclear cells and macrophages[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)
Hydroxyurea therapy producs consistent reductions in WBC and ANC without improvement in anemia over 17 weeks. Hydroxyurea at 50mg/kg produces a reduced white blood cell count, absolute neutrophil count and no improvement in anemia compared to vehicle treated sickle cell mice[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
76.05
Formula
CH4N2O2
CAS 号
127-07-1
中文名称
羟基脲
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Kovacic P, et al. Hydroxyurea (therapeutics and mechanism): metabolism, carbamoyl nitroso, nitroxyl, radicals, cell signaling and clinical applications. Med Hypotheses. 2011 Jan;76(1):24-31.
[2]. Watanapokasin Y, et al. In vivo and in vitro studies of fetal hemoglobin induction by hydroxyurea in beta-thalassemia/hemoglobin E patients. Exp Hematol. 2005 Dec;33(12):1486-92.
[3]. Lori F, et al. Rationale for the use of hydroxyurea as an anti-human immunodeficiency virus drug. Clin Infect Dis. 2000 Jun;30 Suppl 2:S193-7.
[4]. Lebensburger JD, et al. Hydroxyurea therapy requires HbF induction for clinical benefit in a sickle cell mouse model. Haematologica. 2010 Sep;95(9):1599-603.
Animal Administration [4]
Mice: To determine whether hydroxyurea would improve anemia and/or prevent or diminish the development of organ damage in the absence of HbF induction, hydroxyurea, at doses of 25 mg/kg, 50 mg/kg, and 100 mg/kg, or vehicle is administered five days per week to SCD mice[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.
参考文献
[1]. Kovacic P, et al. Hydroxyurea (therapeutics and mechanism): metabolism, carbamoyl nitroso, nitroxyl, radicals, cell signaling and clinical applications. Med Hypotheses. 2011 Jan;76(1):24-31.
[2]. Watanapokasin Y, et al. In vivo and in vitro studies of fetal hemoglobin induction by hydroxyurea in beta-thalassemia/hemoglobin E patients. Exp Hematol. 2005 Dec;33(12):1486-92.
[3]. Lori F, et al. Rationale for the use of hydroxyurea as an anti-human immunodeficiency virus drug. Clin Infect Dis. 2000 Jun;30 Suppl 2:S193-7.
[4]. Lebensburger JD, et al. Hydroxyurea therapy requires HbF induction for clinical benefit in a sickle cell mouse model. Haematologica. 2010 Sep;95(9):1599-603.
The Mini Roller is used for liquid mixing, cell cultures, hybridization, and more. It can operate on the benchtop or in dry or humid incubators . Rollers can be added for a total of up to 11, and the distance between them adjusted by adding or removing rollers to accommodate different sizes of tubes,bottles or other containers.
Larotaxel (XRP9881) is a taxane analogue with preclinical activity against taxane-resistant breast cancer. Larotaxel (XRP9881) exerts its cytotoxic effect by promoting tubulin assembly and stabilizing microtubules, ultimately leading to cell death by apoptosis. It presents the ability to cross the blood brain barrier and has a much lower affinity for P-glycoprotein 1 than Docetaxel[1][2][3].
Clinical Trial
分子量
831.90
Formula
C45H53NO14
CAS 号
156294-36-9
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Diéras V, et al. Phase II multicenter study of larotaxel (XRP9881), a novel taxoid, in patients with metastatic breast cancer who previously received taxane-based therapy. Ann Oncol. 2008 Jul;19(7):1255-60.
[2]. Morris PG, et al. Novel anti-tubulin cytotoxic agents for breast cancer. Expert Rev Anticancer Ther. 2009 Feb;9(2):175-85.
[3]. Zatloukal P, et al. Randomized multicenter phase II study of larotaxel (XRP9881) in combination with cisplatin or gemcitabine as first-line chemotherapy in nonirradiable stage IIIB or stage IV non-small cell lung cancer. J Thorac Oncol. 2008 Aug;3(8):894-901.
Reparixin L-lysine salt is an allosteric inhibitor of chemokine receptor 1/2 (CXCR1/2) activation.
IC50 & Target[1][5]
CXCR1wt
5.6 nM (IC50, in L1.2 cells)
CXCR1Ile43Val
80 nM (IC50, in L1.2 cells)
CXCR1
1 nM (IC50, in cells)
CXCR2
∼100 nM (IC50, in cells)
体外研究 (In Vitro)
Reparixin is a potent functional inhibitor of CXCL8-induced biological activities on human PMNs with a marked selectivity (around 400-fold) for CXCR1, as shown in specific experiments on CXCR1/L1.2 and CXCR2/L1.2 transfected cells and on human PMNs. The efficacy of Reparixin is significantly lower in L1.2 cells expressing Ile43Val CXCR1 mutant (IC50 values of 5.6 nM and 80 nM for CXCR1 wt and CXCR1 Ile43Val, respectively)[1]. Reparixin is a non-competitive allosteric inhibitor of IL-8 receptors with a 400-fold higher efficacy in inhibiting CXCR1 activity than CXCR2[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 pharmacokinetics and metabolism of Reparixin are investigated in rats and dogs after intravenous administration of [14C]-Reparixin L-lysine salt. Plasma protein binding of Reparixin is >99% in the laboratory animals and humans up to 50 µg/mL, but lower at higher concentrations. Although radioactivity is rapidly distributed into rat tissues, Vss is low (about 0.15 L/kg) in both rat and dog. Nevertheless, Reparixin is more rapidly eliminated in rats (t1/2~0.5 h) than in dogs (t1/2~10 h)[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.
Clinical Trial
分子量
429.57
Formula
C20H35N3O5S
CAS 号
266359-93-7
中文名称
瑞帕利辛L-赖氨酸盐
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Moriconi A, et al. Design of noncompetitive interleukin-8 inhibitors acting on CXCR1 and CXCR2. J Med Chem. 2007 Aug 23;50(17):3984-4002.
[2]. Bertini R, et al. Receptor binding mode and pharmacological characterization of a potent and selective dual CXCR1/CXCR2non-competitive allosteric inhibitor. Br J Pharmacol. 2012 Jan;165(2):436-54.
[3]. Midgley I, et al. Species differences in the pharmacokinetics and metabolism of reparixin in rat and dog. Xenobiotica. 2006 May;36(5):419-40
[4]. Catrina, Anca, et al. METHODS AND COMPOUNDS FOR THE TREATMENT OF BONE LOSS AND/OR PAIN. US 20170105971 A1.
[5]. Bertini R, et al. Noncompetitive allosteric inhibitors of the inflammatory chemokine receptors CXCR1 and CXCR2: prevention of reperfusion injury. Proc Natl Acad Sci U S A. 2004 Aug 10;101(32):11791-6.
Cell Assay [1]
L1.2 Cell suspension (1.5-3×106 cells/mL) is incubated at 37°C for 15 min in the presence of vehicle or of Reparixin (1 nM-1 μM) and next seeded in triplicates in the upper compartment of the chemotactic chamber. Different agonists are seeded in the lower compartment of the chamber at the following concentrations: 1 nM CXCL8, 0.03 nM fMLP, 10 nM CXCL1, 2.5 nM CCL2, 30 nM C5a. The chemotactic chamber is incubated at 37°C in air with 5% CO2 for 45 min (human PMNs) or 2 h (monocytes). At the end of incubation, the filter is removed, fixed, and stained and five oil immersion fields at high magnification (100×) are counted for each migration well after sample coding. L1.2 migration is evaluated using 5 μm pore size Transwell filters[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 [3]
Rats and Dogs[3] Male and female Sprague-Dawley CD (albino) rats and male Lister Hooded (partially pigmented) rats are used. Male and female beagle Dogs (age about 15 months, bodyweight range 8.3-9.4 kg at the time of dosing) are used. Rats and Dogs are dosed i.v. with repurified [14C]-Reparixin free acid and an equivalent quantity of L-lysine suitably radiodiluted with Reparixin L-lysine salt in a solution of sterile isotonic (0.9%, w/v) saline. Rats are dosed with a solution of total drug concentration 9 mg/mL at a dose volume of 5 mL/kg (30 mg free Reparixin /kg) by bolus injection into a caudal vein. Dogs are dosed with a solution of total drug concentration 100 mg/mL at a dose volume of 0.5 mL/kg (33 mg free Reparixin/kg) by bolus injection into a superficial forelimb vein.
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]. Moriconi A, et al. Design of noncompetitive interleukin-8 inhibitors acting on CXCR1 and CXCR2. J Med Chem. 2007 Aug 23;50(17):3984-4002.
[2]. Bertini R, et al. Receptor binding mode and pharmacological characterization of a potent and selective dual CXCR1/CXCR2non-competitive allosteric inhibitor. Br J Pharmacol. 2012 Jan;165(2):436-54.
[3]. Midgley I, et al. Species differences in the pharmacokinetics and metabolism of reparixin in rat and dog. Xenobiotica. 2006 May;36(5):419-40
[4]. Catrina, Anca, et al. METHODS AND COMPOUNDS FOR THE TREATMENT OF BONE LOSS AND/OR PAIN. US 20170105971 A1.
[5]. Bertini R, et al. Noncompetitive allosteric inhibitors of the inflammatory chemokine receptors CXCR1 and CXCR2: prevention of reperfusion injury. Proc Natl Acad Sci U S A. 2004 Aug 10;101(32):11791-6.
Abemaciclib methanesulfonate (LY2835219 methanesulfonate) is a selective CDK4/6 inhibitor with IC50s of 2 nM and 10 nM for CDK4 and CDK6, respectively[1][2][3].
IC50 & Target[3]
Cdk4/cyclin D1
2 nM (IC50)
CDK6/cyclinD1
10 nM (IC50)
CDK2/cyclinE
504 nM (IC50)
CDK9/cyclinT1
57 nM (IC50)
CDK1/cyclinB1
1627 nM (IC50)
CDK7/Mat1/cyclinH1
3910 nM (IC50)
Cdk5/p25
355 nM (IC50)
CDK5/p35
287 nM (IC50)
PIM1
50 nM (IC50)
PIM2
3400 nM (IC50)
HIPK2
31 nM (IC50)
DYRK2
61 nM (IC50)
CK2
117 nM (IC50)
GSK3b
192 nM (IC50)
JNK3
389 nM (IC50)
FLT3 (D835Y)
403 nM (IC50)
FLT3
3960 nM (IC50)
DRAK1
659 nM (IC50)
体外研究 (In Vitro)
Abemaciclib (LY2835219) reduces cell viability with the IC50 values ranging from 0.5 μM to 0.7 μM, inhibits Akt and ERK signaling but not mTOR activation at head and neck squamous cell carcinoma (HNSCC) cells[1]. Abemaciclib (LY2835219) shows inhibition on A375R1-4, M14R, and SH4R with EC50 values ranging from 0.3 to 0.6 μM; Abemaciclib inhibits the proliferation of the parental A375 and resistant A375RV1 and A375RV2 cells with similar potencies with IC50 values of 395, 260, and 463 nM, respectively[2]. Abemaciclib (LY2835219) inhibits CDK4 and CDK6 with low nanomolar potency, inhibits Rb phosphorylation resulting in a G1 arrest and inhibition of proliferation, and its activity is specific for Rb-proficient 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)
Abemaciclib (LY2835219) (45 mg/kg, p.o.) in combination with RAD001 causes a cooperative antitumor effect in HNSCC xenograft tumor[1]. Abemaciclib (LY2835219) (45 or 90 mg/kg, p.o.) shows significant tumor growth inhibition in an A375 xenograft model[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
602.70
Formula
C28H36F2N8O3S
CAS 号
1231930-82-7
运输条件
Room temperature in continental US; may vary elsewhere.
Solubility: 2 mg/mL (3.32 mM); Suspended solution; Need ultrasonic
7.
请依序添加每种溶剂: 5% DMSO 95% (20% SBE-β-CD in saline)
Solubility: ≥ 2 mg/mL (3.32 mM); Clear solution
*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]. Ku BM, et al. The CDK4/6 inhibitor LY2835219 has potent activity in combination with mTOR inhibitor in head and neck squamous cell carcinoma. Oncotarget. 2016 Mar 22;7(12):14803-13.
[2]. Yadav V, et al. The CDK4/6 inhibitor LY2835219 overcomes PLX4032 resistance resulting from MAPK reactivation and cyclin D1 upregulation. Mol Cancer Ther. 2014 Oct;13(10):2253-63.
[3]. Gelbert LM, et al. Preclinical characterization of the CDK4/6 inhibitor LY2835219: in-vivo cell cycle-dependent/independent anti-tumor activities alone/in combination with NSC 613327. Invest New Drugs. 2014 Oct;32(5):825-37.
[4]. Wu T, et al. Effect of abemaciclib (LY2835219) on enhancement of chemotherapeutic agents in ABCB1 and ABCG2 overexpressing cells in vitro and in vivo. Biochem Pharmacol. 2017 Jan 15;124:29-42.
Cell Assay [1]
Cells are seeded in a 96-well plate, allowed to adhere overnight, and treated with DMSO control (0.1% v/v) or the indicated compounds for 72 h. Cell viability and proliferation are determined using a Cell Counting Kit according to the manufacturer’s instructions. The interaction between Abemaciclib (LY2835219) and mTOR inhibitor is determined using CompuSyn. Combination index (CI) values of 1 indicates and additive drug interaction, whereas a CI of < 1 is synergistic and a CI of > 1 is antagonistic.
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]
Six-week-old BALB/c female nude mice are injected subcutaneously with OSC-19 (1×106) cells. When tumor sizes reach approximately 100 mm3, mice are randomized by tumor size and subjected to each treatment. At least 5 mice per treatment group are included. Each group of mice is dosed via daily oral gavage with vehicle, Abemaciclib (LY2835219) (45 mg/kg/d or 90 mg/kg/d), RAD001 (5 mg/kg/d), or a combination of both. The Abemaciclib (LY2835219) is dissolved in 1% HEC in 20 mM phosphate buffer (pH2.0). Tumor size and body weight are measured twice weekly. Tumor volumes are calculated using the following formula: V=(L × W2)/2 (L, Length; W, width). Mice are gavaged a final time on day 14 and sacrificed the following day. The tumors are removed for Western blot and immunohistochemistry.
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]. Ku BM, et al. The CDK4/6 inhibitor LY2835219 has potent activity in combination with mTOR inhibitor in head and neck squamous cell carcinoma. Oncotarget. 2016 Mar 22;7(12):14803-13.
[2]. Yadav V, et al. The CDK4/6 inhibitor LY2835219 overcomes PLX4032 resistance resulting from MAPK reactivation and cyclin D1 upregulation. Mol Cancer Ther. 2014 Oct;13(10):2253-63.
[3]. Gelbert LM, et al. Preclinical characterization of the CDK4/6 inhibitor LY2835219: in-vivo cell cycle-dependent/independent anti-tumor activities alone/in combination with NSC 613327. Invest New Drugs. 2014 Oct;32(5):825-37.
[4]. Wu T, et al. Effect of abemaciclib (LY2835219) on enhancement of chemotherapeutic agents in ABCB1 and ABCG2 overexpressing cells in vitro and in vivo. Biochem Pharmacol. 2017 Jan 15;124:29-42.
Silydianin is an active constituent of Silybium marianum, with exhibit anti-collagenase, antitumor and anti-elastase activities. Silydianin is a natural protein tyrosine phosphatase 1B (PTP1B) with an IC50 of 17.38 μM. Silydianin has inhibitory effect on the in vitro production and release of oxidative products[1][2][3].
IC50 & Target
Human Endogenous Metabolite
分子量
482.44
Formula
C25H22O10
CAS 号
29782-68-1
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Vostálová J, et al. Skin Protective Activity of Silymarin and its Flavonolignans. Molecules. 2019 Mar 14;24(6).
[2]. Qin N, et al. Identification of flavonolignans from Silybum marianum seeds as allosteric protein tyrosine phosphatase 1B inhibitors. J Enzyme Inhib Med Chem. 2018 Dec;33(1):1283-1291.
[3]. Zielińska-Przyjemska M, et al. An in vitro study of the protective effect of the flavonoid silydianin against reactive oxygen species. Phytother Res. 2006 Feb;20(2):115-9.
PluriSIn 1 (NSC 14613) is an inhibitor of stearoyl-coA desaturase (SCD), and is a pluripotent cell-specific inhibitor.
IC50 & Target
SCD[1]
体外研究 (In Vitro)
PluriSIn 1, a small-molecule inhibitor of stearoyl-coA desaturase (SCD), on induced pluripotent stem cells (iPS)-derived cardiomyocytes (CM). PluriSIn 1 treatment significantly decreases the mRNA and protein level of Nanog, a marker for both cell pluripotency and tumor progression; importantly, we provide evidence that PluriSIn 1 treatment at 20 µM for 1 day significantly induces the apoptosis of Nanog-positive iPS derivates (iPSD). In addition, PluriSIn 1 treatment at 20 µM for 4 days diminished Nanog-positive stem cells in cultured iPSD while not increasing apoptosis of iPS-derived CM. To investigate whether PluriSIn 1 treatment prevents tumorigenicity of iPSD after cell transplantation, we intramyocardially injected PluriSIn 1- or DMSO-treated iPSD in a mouse model of myocardial infarction (MI). DMSO-treated iPSD readily formed Nanog-expressing tumors 2 weeks after injection, which is prevented by treatment with PluriSIn 1. Moreover, treatment with PluriSIn 1 does not change the expression of cTnI, α-MHC, or MLC-2v, markers of cardiac differentiation (P>0.05, n=4). Importantly, PluriSIn 1-treated iPS-derived CM exhibits the ability to engraft and survive in the infarcted myocardium[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
213.24
Formula
C12H11N3O
CAS 号
91396-88-2
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]. Zhang L, et al. Inhibition of stearoyl-coA desaturase selectively eliminates tumorigenic Nanog-positive cells: improving the safety of iPS cell transplantation to myocardium. Cell Cycle. 2014;13(5):762-71.
Cell Assay [1]
The differentiation of iPS cells to cardiomyocytes (CM) is induced by embryoid body (EB) formation. When iPS cells reached 70% confluency in 10-cm dishes, cells are digested using 0.25% trypsin/EDTA. Cell pellets are re-suspended in differentiation medium (DMEM with 20% FBS and 10 ng/mL BMP4) to a final concentration of 200,000 cells/mL. Cell suspensions are added to 6-well plates with Ulta-Low Attachment surfaces for 4 d to initiate EB formation. On day 5, EBs are cultured on 0.1% gelatin-coated dishes for 14 d using CF culture medium for the outgrowth of cardiac structures. At this stage, iPS cells undergoing EB formation are termed iPS derivates (iPSD)[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]. Zhang L, et al. Inhibition of stearoyl-coA desaturase selectively eliminates tumorigenic Nanog-positive cells: improving the safety of iPS cell transplantation to myocardium. Cell Cycle. 2014;13(5):762-71.