NCT02 是一种细胞周期蛋白 K 降解剂。NCT02 诱导细胞周期蛋白 K (CCNK) 的泛素化和 CCNK 及其复合物 CDK12 的蛋白酶体降解。NCT02具有研究转移性结直肠癌 (CRC) 的潜力。
NCT02 Chemical Structure
CAS No. : 790245-61-3
规格
是否有货
100 mg
询价
250 mg
询价
500 mg
询价
* Please select Quantity before adding items.
生物活性
NCT02 is a cyclin K degrader. NCT02 induces ubiquitination of cyclin K (CCNK) and proteasomal degradation of CCNK and its complex partner CDK12. NCT02 has the potential for the research of metastatic colorectal cancer (CRC)[1].
分子量
312.39
Formula
C17H16N2O2S
CAS 号
790245-61-3
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]. Dieter SM, et al. Degradation of CCNK/CDK12 is a druggable vulnerability of colorectal cancer. Cell Rep. 2021;36(3):109394.
NCT02 是一种细胞周期蛋白 K 降解剂。NCT02 诱导细胞周期蛋白 K (CCNK) 的泛素化和 CCNK 及其复合物 CDK12 的蛋白酶体降解。NCT02具有研究转移性结直肠癌 (CRC) 的潜力。
NCT02 Chemical Structure
CAS No. : 790245-61-3
规格
是否有货
100 mg
询价
250 mg
询价
500 mg
询价
* Please select Quantity before adding items.
生物活性
NCT02 is a cyclin K degrader. NCT02 induces ubiquitination of cyclin K (CCNK) and proteasomal degradation of CCNK and its complex partner CDK12. NCT02 has the potential for the research of metastatic colorectal cancer (CRC)[1].
分子量
312.39
Formula
C17H16N2O2S
CAS 号
790245-61-3
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]. Dieter SM, et al. Degradation of CCNK/CDK12 is a druggable vulnerability of colorectal cancer. Cell Rep. 2021;36(3):109394.
NCT02 是一种细胞周期蛋白 K 降解剂。NCT02 诱导细胞周期蛋白 K (CCNK) 的泛素化和 CCNK 及其复合物 CDK12 的蛋白酶体降解。NCT02具有研究转移性结直肠癌 (CRC) 的潜力。
NCT02 Chemical Structure
CAS No. : 790245-61-3
规格
是否有货
100 mg
询价
250 mg
询价
500 mg
询价
* Please select Quantity before adding items.
生物活性
NCT02 is a cyclin K degrader. NCT02 induces ubiquitination of cyclin K (CCNK) and proteasomal degradation of CCNK and its complex partner CDK12. NCT02 has the potential for the research of metastatic colorectal cancer (CRC)[1].
分子量
312.39
Formula
C17H16N2O2S
CAS 号
790245-61-3
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]. Dieter SM, et al. Degradation of CCNK/CDK12 is a druggable vulnerability of colorectal cancer. Cell Rep. 2021;36(3):109394.
KIF18A-IN-4 is a moderately potent ATP and microtubule (MT) noncompetitive KIF18A inhibitor (IC50=6.16 μM). KIF18A-IN-4 has selectivity against a large panel of mitotic kinesins and kinases, and does not show any direct effects on tubulin assembly. KIF18A-IN-4 exhibits anti-tumor activity[1].
IC50 & Target
IC50: 6.16 μM (KIF18A)[1]
体外研究 (In Vitro)
KIF18A-IN-4 (15 μM; 24 hours) induces a phenotype characterized by multipolar spindle arrays emanating from multiple pericentriolar material (PCM) centers in mitotic MDA-MB-157 cells (pH3+)[1]. KIF18A-IN-4 (0-10 μM; overnight) has an EC50 of 6.35 μM in OVCAR-3 cells by the mitotic index assay[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
413.53
Formula
C22H27N3O3S
CAS 号
1197522-21-6
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]. Tamayo NA, et al. Targeting the Mitotic Kinesin KIF18A in Chromosomally Unstable Cancers: Hit Optimization Toward an In Vivo Chemical Probe. J Med Chem. 2022;65(6):4972-4990.
KIF18A-IN-4 is a moderately potent ATP and microtubule (MT) noncompetitive KIF18A inhibitor (IC50=6.16 μM). KIF18A-IN-4 has selectivity against a large panel of mitotic kinesins and kinases, and does not show any direct effects on tubulin assembly. KIF18A-IN-4 exhibits anti-tumor activity[1].
IC50 & Target
IC50: 6.16 μM (KIF18A)[1]
体外研究 (In Vitro)
KIF18A-IN-4 (15 μM; 24 hours) induces a phenotype characterized by multipolar spindle arrays emanating from multiple pericentriolar material (PCM) centers in mitotic MDA-MB-157 cells (pH3+)[1]. KIF18A-IN-4 (0-10 μM; overnight) has an EC50 of 6.35 μM in OVCAR-3 cells by the mitotic index assay[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
413.53
Formula
C22H27N3O3S
CAS 号
1197522-21-6
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]. Tamayo NA, et al. Targeting the Mitotic Kinesin KIF18A in Chromosomally Unstable Cancers: Hit Optimization Toward an In Vivo Chemical Probe. J Med Chem. 2022;65(6):4972-4990.
KIF18A-IN-4 is a moderately potent ATP and microtubule (MT) noncompetitive KIF18A inhibitor (IC50=6.16 μM). KIF18A-IN-4 has selectivity against a large panel of mitotic kinesins and kinases, and does not show any direct effects on tubulin assembly. KIF18A-IN-4 exhibits anti-tumor activity[1].
IC50 & Target
IC50: 6.16 μM (KIF18A)[1]
体外研究 (In Vitro)
KIF18A-IN-4 (15 μM; 24 hours) induces a phenotype characterized by multipolar spindle arrays emanating from multiple pericentriolar material (PCM) centers in mitotic MDA-MB-157 cells (pH3+)[1]. KIF18A-IN-4 (0-10 μM; overnight) has an EC50 of 6.35 μM in OVCAR-3 cells by the mitotic index 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.
分子量
413.53
Formula
C22H27N3O3S
CAS 号
1197522-21-6
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]. Tamayo NA, et al. Targeting the Mitotic Kinesin KIF18A in Chromosomally Unstable Cancers: Hit Optimization Toward an In Vivo Chemical Probe. J Med Chem. 2022;65(6):4972-4990.
CRM1 degrader 1 (1l) is a low toxic chromosome region maintenance 1 (CRM1) degrader. CRM1 is the sole nuclear exporter of several tumor suppressor, a growth regulatory protein as an attractive cancer drug target. CRM1 degrader 1 induces the apoptosis in gastric carcinoma and selectively inhibits proliferation of gastric cancer[1].
分子量
260.33
Formula
C16H20O3
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]. Xu HW, et al. A low toxic CRM1 degrader: Synthesis and anti-proliferation on MGC803 and HGC27. Eur J Med Chem. 2020;206:112708.
USP7-IN-9 is a highly potent ubiquitin-specific protease 7 (USP7) inhibitor with an IC50 value of 40.8 nM. USP7-IN-9 can induce apoptosis and arrest cell progression at G0/G1 and S phases in RS4; 11 cells. USP7-IN-9 reduces the protein levels of oncoproteins MDM2 and DNMT1 and increases the protein levels of tumor suppressors p53 and p21[1].
IC50 & Target
IC50: 40.8 nM (USP7)[1]
体外研究 (In Vitro)
USP7-IN-9 (compound L55) (0-50 μM; 3 or 6 days) exhibits inhibitory activity against cancer cells[1]. USP7-IN-9 (1 μM; 0-72 hours) reduces the proportions of G2/M cells, and does not change the proportions of G0/G1 and S cells[1]. USP7-IN-9 (0.1-1 μM; 24 hours) reduces the protein levels of MDM2 and DNMT1 in a dose-dependent manner, and increases the protein levels of p53 and p21[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Proliferation Assay
Cell Line:
LNCaP, RS4; 11, HCT 116, NB4, K562 and HuH-7 cells[1]
Concentration:
0-50 μM
Incubation Time:
LNCaP, 6 days; RS4; 11, HCT 116, HuH-7, K562 and NB4, 3 days
Result:
Exhibited high inhibitory activity against LNCaP and RS4; 11 cells, with IC50s of 29.6 nM and 41.6 nM, respectively, and weak inhibitory activity on HCT 116, NB4, K562 and HuH-7 cells.
Cell Cycle Analysis
Cell Line:
RS4; 11 cells[1]
Concentration:
1 μM
Incubation Time:
0, 24, 48 and 72 hours
Result:
Reduced the proportions of G2/M cells, while the proportions of G0/G1 and S cells were not apparently altered.
Western Blot Analysis
Cell Line:
RS4; 11 cells[1]
Concentration:
0.1, 0.3 and 1 μM
Incubation Time:
24 hours
Result:
Reduced the protein levels of MDM2 and DNMT1 in a dose-dependent manner, and increased the protein levels of p53 and p21.
分子量
779.08
Formula
C32H33ClF6N6O8
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]. Li M, Liu S, Chen H, et al. N-benzylpiperidinol derivatives as novel USP7 inhibitors: Structure-activity relationships and X-ray crystallographic studies. Eur J Med Chem. 2020;199:112279.
Amphethinile is an anti-tubulin agent. The affinity constant for the association (Ka) of Amphethinile with tubulin is 1.3 μM.
IC50 & Target
Ka: 1.3 μM (Tubulin)[1]
体外研究 (In Vitro)
Amphethinile shows a remarkable similarity to colchicine in terms of its binding to tubulin and inhibition of microtubular assembly. Amphethinile binds strongly to microtubule protein (Ka=1.3 μM). This interaction has been shown to be capable of inhibiting tubulin assembly, but shows no rapid stimulation of disassembly when added to assembled tubulin. The concentration of amphethinile required to inhibit assembly by 50% (12 μM) is very similar to that for colchicine (11 μM). Amphethinile has been shown to be capable of competing for colchicine binding sites but not for those of the vinca alkaloids. Amphethinile can also be shown to stimulate the GTPase activity of tubulin in a manner similar to that observed for combretastatin A4 and 2-methoxy-5-(2′,3′,4′-trimethoxyphenyl) tropolone (MTPT)[1]. Amphethinile has been shown to cause a G2/M phase block in the cell cycle. In addition, this agent has been shown to be equally toxic toward parental and daunorubicin-resistant P388 cells. Whereas resistance in this cell line is associated with decreased drug accumulation in the case of daunorubicin, vincristine and vinblastine, this effect is much less pronounced for amphethinile[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)
Pharmacokinetic studies in male mice are undertaken. Area under the curve values (AUC), show that levels of 313 μg/L per hour are attained at doses equivalent to the LD10. The alpha half life is 8 min after a bolus intravenous injection. The beta half life is 100 min and relatively independent of dose level[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
265.33
Formula
C15H11N3S
CAS 号
91531-98-5
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]. McGown AT, et al. Interaction of the novel agent amphethinile with tubulin. Br J Cancer. 1989 Jun;59(6):865-8.
[2]. McGown AT, et al. Pre-clinical studies of a novel anti-mitotic agent, amphethinile. Br J Cancer. 1988 Feb;57(2):157-9.
Cell Assay
The volume of methanol in the final incubation mixture is <1%, which does not modify the uptake of any of the drugs used in either drug sensitive or resistant lines. In addition, the same level of methanol is used in the control cultures. Drug incubations (1O μM, 2h, 37°C) are performed in RPMI medium in the presence or absence of horse serum (10%). Cell suspensions (100 mL) are centrifuged (800 g, 10 min, 4°C), washed in PBS, lysed in distilled water by sonication, and the drug extracted into CHC13. The amphethinile concentration is determined spectrophotometrically (λ=304 nm) relative to a standard curve[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
Mouse: Initial toxicity studies on this agent are performed under contract in MFI-strain male mice following an acute i.v. and i.p. administration as well as a 4-weekly 5 day sub acute study. Preclinical toxicology is undertaken using the clinically formulated drug. The formulation consisted of 10 g amphethinile and 100 g Solutol HS15 diluted to 200 mL with 70% ethanolic citrate buffer at pH 6.0. The resulting drug concentration is 50mg mL[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]. McGown AT, et al. Interaction of the novel agent amphethinile with tubulin. Br J Cancer. 1989 Jun;59(6):865-8.
[2]. McGown AT, et al. Pre-clinical studies of a novel anti-mitotic agent, amphethinile. Br J Cancer. 1988 Feb;57(2):157-9.
MS67 is a potent and selective WD40 repeat domain protein 5 (WDR5) degrader with a Kd of 63 nM. MS67 is inactive against other protein methyltransferases, kinases, GPCRs, ion channels, and transporters. MS67 shows potent acticancer effects[1].
IC50 & Target[1]
VHL
WDR5
63 nM (Kd)
体外研究 (In Vitro)
MS67 (0.001-1 μM) induces WDR5 degradation at a concentration as low as 1 nM. MS67 induces WDR5 depletion much more effectively in all six mixed lineage leukemia (MLL)-r acute myeloid leukemia (AML) and four pancreatic ductal adenocarcinoma (PDAC) cell lines without a hook effect and in a concentration-dependent manner in PDAC cells[1]. MS67 decreases H3K4me2/3 in both MV4;11 and MIA PaCa-2 cells, whereas other examined histone methylation marks such as H3K9me3, H3K27me3, and H3K36me3 are not affected . MS67 is effective in suppressing both WDR5-related gene expression programs and WDR5/MLL-induced H3K4 methylations on chromatin[1]. The GI50 values of MS67 in the two most sensitive AML lines, MV4;11 and EOL-1, are 15 nM and 38 nM, respectively. MLL-r acute leukemia cell lines including MV4;11, EOL-1, MOLM13, KOPN8, RS4;11, and THP-1 are sensitive to MS67, whereas leukemia cell lines that did not harbor MLL-r (including K562, HL60, and a murine AML line transformed by Hoxa9 plus Meis1) are insensitive to MS67[1]. . MS67 binds to VCB (VHL-Elongin C-Elongin B ternary complex), with a Kd of 140 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.
Induced WDR5 degradation at a concentration as low as 1 nM with DC50 of 3.7 nM.
体内研究 (In Vivo)
MS67 (75 mg/kg; i.p.; twice daily; 5 days a week; for 20 days) significantly inhibits tumor growth in vivo and prolongs survival of the treated mice[1]. After a single intraperitoneal (i.p.) injection of MS67 at a dose of 75 mg/kg, the Cmax reached at about 4.2 μM, and the concentration of MS67 retained above 0.5 μM over 12 hours[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:
MV4;11 MLL-r AML xenograft mouse[1]
Dosage:
75 mg/kg
Administration:
i.p.; twice daily; 5 days a week; for 20 days
Result:
Inhibited tumor growth in vivo.
分子量
1030.14
Formula
C52H59F4N9O7S
CAS 号
2407452-77-9
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]. Xufen Yu, et al. A selective WDR5 degrader inhibits acute myeloid leukemia in patient-derived mouse models. Sci Transl Med. 2021 Sep 29;13(613):eabj1578.
W-7 hydrochloride is a selective calmodulin antagonist. W-7 hydrochloride inhibits the Ca2+-calmodulin-dependent phosphodiesterase and myosin light chain kinase with IC50 values of 28 μM and 51 µM, respectively[1][2]. W-7 hydrochloride induces apoptosis and has antitumor activity[3].
W-7 is distributed mainly in the cytoplasm, and inhibits proliferation of Chinese hamster ovary K1 (CHO-K1) cells. W-7 selectively blocks the phase of the cell cycle (G1/S boundary phase) in a manner. 25 μM W-7 arrests the growth of the cells at the G1/S boundary phase of the cell cycle[1]. W-7 (100 μM) exhibits a similar extent of antagonism between the contractile responses to carbachol and KCl. The increase in myosin light chain (P-LC) phosphate content in response to 1-min stimulation with 10 μM carbachol is inhibited by W-7. W-7 antagonizes the smooth muscle contraction through the inhibition of the initial increase in the P-LC phosphorylation[2]. Treatment with W-7 results in the dose-dependent inhibition of cell proliferation in various human multiple myeloma cell lines. W-7 induces G1 phase cell cycle arrest by downregulating cyclins and upregulating p21cip1. W-7 induces apoptosis via caspase activation; this occurred partly through the elevation of intracellular calcium levels and mitochondrial membrane potential depolarization and through inhibition of the STAT3 phosphorylation and subsequent downregulation of Mcl-1 protein[3]. W-7 competitively inhibits Ca2+/calmodulin-dependent phosphodiesterase with a Ki value of 300 μM[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.
体内研究 (In Vivo)
W-7 (3 mg/kg; intraperitoneal injection; on 5 consecutive days per week; female BALB/c nu mice) treatment significantly reduces tumor growth in a murine MM model[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.
Animal Model:
Female BALB/c nu mice (6-week-old) injected with RPMI 8226 cells[3]
Dosage:
3 mg/kg
Administration:
Intraperitoneal injection; on 5 consecutive days per week
Result:
Significantly reduced tumor growth in a murine MM model.
分子量
377.33
Formula
C16H22Cl2N2O2S
CAS 号
61714-27-0
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. H Hidaka, et al. N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide, a Calmodulin Antagonist, Inhibits Cell Proliferation. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4354-7.
[2]. M Asano. Divergent Pharmacological Effects of Three Calmodulin Antagonists, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), Chlorpromazine and Calmidazolium, on Isometric Tension Development and Myosin Light Chain Phosphorylation in Intact Bovine Tracheal Smooth Muscle. J Pharmacol Exp Ther. 1989 Nov;251(2):764-73.
[3]. H Itoh, et al. Direct Interaction of Calmodulin Antagonists With Ca2+/calmodulin-dependent Cyclic Nucleotide Phosphodiesterase. J Biochem. 1984 Dec;96(6):1721-6.
[4]. Shigeyuki Yokokura, et al. Calmodulin Antagonists Induce Cell Cycle Arrest and Apoptosis in Vitro and Inhibit Tumor Growth in Vivo in Human Multiple Myeloma. BMC Cancer. 2014 Nov 26;14:882.
Epothilone B is a microtubule stabilizer with a Ki of 0.71μM. It acts by binding to the αβ-tubulin heterodimer subunit which causes decreasing of αβ-tubulin dissociation.
IC50 & Target
EC0.01: 1.8 μM (Microtubule/Tubulin)[1]
体外研究 (In Vitro)
Epothilone B inhibits HCT116 cells with IC50 of 0.8 nM in HCT-116 cell line cytotoxicity assay[1]. Epothilone B (Patupilone) is a microtubule (MT) targeting agent. As shown by MTT cell proliferation assay, after 72 h of treatment Epothilone B efficiently inhibits cell growth with an IC50 of 6 nM, while concentrations ≤1 nM are not cytotoxic. Epothilone B significantly inhibits transwell cell migration at the non-cytotoxic concentration of 1 nM, and the effect is more evident at 10 nM[2]. Epothilone B (Patupilone) is a novel, non-taxane-related and nonneurotoxic microtubule-stabilizing agent in human medulloblastoma cell lines. Epothilone B reduces the proliferative activity in the D341 cell line, with an IC50 of 0.53 nM; in the D425Med cell line, with an IC50 of 0.37 nM; and in the DAOY cell line, with an IC50 of 0.19 nM. In the D341Med cell line, the effect of Epothilone B on clonogenic survival is at dose range of Epothilone B similar to the level of proliferative activity and viability (IC50, 0.50-0.75 nM). However, the clonogenicity of D425Med and DAOY cells is already strongly reduced at a 10-fold lower concentration of Epothilone B (IC50, 30 pM). These results overall demonstrate that Epothilone B is highly potent against different medulloblastoma cell lines[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)
Treatment with Epothilone B (Patupilone) or ionizing radiation alone results in a partial tumor growth suppression over 10 days, whereas combined treatment exerts a strong supra-additive tumor growth control, with complete tumor regression in the follow-up period (P<0.005, for ionizing radiation or Epothilone B alone vs combined treatment)[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
507.68
Formula
C27H41NO6S
CAS 号
152044-54-7
中文名称
埃博霉素 B
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Regueiro-Ren A, et al. Synthesis and biological activity of novel epothilone aziridines. Org Lett. 2001 Aug 23;3(17):2693-6.
[2]. Pagano A, et al. Epothilone B inhibits migration of glioblastoma cells by inducing microtubule catastrophes and affecting EB1 accumulation at microtubule plus ends. Biochem Pharmacol. 2012 Aug 15;84(4):432-43.
[3]. Oehler C, et al. The microtubule stabilizer patupilone (epothilone B) is a potent radiosensitizer in medulloblastoma cells. Neuro Oncol. 2011 Sep;13(9):1000-10.
Kinase Assay [3]
Asp-Glu-Val-Asp (DEVD)ase activity is determined in cytosolic cell extracts. Cells are treated with increasing concentrations of Epothilone B (Patupilone) for 6, 12, 24, and 48 h. Cells are harvested thereafter by trypsin/EDTA, centrifuged, and washed with precooled PBS. The cell pellet is suspended in 5 volumes of precooled buffer A (20 mM HEPES-KOH [pH 7.5], 10 mM KCl, 1.5 mM MgCl2, 1 mM sodium EDTA, 1 mM sodium EGTA, 1 mM dithiothreitol [DDT], 250 mM sucrose, and 0.1 mM phenylmethylsulfonyl fluoride [PMSF] supplemented with protease inhibitors [5 mg/mL pepstatin A, 10 mg/mL leupeptin, 2 mg/mL aprotinin, 2 mg/mL DTT, and 1 mM of PMSF]). After incubation on ice for 15 min, the cells are disrupted by freezing and thawing. Cell lysates are centrifuged at 1000g for 10 min at 4°C, and the supernatant is further centrifuged at 100 000g for 30 min. The resulting supernatant (S-100 fraction) is stored at −80°C. To determine caspase 3-like activity, 75 μg of protein from the S-100 fraction is incubated at 37°C with the colorimetric caspase 3 substrate N-acetyl-Asp-Glu-Val-Asp p-nitroanilide (100 mM; Ac-DEVD-pNA) and 1 mM dATP in a final volume of 120 μL. Cleavage of the caspase substrate is monitored at 405 nm using a GenTec spectrophotometer[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.
Cell Assay [2]
Human glioblastoma cells (U87MG, ATCC) are routinely maintained at 37°C and 5% CO2 in EMEM medium, with NEAA, containing 10% fetal bovine serum, 2 mM of glutamine, 1% penicillin and streptomycin. U87MG cells are used for no more than 15 passages. Cells are seeded in 96-well plates (5000 cells/well). After 24 h cells are treated with Epothilone B. Growth inhibition of U87MG cells is measured after 72 h of drug treatment by using the MTT cell proliferation assay[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 [3]
Mice[3] D425Med cells (6×106) are injected subcutaneously on the backs of 4-6-week-old athymic nude mice. Tumor volumes are determined from caliper measurements of tumor length (L) and width (l) according to the formula (L×l2)/2. Tumors are allowed to expand to a volume of 200 mm3 (±10%) before treatment start. With the use of a customized shielding device, mice are given strictly loco regional radiotherapy of 3×3 Gy on 3 consecutive days using a Gulmay 200 kV X-ray unit at 100 cGy/min at room temperature. Epothilone B (2 mg/kg; dissolved in 30% PEG-300/70% saline) is applied intravenously 24 h before the first treatment with ionizing radiation (at day 0 of the treatment; n=5 per group). Tumor growth is monitored daily.
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]. Regueiro-Ren A, et al. Synthesis and biological activity of novel epothilone aziridines. Org Lett. 2001 Aug 23;3(17):2693-6.
[2]. Pagano A, et al. Epothilone B inhibits migration of glioblastoma cells by inducing microtubule catastrophes and affecting EB1 accumulation at microtubule plus ends. Biochem Pharmacol. 2012 Aug 15;84(4):432-43.
[3]. Oehler C, et al. The microtubule stabilizer patupilone (epothilone B) is a potent radiosensitizer in medulloblastoma cells. Neuro Oncol. 2011 Sep;13(9):1000-10.
Palmitic acid is a long-chain saturated fatty acid commonly found in both animals and plants. PA can induce the expression of glucose-regulated protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP) in in mouse granulosa cells[1][2].
IC50 & Target
Human Endogenous Metabolite
Clinical Trial
分子量
256.42
Formula
C16H32O2
CAS 号
57-10-3
中文名称
棕榈酸
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Harada H, et al. Antitumor activity of palmitic acid found as a selective cytotoxic substance in a marine red alga. Anticancer Res. 2002 Sep-Oct;22(5):2587-90.
Gossypol binds to Bcl-xL protein and Bcl-2 protein with Kis of 0.5-0.6 μM and 0.2-0.3 mM, respectively.
IC50 & Target[1]
Bcl-xL
0.5-0.6 μM (Ki)
Bcl-2
0.2-0.3 mM (Ki)
体外研究 (In Vitro)
Gossypol, a natural product isolated from cottonseeds and roots that has been studied as an anticancer agent. The racemic form of Gossypol [(±)-Gossypol] is tested in several clinical trials and is well tolerated. The racemic form Gossypol ((±)-Gossypol) binds to Bcl-xL protein with a Ki of 0.5 to 0.6 μM. (±)-Gossypol also potently binds to Bcl-2 protein with a Ki value of 0.2-0.3 mM. The natural racemic Gossypol has two enantiomers, namely the (-)-Gossypol and (+)-Gossypol enantiomers. The racemic form and each of the enantiomers of Gossypol are tested against UM-SCC-6 and UM-SCC-14A in 6-day MTT assays. (-)-Gossypol exhibits greater growth inhibition relative to (±)-Gossypol than (+)-Gossypol in both cell lines tested (P<0.001). An intermediate growth inhibitory effect is observed with (±)-Gossypol but this effect is only observed at the higher dose of Gossypol (10 μM, P<0.0001)[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.
Clinical Trial
分子量
518.55
Formula
C30H30O8
CAS 号
303-45-7
中文名称
棉酚；棉籽酚；棉子酚；棉子醇
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Oliver CL, et al. In vitro effects of the BH3 mimetic, (-)-Gossypol, on head and neck squamous cell carcinoma cells. Clin Cancer Res. 2004 Nov 15;10(22):7757-63.
Cell Assay [1]
Two representative UM-SCC cell lines, UM-SCC-6 and UM-SCC-14A, are continuously exposed to 0 (vehicle control), 5 or 10 μM (±)-Gossypol, (-)-Gossypol or (+)-Gossypol in a 6-day MTT cell survival 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.
参考文献
[1]. Oliver CL, et al. In vitro effects of the BH3 mimetic, (-)-Gossypol, on head and neck squamous cell carcinoma cells. Clin Cancer Res. 2004 Nov 15;10(22):7757-63.
AZ82 is a selective kinesin-like protein KIFC1 (HSET/KIFC1) inhibitor, with a Ki of 43 nM and an IC50 of 300 nM for KIFC1.
IC50 & Target[1][2]
HSET/KIFC1
300 nM (IC50)
HSET/KIFC1
43 nM (Ki)
体外研究 (In Vitro)
AZ82 is shown to specifically induce multipolar spindles in BT-549 cells, but not in cancer cells with normal centrosome number, such as HeLa[1]. AZ82 binds specifically to KIFC1/MT complex but not to KIFC1 or MT alone. Treatment with AZ82 caused centrosome declustering in BT-549 breast cancer cells with amplified centrosomes. AZ82 inhibits both processes with an IC50 of 0.90 ± 0.09 μM for mant-ATP binding and 1.26 ± 0.51 μM for mant-ADP releasing[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
560.63
Formula
C28H31F3N4O3S
CAS 号
1449578-65-7
运输条件
Room temperature in continental US; may vary elsewhere.
G15 是一种高亲和力和选择性 G 蛋白偶联雌激素受体 (GPER/GPR30) 拮抗剂，Ki 值为 20 nM。
G15 Chemical Structure
CAS No. : 1161002-05-6
规格
价格
是否有货
数量
Free Sample (0.1-0.5 mg)
Apply now
10 mM * 1 mL in DMSO
￥935
In-stock
5 mg
￥850
In-stock
10 mg
￥1400
In-stock
50 mg
￥4300
In-stock
100 mg
￥7400
In-stock
200 mg
询价
500 mg
询价
* Please select Quantity before adding items.
G15 相关产品
•相关化合物库:
Bioactive Compound Library Plus
Anti-Cancer Compound Library
Anti-Breast Cancer Compound Library
生物活性
G15 is a high affinity and selective G-protein-coupled estrogen receptor (GPER/GPR30) antagonist with a Ki of 20 nM[1][2].
IC50 & Target
Ki: 20 nM (GPER/GPR30)[2]
体外研究 (In Vitro)
G15 (0.1-10 μM; 2 days) inhibits GPER-mediated proliferation stimulated by 17β-estradiol (E2) in A549 and H1793 cell lines[1]. G15 (1 μM; 48 hours) inhibits the response of GPER stimulated by E2 and G1 in A549 and H1793 cell lines[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 Proliferation Assay[1]
Cell Line:
A549, H1793 cell lines
Concentration:
0.1, 1, 10 μM (combination with 10 nM E2)
Incubation Time:
2 days
Result:
Inhibited GPER-mediated proliferation stimulated by E2.
Western Blot Analysis[1]
Cell Line:
A549, H1793 cell lines
Concentration:
1 μM (combination with 10 nM E2 and 10 nM G1)
Incubation Time:
48 hours
Result:
Inhibited the response of GPER stimulated by E2 and G1.
体内研究 (In Vivo)
G15 (1.46 mg/kg; i.h.; twice a week for 14 weeks) decreases the number of tumor nodules and tumor index increased by the E2 or G1 group in urethane-induced adenocarcinoma 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.
[1]. Liu C, et al. G-Protein-Coupled Estrogen Receptor Antagonist G15 Decreases Estrogen-Induced Development of Non-Small Cell Lung Cancer. Oncol Res. 2019 Feb 21;27(3):283-292
[2]. Girgert R, et al. Estrogen Signaling in ERα-Negative Breast Cancer: ERβ and GPER. Front Endocrinol (Lausanne). 2019 Jan 9;9:781.
I-CBP112 is a specific and potent acetyl-lysine competitive protein-protein interaction inhibitor, that inhibits the CBP/p300 bromodomains, enhances acetylation by p300.
I-CBP112 significantly enhances acetylation by p300 at the histone H3K18 and H3K23 sites. I-CBP112 stimulated H3K18ac by ~3-fold, I-CBP112 induced enhances acetylation of these same sites by CBP as well as at H4K5. The EC50’s of activation of I-CBP112 on p300- and CBP-mediated H3K18 acetylation are ~2 μM[1]. Exposure of human and mouse leukemic cell lines to I-CBP112 results in substantially impaired colony formation and induces cellular differentiation without significant cytotoxicity. Exposure of the BioMAP primary cell panel to I-CBP112 results in a unique response on cytokine and marker protein expression[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)
I-CBP112 significantly reduces the leukemia-initiating potential of mLL-AF9+ AmL cells in a dose-dependent manner in vitro and in vivo. The synergistic effects of I-CBP112 and current standard therapy (doxorubicin) as well as emerging treatment strategies (BET inhibition) provide new opportunities for combinatorial treatment of leukemia and potentially other cancers[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
468.59
Formula
C27H36N2O5
CAS 号
1640282-31-0
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Zucconi BE, et al. Modulation of p300/CBP Acetylation of Nucleosomes by Bromodomain LigandI-CBP112. Biochemistry. 2016 Jul 12;55(27):3727-34.
[2]. Picaud S, et al. Generation of a Selective Small Molecule Inhibitor of the CBP/p300 Bromodomain for Leukemia Therapy. Cancer Res. 2015 Dec 1;75(23):5106-19.
Cell Assay [1]
I-CBP112 is dissolved in DMSO and diluted with appropriate medium before use. Cells (6000 KG1a and 13000 LNCaP cells/well) are plated in 96-well flat-bottom plates approximately 24 h prior to drug treatment. After 24 h, 10–20% fetal bovine serum-containing medium is replaced with 2.5% serum medium, and cells are treated with I-CBP112 in 0.18% DMSO; 0.18% DMSO is shown to have negligible cell growth effects under the conditions used in our experiments. After being exposed to I-CBP112 for 66 h, cells are subjected to a final concentration of 0.476% [3H]thymidine per well and allowed to proliferate for an additional 6 h (exposure to I-CBP112 for a total of 72 h). Cells are harvested, and the counts of 3H in each well are taken relative to those treated with vehicle alone to quantify the effect of the ligand on proliferation[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: Leukemic blasts expressing MLL-AF9 are treated in liquid culture with 5 μM of I-CBP112 for 3 days. Control cells are exposed to the corresponding concentration of the DMSO vehicle. Treated cells are then transplanted into sublethally irradiated syngeneic mice via tail vein injection. Upon the development of signs of disease the mice are sacrificed and analysed[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]. Zucconi BE, et al. Modulation of p300/CBP Acetylation of Nucleosomes by Bromodomain LigandI-CBP112. Biochemistry. 2016 Jul 12;55(27):3727-34.
[2]. Picaud S, et al. Generation of a Selective Small Molecule Inhibitor of the CBP/p300 Bromodomain for Leukemia Therapy. Cancer Res. 2015 Dec 1;75(23):5106-19.
Calyculin A ((-)-Calyculin A) 是有效，可渗透细胞的蛋白磷酸酶 1 (PP1) 和蛋白磷酸酶 2A (PP2A) 抑制剂，其 IC50 值分别为 2 nM 和 0.5-1 nM。
Calyculin A Chemical Structure
CAS No. : 101932-71-2
规格
价格
是否有货
数量
10 μg (0.5 mM * 20 μL in DMSO)
￥1200
In-stock
25 μg (0.5 mM * 50 μL in DMSO)
￥2050
In-stock
50 μg (0.5 mM * 100 μL in DMSO)
￥3680
In-stock
100 μg (0.5 mM * 200 μL in DMSO)
￥5530
In-stock
* Please select Quantity before adding items.
生物活性
Calyculin A ((-)-Calyculin A) is a potent and cell-permeable protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A) inhibitor with IC50s of 2 nM and 0.5-1 nM, respectively[1].
IC50 & Target
IC50: 2 nM (PP1); 0.5-1 nM (PP2A)[1]
体外研究 (In Vitro)
Calyculin A (1-10 nM; 24 hours) induces cytotoxicity in MG63 cells in a dose-dependent manner up to 10 nM in MG63 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 Cytotoxicity Assay[2]
Cell Line:
Human osteosarcoma MG63 cells
Concentration:
0, 1, 2, 5, 10 nM
Incubation Time:
24 hours
Result:
Treatment with 0.1 nM for 24 h had a minimal effect on MG63 cell survival. Cell rounding and shrinking were obvious in the cultures treated for 24 h with 5 nM. The level of the cell viability treated with 10 nM was 27% that of the control cultures.
分子量
1009.17
Formula
C50H81N4O15P
CAS 号
101932-71-2
中文名称
花萼海绵诱癌素；花萼海绵体诱癌素A
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Solution, -20°C, 2 years
参考文献
[1]. Ishihara H, et al. Calyculin A and okadaic acid: inhibitors of protein phosphatase activity. Biochem Biophys Res Commun. 1989 Mar 31;159(3):871-7.
[2]. Hiroaki Tanaka,et al. Calyculin A induces apoptosis and stimulates phosphorylation of p65NF-kappaB in human osteoblastic osteosarcoma MG63 cells. Int J Oncol. 2007 Aug;31(2):389-96.
CCG215022 is a G protein-coupled receptor kinases (GRKs) inhibitor with IC50s of 0.15±0.07 μM, 0.38±0.06 μM and 3.9±1 μM for GRK2, GRK5 and GRK1, respectively.
CCG215022 has nanomolar potency against both GRK2 and GRK5 and is at least 20-fold more potent than Paroxetine. In the course of a GRK2 structure-based drug design campaign, CCG215022 exhibits nanomolar IC50 values against both GRK2 and GRK5 and good selectivity against other closely related kinases such as GRK1 and PKA. Treatment of murine cardiomyocytes with CCG215022 results in significantly increases contractility at 20-fold lower concentrations than Paroxetine, an inhibitor with more modest selectivity for GRK2[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
499.50
Formula
C26H22FN7O3
CAS 号
1813527-81-9
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]. Homan KT, et al. Crystal Structure of G Protein-coupled Receptor Kinase 5 in Complex with a Rationally DesignedInhibitor. J Biol Chem. 2015 Aug 21;290(34):20649-59.
Kinase Assay [1]
GRK5 and urea-washed bovine rod outer segments (ROS) are mixed in the dark in buffer containing 20 mM HEPES, pH 7.5, 4 mM MgCl2, and 2 mM EDTA and incubated for 35 min at room temperature. The reaction mixtures are exposed to ambient fluorescent light for 1 min prior to initiation of the reaction by addition of ATP (with [γ-32P]ATP) to a final concentration of 1 mM. Final concentration of GRK5 is 100 nM and ROS is between 0.75 and 24 μM. Reactions are initiated at room temperature, and samples are taken at 2-5 min and then quenched with SDS-PAGE loading dye. Proteins are separated using SDS-PAGE, gel is dried, and the incorporation of γ-32P is detected using a phosphor storage screen. Rates at 0 min are plotted against the ROS concentration, and Vmax and Kmvalues are determined using the Michaelis-Menten equation. Vmax of each curve is normalized to the Vmax of GRK5561 run in parallel. Melting point determinations in response to 200 μM CCG215022 are performed in 20 mM HEPES, pH 7.0, 5 mM MgCl2, 2 mM DTT, 1 mM CHAPS at a final GRK5 concentration of 0.2 mg/mL and 100 μM anilinonaphthalene-8-sulfonic acid using a Fluor plate reader. Melting points of GRK5 variants are assayed in a buffer containing 20 mM HEPES, pH 8.0, 200 mM NaCl, 2 mM DTT, 2.5 mM MgCl2, and 0.1 mM anilinonaphthalene-8-sulfonic acid with or without 5 mM ATP. Final GRK5 concentration for these assays is 0.1 mg/mL[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]. Homan KT, et al. Crystal Structure of G Protein-coupled Receptor Kinase 5 in Complex with a Rationally DesignedInhibitor. J Biol Chem. 2015 Aug 21;290(34):20649-59.
Thiocolchicine, a derivative modified in the C Ring of Colchicine (HY-16569) with enhanced biological properties. Thiocolchicine is a potent inhibitor of tubulin polymerization (IC50=2.5 µM) and competitively binds to tubulin with a Ki of 0.7 µM. Thiocolchicine induces cell apoptosis[1][2]. Thiocolchicine can be used as an ADC cytotoxin in ADC technology.
体外研究 (In Vitro)
Thiocolchicine is against MCF-7, LoVo, LoVo/DX, A-549 and BALB/3T3 cells with IC50 values of 0.01 μM, 0.021 μM, 0.398 μM, 0.011 μM and 0.114 μM, respectively[3].Thiocolchicine (1 nM-100 μM; 24-72 hours) shows a relationship between cell cycle blocking activity and growth inhibition in breast cancer cells. It inhibits cell proliferation of MDA-MB-231 and multidrug resistant (MDR) MCF-7 ADRr breast cancer cells with IC50s of 0.6 nM and 400 nM, respectively, as well as MDR CEM-VBL leukemia cells (IC50=50 nM)[2].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
415.50
Formula
C22H25NO5S
CAS 号
2730-71-4
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]. Klaus M.Hahn, et al. Structural requirements for the binding of colchicine analogs to tubulin: the role of the C-10 substituent. Bioorganic & Medicinal Chemistry Letters.Volume 1, Issue 9, 1991, Pages 471-476
[2]. R De Vincenzo, et al. Antiproliferative Activity of Colchicine Analogues on MDR-positive and MDR-negative Human Cancer Cell Lines. Anticancer Drug Des. 1998 Jan;13(1):19-33.
