THZ2 - CDK 抑制剂 - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemETHZ2Cat. No.: HY-12280CAS No.: 1604810-84-5分式: CHClNO分量: 566.05作靶点: CDK作通路: Cell Cycle/DNA Damage储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 39 mg/mL (68.90 mM)* means soluble, but satu

2、ration unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 1.7666 mL 8.8331 mL 17.6663 mL5 mM 0.3533 mL 1.7666 mL 3.5333 mL10 mM 0.1767 mL 0.8833 mL 1.7666 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。BIOLOGICAL ACTIVITY物活性 THZ2是有效，选择性的 CDK7 抑制剂，IC50 值为 13.9 nM。IC50 & Target CDK7 CDK1 CDK2 C

3、DK513.9 nM (IC50) 96.9 nM (IC50) 222 nM (IC50) 134 nM (IC50)CDK9 CDK81/2 Master of Small Molecules 您边的抑制剂师www.MedChemE194 nM (IC50) 6830 nM (IC50)体外研究 THZ2 selectively targets CDK7 and potently inhibits the growth of triple-negative but not ER/PR+ breastcancer cells. THZ2 at low nanomolar doses also

4、 efficiently suppresses the clonogenic growth of TNBC cellswith IC50 of appr 10 nM. THZ2 induces apoptotic cell death in triple-negative but not ER/PR+ breast cancercells or normal human cells 1.体内研究 THZ2 (10 mg/Kg) markedly reduces the growth rate of tumors in mice and demonstrates an anti-tumoract

5、ivity. Compared to vehicle-treated tumors, tumor tissues isolated from mice treated with THZ2 hasreduced proliferation and increased apoptosis, as indicated by immunostaining against Ki67 and cleavedCaspase 3 respectively. THZ2 in NOD-SCID mice leads to reduced body weight, suggesting that THZ2 mayt

6、be less well-tolerated in this particular mouse strain 1.PROTOCOLCell Assay 1 For 96-well plate assay, cells are plated at the density of 2000 cells per well, and on the next day treated withTHZ1 or THZ2 of various concentrations. After 48-hour incubation, cells are fixed and stained with crystalvio

7、let. The staining is then extracted by adding each well with 10% acetic acid, with absorbance measured at590 nm with 750 nm as a reference.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice: Nude mice (CrTac:NCr-Foxn1nu) are -irradiated with a

8、single dose of 400 rads six hours beforeAdministration 1 transplantation of cells. Breast cancer cells are harvested and resupended in 40% Matrigel-BasementMembrane Matrix, LDEV-free, and then injected (100 L per site) into the fourth pair of mammary fat pads ofmice. Tumors are measured in two dimen

9、sions by using manual calipers. Tumor volume is calculated usingthe formula: V=0.5 length width width. Animal with tumor established (mean tumor volume of appr 200mm3) are randomLy divided into two groups, which are then treated with vehicle (10% DMSO in D5W, 5%dextrose in water) or THZ2 (3 mg/mL, p

10、repared in vehicle solutions) at the dose of 10 mg/kg intraperitoneallytwice daily. Tumor volume is measure every 2-3 days. Upon harvesting tumors, tumors are cut into half, withone half fixed in formalin overnight and then in 70% ethanol for histopathology analysis, and the other halfsnap frozen in

11、 liquid nitrogen for immunoblotting.MCE has not independently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 bioRxiv. 2019 Aug.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Wang Y, et al. CDK7-Dependent Transcriptional Addiction in Triple-Negative Breast Cancer. Cell. 2015 Sep 24;163(1):174-186.McePdfHeight2/2 Master of Small Molecules 您边的抑制剂师www.MedChemECaution: Product has