PF-477736-PF-00477736-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEPF 477736Cat. No.: HY-10032CAS No.: 952021-60-2Synonyms: PF 00477736分式: CHNO分量: 419.48作靶点: Checkpoint Kinase (Chk)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 : 1

2、25 mg/mL (297.99 mM; Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.3839 mL 11.9195 mL 23.8390 mL5 mM 0.4768 mL 2.3839 mL 4.7678 mL10 mM 0.2384 mL 1.1920 mL 2.3839 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。体内实验 请根据您的实验动物和给药式选择适当的溶解案，配制前请先配制澄清的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的作

3、液，建议您现现配，当天使；澄清的储备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.08 mg/mL (4.96 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.08 mg/mL (4.96 mM); Clear solution1/3 Master of Small Molecules 您边的抑制剂师ww

4、w.MedChemEBIOLOGICAL ACTIVITY物活性 PF 477736种有效的，ATP 竞争性的 Chk1 抑制剂，Ki 为 0.49 nM，对其选择性是Chk2 (Ki, 47 nM) 的 100倍。IC50 & Target Chk1 Chk2 CDK10.49 nM (Ki) 47 nM (Ki) 9.9 M (Ki)体外研究 PF 477736 (PF-00477736, 0.01-1 M) abrogates the camptothecin-induced DNA damage checkpoint in adose-dependent manner in CA46

5、cells. PF 477736 (180, 360, 540 nM) enhances gemcitabine-inducedcytotoxicity in a time- and dose-dependent manner in HT29 cells as determined by cell survival assay. PF477736 (360 nM) in combination with gemcitabine significantly decreases the phosphorylation of CDK1,consistent with checkpoint abrog

6、ation and cell entry into mitosis 1. PF 477736 (PF-00477736) poorlyinhibits CDK1 activity, with Ki of 9.9 M 1 2.体内研究 PF 477736 (PF-00477736, 4-60 mg/kg, i.p.) once a day (s.i.d.) or twice a day (b.i.d.) treatment alone exhibitsno antitumor activity in human colon Colo205 xenograft model. However, PF

7、 477736 dependently enhancesthe antitumor activity of a MTD of gemcitabine. PF 477736 (15 and 30 mg/kg) induces histone H3phosphorylation and DNA damage and increases apoptosis in Colo205 tumor samples from in vivo xenograftmodel 1.PROTOCOLCell Assay 1 HT29 or human umbilical vein endothelial cells

8、are treated with gemcitabine (15 nM) or camptothecin (25 nM)for 16 h. PF 477736 (PF-00477736) is subsequently added at varying concentrations. At 4 to 48 h after theaddition of PF 477736, the drug-containing medium is removed and cells are incubated in drug-free medium.When the vehicle-treated contr

9、ol cells are 90% confluent (8 days from plating), cells are harvested andcounted by Coulter counter 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Chemotherapy agents or PF 477736 (PF-00477736) are administered by i.p. injection when tumors ar

10、e 100Administration 1 to 150 mm3 in volume over the designated treatment schedules. Gemcitabine is administered over a rangeof doses including the maximum tolerated dose (MTD) in mice according to a once every 3 days for fourtreatments (q3d 4) schedule. PF 477736 is administered over a range of dose

11、s (4-60 mg/kg) according tothe q3d 4 schedule beginning 24 h after gemcitabine. MTD of PF 477736 is determined to be 40 mg/kgconsidering the severity of the behavioral response on i.p. administration and body weight loss of 5% to 10%.For cytotoxic agents, MTD is the occurrence of mean body weight lo

12、ss of 5% to 10% 1.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 Science. 2017 Dec 1;358(6367). Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemE Harvard Medical School LINCS LIBRARYSee mor

13、e customer validations on HYPERLINK / www.MedChemEREFERENCES1. Blasina A, et al. Breaching the DNA damage checkpoint via PF-00477736, a novel small-molecule inhibitor of checkpoint kinase 1. MolCancer Ther. 2008 Aug;7(8):2394-4042. Ashwell S, et al. Keeping checkpoint kinases in line: new selective inhibitors in clinical trials. Expert Opin Investig Drugs. 2008Sep;17(9):1331-40.Mce