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CCT245737 S-isomer
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
CCT245737 S-isomer图片
CAS NO:1489389-23-2
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW)379.34
FormulaC16H16F3N7O
CAS No.1489389-23-2(S-enantiomer);
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 75 mg/mL (197.7 mM)
Water: <1 mg/mL
Ethanol: 9 mg/mL (23.7 mM)
SMILES N#CC1=NC=C(NC2=NC=C(C(F)(F)F)C(NC[C@H]3CNCCO3)=C2)N=C1
SynonymsCCT 245737 S-enantiomer; CCT245737 S-isomer; CCT-245737.
实验参考方法
In Vitro

In vitro activity: CCT245737 is a potent inhibitor of recombinant human CHK1 with IC50 of 1.4±0.3 nM (mean±SD, n = 3, EZ Reader II assay). There is> 1,000-fold selectivity for CHK1 versus the functionally important kinases CDK1 and CHK2 (IC50=1.26-2.44 and 9.03 μM, respectively), and at least a 90-fold selectivity against cross-reacting kinases such as ERK8, PKD1, RSK1 and 2. CCT245737 potently inhibits cellular CHK1 activity (IC50 30-220nM) and enhances gemcitabine and SN38 cytotoxicity in multiple human tumor cell lines and human tumor xenograft models. It can abrogate an etoposide-induced G2/M arrest. CCT245737 has high cell permeability, as measured by transport across a CaCo2 cell monolayer.


Kinase Assay: CCT245737 shows<50% 10='' 121='' inhibition='' at='' m='' for='' representing='' a='' selectivity='' chk1='' of=''>5000-fold over these enzymes. Commercial in vitro 33P radiometric kinase assays are carried out against 124 human kinases using 10 μM CCT245737 at ATP concentrations corresponding to the kinase Km, ATP. Other kinase IC50 determinations for CHK2 and FLT3 are performed using a commercial assay or in-house with recombinant human CHK1 on a LabChip(R) EZ Reader II or CDK1 in a DELFIA assay.


Cell Assay: Cytotoxicity is determined as the drug concentration that gave 50% inhibition of tumor cell proliferation (GI50) using a 96h (i.e. 4-doublings) Sulforhodamine B (SRB) assay. Inhibition of intracellular CHK1 activity is measured using a cell based ELISA for the abrogation of an etoposide induced G2 checkpoint (mitosis induction assay, MIA).

In VivoMouse oral bioavailability is complete (100%) with extensive tumor exposure. CCT245737 shows significant single-agent activity against a MYC-driven mouse model of B-cell lymphoma. An i.v. dose of 10mg/kg CCT245737 into BALB/c mice gives a peak plasma concentration of 4μmol/L, with a half-life of 2.86h, an AUC0-∞ of 9.96μmol.h/L, a plasma clearance of 2.1L/h/kg and a large volume of distribution (0.19L). The equivalent oral dose gave an almost identical profile with an AUC0-∞ of 10.4μmol.h/L showing complete oral bioavailability (F = 105%). In a word, CCT245737 shows complete oral bioavailability with linear pharmacokinetics and high tumor/plasma ratios consistent with extensive tumor exposure. Adequate CCT245737 tumor drug exposure takes a significant antitumor activity.
Animal modelBALB/c mice
Formulation & DosageDissolved in DPTW (10% DMSO, 20% PEG400, 5% Tween 80 and 65% water) for oral vehicle; 10mg/kg(i.v.); 150mg/kg(p.o.); i.v. or p.o.
ReferencesOncotarget. 2016 Jan 19;7(3):2329-42.