CCT244747 is a novel potent, highly selective, orally active ATP-competitive CHK1 inhibitor with potential anticancer activity,

>98%

Store at -20℃ for one year（Powder）；Store at 2-4℃ for two weeks；Store at -20℃ for six months after dissolution.

CCT-244747, CCT 244747

solid powder

10 mM in DMSO

Checkpoint Kinase (Chk)

CCT244747 poorly inhibits CHK2 (IC50 >10 μM) and CDK1 (IC50 >10 μM). CCT244747 has potent activities against CHK1, RSK1, RSK2, AMPK, BRSK1, IRAK1,and TrkA, with >80% inhibition. CCT244747 (10 μM) exhibits . CCT244747 inhibits FLT3 with an IC50 of 600 nM. CCT244747 (0.5 μM) overcomes genotoxic-induced S and G2 cell cycle arrest in human colon cancer cell lines. CCT244747 inhibits cellular CHK1 function with IC50s ranging from 29 nM to 170 nM for cellular G2 checkpoint abrogation (MIA, mitosis induction assay) in HT29, SW620, MiaPaCa-2, and Calu6 cell lines; the GI50s are between 0.33 and 3μM. CCT244747 (0.3 μM) inhibits SN38 and gemcitabine-induced CHK1 activity in HT29 and SW620 colon cancer cell lines and this correlates with abrogation of cell cycle arrest, induction of DNA damage and apoptosis. CCT244747 (0.5-2.0 μM) increases the sensitivity of bladder and head and neck cancer cell lines (T24, RT112 and Cal27) to radiation.

CCT244747 (100 mg/kg po, qd7d) significantly reduces tumor burden in human tumor xenografts. CCT244747 (100-300 mg/kg, po) inhibits gemcitabine-induced pS296 CHK1 for up to 24 h in HT29 colon tumor xenografts. CCT244747 (75 mg/kg, p.o.) in combination with gemcitabine has potent antitumor effects in HT29 colon tumor xenografts and Calu6 human lung cancer xenografts. CCT244747 (150 mg/kg p.o.) also shows antitumor activities with irinotecan in SW620 human colon tumor xenografts. CCT244747 (100 mg/kg, p.o.) exhibits radiosensitization activity in Cal27 xenografts.

CCT251236 is an orally available pirin ligand from a heat shock transcription factor 1 (hsf1) phenotypic screen with an IC50 of 19 nM for inhibition of HSF1-mediated HSP72 induction.

98%

Store at -20℃ for one year（Powder）；Store at 2-4℃ for two weeks；Store at -20℃ for six months after dissolution.

DMSO : ≥ 150 mg/mL (271.43 mM)

CCT251236 displays the desired balance of in vitro properties, while maintaining excellent cellular activity with an IC50 of 19 nM. The free GI50 in SK-OV-3 cells is 1.1 nM. Western blotting confirms that CCT251236 blocks the HSF1-mediated induction of both HSP72 and HSP27 as representative heat shock proteins, following treatment with the HSP90 inhibitor 17AAG. Also, qPCR analysis demonstrates that CCT251236 inhibits the induction of HSP72 at the mRNA level, clearly blocking the induction of HSPA1A gene expression with an IC50 of 40 nM.

CCT251236 displays the desired balance of in vitro properties, while maintaining excellent cellular activity with an IC50 of 19 nM. The free GI50 in SK-OV-3 cells is 1.1 nM. Western blotting confirms that CCT251236 blocks the HSF1-mediated induction of both HSP72 and HSP27 as representative heat shock proteins, following treatment with the HSP90 inhibitor 17AAG. Also, qPCR analysis demonstrates that CCT251236 inhibits the induction of HSP72 at the mRNA level, clearly blocking the induction of HSPA1A gene expression with an IC50 of 40 nM.

CCT128930 is a potent, ATP-competitive and selective inhibitor of Akt2 with IC50 of 6 nM, 28-fold greater selectivity for Akt2 than the closely related PKA kinase.

98%

Store at -20℃ for one year（Powder）；Store at 2-4℃ for two weeks；Store at -20℃ for six months after dissolution.

DMSO ：68 mg/mL (198.92 mM)

Akt2 ,p70 S6K ,PKA

CCT128930 exhibits marked antiproliferative activity against PTEN-deficient human tumor cell lines including U87MG human glioblastoma cells, LNCaP human prostate cancer cells and PC3 human prostate cancer cells with GI50 of 6.3 μM, 0.35 μM and 1.9 μM, respectively. Furthermore, CCT128930 causes a G1 arrest in PTEN-null U87MG human glioblastoma cells and Akt pathway blockade.

CCT128930 at 25 mg/kg i.p. shows a marked antitumor effect in established PTEN-null U87MG human glioblastoma xenografts with a treated:control (T/C) ratio of 48% on day 12. In HER2-positive, PIK3CA-mutant BT474 human breast cancer xenografts, CCT128930 at 40 mg/kg also produces a profound antitumor effect with complete growth arrest and a T/C ratio of 29% on day 22. CCT128930 administrated via i.v. reaches a peak concentration of 6.4 μM in plasma and is eliminated with a relatively short half-life, high volume of distribution, and rapid clearance, giving an area under the curve AUC0-∞ of 4.6 μM h. CCT128930 administrated via i.p. leads to the peak plasma drug concentration of 1.3 μM and the corresponding AUC0-∞ of 1.3 μM·h. Oral CCT128930 administration leads to the peak plasma concentration of only 0.43 μM and a correspondingly low AUC0-∞ of 0.4 μM·h.

1. Yap TA, et al. Mol Cancer Ther. 2011, 10(2), 360-371.

CCT129202是一种ATP竞争性的pan-Aurora抑制剂，作用于Aurora A，Aurora B和Aurora C时，IC50分别为0.042 μM，0.198 μM和0.227 μM，对FGFR3， GSK3β， PDGFRβ等作用效果稍弱。CCT129202是ATP竞争性抑制剂，作用于重组Aurora A激酶时Ki为49.8 nM。1 μM CCT129202高度选择性作用于Aurora A和Aurora B，抑制分别达92%和60%, 轻微抑制FGFR3，抑制达27%, 但是不抑制CRAF。CCT129202作用于人类肿瘤细胞系，抑制增殖，GI50值为从作用于MV4-11的0.08 μM 到作用于MDA-MB-157的1.7 μM。

98%

Store at -20℃ for one year（Powder）；Store at 2-4℃ for two weeks；Store at -20℃ for six months after dissolution.

CCT-129202

DMSO ：3 mg/mL (6.03 mM)

Enhancing Chemosensitivity in ABCB1- and ABCG2-Overexpressing Cells and Cancer Stem-like Cells by An Aurora Kinase Inhibitor CCT129202.
Cheng C,et al. Mol Pharm. 2012 Jun 13. PMID: