CCT245737 (SRA737)

製品コードS8253 バッチS825302

印刷

化学情報

Chemical Structure Synonyms PNT-737 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C16H16F3N7O
分子量 379.34 CAS No. 1489389-18-5
Solubility (25°C)* 体外 DMSO 76 mg/mL warmed with 50ºC water bath (200.34 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 CCT245737 (SRA737) is an orally active CHK1 inhibitor with The IC50 of 1.4 nM. It exhibits >1,000-fold selectivity against CHK2 and CDK1.
in vitro 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[1].
in vivo Mouse 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[1].

プロトコル(参考用のみ)

細胞アッセイ 細胞株 The colon tumor cell lines HT29 and SW620, the pancreatic cancer cell line MiaPaCa-2 and the non-small cell lung cancer Calu6 cell line
濃度 --
反応時間 96 h
実験の流れ 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).
動物実験 動物モデル BALB/c mice
投薬量 10mg/kg(i.v.); 150mg/kg(p.o.)
投与方法 i.v. or p.o. administration

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Cancer-associated FBXW7 loss is synthetic lethal with pharmacological targeting of CDC7 [ Mol Oncol, 2023, 10.1002/1878-0261.13537] PubMed: 37866880
Regulation of CHK1 inhibitor resistance by a c-Rel and USP1 dependent pathway [ Biochem J, 2022, 479(19):2063-2086] PubMed: 36240066
Translational evidence for RRM2 as a prognostic biomarker and therapeutic target in Ewing sarcoma [ Mol Cancer, 2021, 20(1):97] PubMed: 34315482
CHK1 inhibition exacerbates replication stress induced by IGF blockade [ Oncogene, 2021, 10.1038/s41388-021-02080-1] PubMed: 34773074
Inhibition of Nuclear Pore Complex Formation Selectively Induces Cancer Cell Death [ Cancer Discov, 2020, CD-20-0581] PubMed: 32988961
Small Molecule Inhibitors and a Kinase-Dead Expressing Mouse Model Demonstrate That the Kinase Activity of Chk1 Is Essential for Mouse Embryos and Cancer Cells [ Life Sci Alliance, 2020, 3(8):e202000671] PubMed: 32571801
Checkpoint kinase-1 inhibition and etoposide exhibit a strong synergistic anticancer effect on chronic myeloid leukemia cell line K562 by impairing homologous recombination DNA damage repair [ Oncol Rep, 2020, 44(5):2152-2164] PubMed: 32901871

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。