CX-6258 HCl

製品コードS7041 バッチS704103

印刷

化学情報

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

C26H24ClN3O3.HCl
分子量 498.40 CAS No. 1353859-00-3
Solubility (25°C)* 体外 DMSO 25 mg/mL warmed with 50ºC water bath (50.16 mM)
Ethanol 2 mg/mL warmed with 50ºC water bath (4.01 mM)
Water 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 CX-6258 HCl is a potent, orally efficacious pan-Pim kinase inhibitor with IC50 of 5 nM, 25 nM and 16 nM for Pim1, Pim2, and Pim3, respectively.
in vitro CX-6258 shows antiproliferative activity against a panel of human cancer cell lines with IC50 of 0.02-3.7 μM, mostly sensitive to acute leukemia cell lines. Combinations of CX-6258 with doxorubicin (10:1 molar ratio) and CX-6258 with paclitaxel (100:1 molar ratio) produces synergistic cell killing with combination index (CI50) values equal to 0.4 and 0.56, respectively. CX-6258 causes dose dependent inhibition of the phosphorylation of two pro-survival proteins, Bad and 4E-BP1, at the Pim kinase specific sites S112 and S65 and T37/46, respectively. [1]
in vivo CX-6258 exhibits dose dependent efficacy in suppressing tumor growth in mice carrying MV-4-11 xenografts, with a 50 mg/kg dose producing 45% tumor growth inhibition (TGI) and a 100 mg/kg dose producing 75% TGI [1]

プロトコル(参考用のみ)

キナーゼアッセイ Pim activity assay
Pim-1 and Pim-2 inhibitions are measured in radiometric assays using human recombinant Pim-1 at [ATP] = 30 μM (substrate RSRHSSYPAGT) and human recombinant Pim-2 at [ATP] = 5 μM (substrate RSRHSSYPAGT). The radiometric assay for Pim-3 uses RSRHSSYPAGT as a substrate in the presence of [ATP] = 155 μM.
細胞アッセイ 細胞株 ALL, AML, CML, PML and MM cell lines
濃度 ~10 μM
反応時間 96 hours
実験の流れ
動物実験 動物モデル Acute myeloid leukemia xenografts MV-4-11
投薬量 100 mg/kg
投与方法 Orally daily

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：

Oncogenic PKA signaling increases c-MYC protein expression through multiple targetable mechanisms [ Elife, 2023, 12e69521] PubMed: 36692000
A Single-Cell Landscape of High-Grade Serous Ovarian Cancer [ Nat Med, 2020, 10.1038/s41591-020-0926-0] PubMed: 32572264
Targeting codon 158 p53-mutant cancers via the induction of p53 acetylation. [ Nat Commun, 2020, 29;11(1):2086] PubMed: 32350249
Anti-platelet Properties of Pim Kinase Inhibition Is Mediated Through Disruption of Thromboxane A2 Receptor Signalling [ Haematologica, 2020, 28;haematol.2019.223529] PubMed: 32467143
Thioguanine Induces Apoptosis in Triple-Negative Breast Cancer by Regulating PI3K-AKT Pathway [ Front Oncol, 2020, 10:524922] PubMed: 33194583
PIM1 inhibitor synergizes the anti-tumor effect of osimertinib via STAT3 dephosphorylation in EGFR-mutant non-small cell lung cancer. [ Ann Transl Med, 2020, 8(6):366] PubMed: 32355810
Pan-PIM kinase inhibitors enhance Lenalidomide's anti-myeloma activity via cereblon-IKZF1/3 cascade [ Cancer Lett, 2019, 440-441:1-10] PubMed: 30312729
Global survey of cell death mechanisms reveals metabolic regulation of ferroptosis [ Nat Chem Biol, 2016, 12(7):497-503] PubMed: 27159577
Pim1 kinase regulates c-Kit gene translation. [An N, et al. Exp Hematol Oncol, 2016, 10.1186/s40164-016-0060-3] PubMed: 28042518

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。

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