CX-6258 HCl

製品コードS7041 バッチS704103

印刷

化学情報

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 (warmed with 50ºC water bath)

25 mg/mL (50.16 mM)

Ethanol (warmed with 50ºC water bath)

2 mg/mL (4.01 mM)

Water

Insoluble

体内（毎回新しく調製した物を用意してください）

Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	1.250mg/ml (2.51mM)	Taking the 1 mL working solution as an example, add 50 μL of 25 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

* <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
キナーゼアッセイ	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

参考

http://pubs.acs.org/doi/abs/10.1021/ml200259q

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。

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。