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CDKI-73
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。
CDKI-73图片
CAS NO:1421693-22-2
包装与价格：
包装价格(元)
2mg电议
5mg电议
10mg电议
50mg电议
100mg电议

产品介绍
CDKI-73 (LS-007) 是一种具有口服活性且高效的 CDK9 抑制剂，对 CDK9、CDK1 和 CDK2 的 Ki 值分别为 4 nM、4 nM 和 3 nM。
Cas No.1421693-22-2
别名LS-007
Canonical SMILESCNC1=NC(C)=C(C2=C(F)C=NC(NC3=CC(S(=O)(N)=O)=CC=C3)=N2)S1
分子式C15H15FN6O2S2
分子量394.45
溶解度DMSO : ≥ 52 mg/mL (131.83 mM);Water :< 0.1 mg/mL (insoluble)
储存条件Store at -20°C
General tipsFor obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.
Shipping ConditionEvaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request
产品描述

CDKI-73 is a potent CDK9 inhibitor with Ki of 4 nM; shows selective toxicity to CLL cells(LD50=80 nM) versus normal B cell and normal CD34+ cell(LD50>20 uM).IC50 value: 4 nM/80 nM(Ki/LD50) [1]Target: CDK9 inhibitorin vitro: CDKI-73 was cytotoxic to all of the CLL samples tested (n = 38) with a mean LD50 value of 0.08uM ± 0.10 uM following exposure to drug for 48h. In contrast, normal B-lymphocytes (n = 10) and CD34+ normal bone marrow cells (n = 5) were significantly less susceptible to the cytotoxic effects of CDKI-73. Treatment of CLL cells with 0.1 uM CDKI-73 for 4h inhibited the phosphorylation of cdk9 and ser2 of RNA polymerase II. CDKI-73 induces a rapid loss of MCL1 protein and this is mediated by significant inhibition at the level of gene transcription. However, this inhibition is not restricted to MCL1 as similar reductions in XIAP and CCND2 were also observed following exposure to CDKI-73 for 4h [1]. CDKI-73 rapidly inhibited cellular CDK9 kinase activity and down-regulated the RNAPII phosphorylation. CDK9 shRNA was also found to down-regulate the Mnk1 expression. Both CDKI-73 and CDK9 shRNA decreased anti-apoptotic proteins Mcl-1 and Bcl-2 and induced apoptosis [2]. in vivo: CDKI-73 exhibited a favorable pharmacokinetic profile with oral bioavailability of F = 56% following a single intravenous bolus dose at 2 mg/kg and an oral dose at 10 mg/kg in mice [1].

References:
[1]. Xie S, et al. Antitumor action of CDK inhibitor LS-007 as a single agent and in combination with ABT-199 against human acute leukemia cells. Acta Pharmacol Sin. 2016 Nov;37(11):1481-1489.
[2]. Lam F, et al. Targeting RNA transcription and translation in ovarian cancer cells with pharmacological inhibitor CDKI-73. Oncotarget. 2014 Sep 15;5(17):7691-704.