product name LDC000067
Description: LDC000067 (also called LDC067) is a novel highly selective CDK9 inhibitor with IC50 of 44 nM. LDC000067 exhibited selectivity for CDK9 over other CDKs in the range of 55-fold (vs. CDK2) to over 230-fold (vs. CDK6 and CDK7). LDC067 also inhibited transcription in a dose-dependent and ATP-competitive manner. In whole cells, LDC000067 induced the tumor suppressor protein p53 activation and apoptosis. LDC000067 also selectively reduced short-lived mRNAs, including those that encode regulators of apoptosis and proliferation such as MYC and MCL1.
References: Br J Pharmacol. 2014 Jan;171(1):55-68
370.43
Formula
C18H18N4O3S
CAS No.
1073485-20-7
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 74 mg/mL (199.8 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Synonyms
LDC067
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19405910
| In Vitro |
In vitro activity: LDC000067 reduces Ser2-P, induces p53 activation and leads to apoptosis in mESCs. In addition, LDC067 also dose-dependently inhibits P-TEFb-dependent de novo RNA synthesis of cellular genes. Kinase Assay: Kinase inhibition by LDC000067 was measured in a radio metric assay, which directly measured kinase catalytic activity towards a specific substrate. Briefly, 10 μM LDC000067 or DMSO as solvent control, were added to base reaction buffer (10 mM MgCl2, 1 mM EDTA, 20 mM HEPES pH 7.5, 2 mM DTT, 0.02 mg·mL-1 BSA, 0.1 mM Na3VO4, 0.02% Brij35, 1% DMSO), containing cofactors and substrates, which were required by the individual kinase. 10 μCi of [γ-33P]-APP (10mCi·mL-1, 3000Ci·mmol-1, Perkin Elmer) was added to the reaction mixture. And such kinase reaction incubated for 120min at room temperature. Reactions were found on P81 ion exchange paper, and filters generally washed in 0.75% phosphoric acid before radiometric quantification. Each protein kinase was measured in duplicate, and its catalytic activity expressed as residual kinase activity, which shows the percentage of average substrate phophorylation in contrast with the solvent control reaction. Cell Assay: LDC000067 inhibits CDK9 with an IC50 value of 44(10 nM, and its selectivity for CDK9 over other CDKs is in the range of 55-fold to over 230-fold, especially higher selectivity in an ATP-competitive kinase binding assay. Besides, effects of LDC000067 in whole cells contain induction of the tumour suppressor protein p53 and apoptosis. Moreover, gene expression profiling of cells treated with LDC000067 demonstrate selective reduction of short-lived mRNAs, which encode regulators of proliferation and apoptosis, such as MCL1 and MYC. |
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| In Vivo | |
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| Formulation & Dosage | Br J Pharmacol. 2014 Jan;171(1):55-68. |
| References |
