LDC000067

LDC000067 is a highly specific CDK9 inhibitor with an IC50 value of 44±10 nM in vitro.

Research Areas >> Cancer

CDK9- Cyclin T1:44 nM (IC50)

cdk2-cyclin A:2441 nM (IC50)

cdk1-cyclin B1:5513 nM (IC50)

cdk4-cyclin D1:9242 nM (IC50)

GSK3A:1460 nM (IC50)

HGK/MAP4K4:820 nM (IC50)

ABL2/ARG:3640 nM (IC50)

The selectivity of LDC000067 for CDK9 over other CDKs exceeds that of the known inhibitors flavopiridol and DRB. LDC000067 displayed 55/125/210/ >227/ >227-fold selectivity for CDK9 versus CDK2/1/4/6/7. LDC000067 inhibits in vitro transcription in an ATP-competitive and dose-dependent manner. Gene expression profiling of cells treated with LDC000067 demonstrates a selective reduction of short-lived mRNAs, including important regulators of proliferation and apoptosis[1].

The fluorescence resonance energy transfer (FRET)-based LANCE Ultra KinaSelect Ser/Thr kit is used to determine IC50 values for various CDK inhibitors. Briefly, a specific ULight MBP peptide substrate (50 nM final concentration) is phosphorylated by a CDK-cyclin pair in buffer (50 mM HEPES-KOH pH 7.5, 10 mM MgCl2, 1 mM EGTA, 2 mM dithiothreitol) containing ATP at the concentration of the Km values of the individual kinases for 1 h at room temperature. Subsequently, phosphorylation is detected by addition of specific Eu-labelled anti-phospho-antibodies (2 nM), which upon binding to the phosphopeptide give rise to a FRET signal. FRET signals are then recorded[1].

[1]. Albert TK, et al. Characterization of molecular and cellular functions of the cyclin-dependent kinase CDK9 using a novel specific inhibitor. Br J Pharmacol. 2014 Jan;171(1):55-68.

Abemaciclib(LY2835219) | Ribociclib (LEE011) | Dinaciclib (SCH727965) | THZ1 2HCl | Roscovitine (CYC202) | THZ531 | RO-3306 | Flavopiridol | NVP 2 | BAY-1143572 Racemate | CYC-065 | AZD5438 | BIO | Kenpaullone | SNS-032 (BMS-387032)