1073485-20-7

Basic information

• Product Name: LDC000067
• Synonyms: LDC000067;LDC 067;LDC067;LDC-067;(3-(6-(2-Methoxyphenyl)pyrimidin-4-ylamino)phenyl)methanesulfonamide;3-[[6-(2-methoxyphenyl)-4-pyrimidinyl]amino]-benzenemethanesulfonamide
• CAS NO: 1073485-20-7
• Molecular Formula: C₁₈H₁₈N₄O₃S
• Molecular Weight: 370.43
• Product Categories: Inhibitors
• Mol File: 1073485-20-7.mol
• Article Data: 2

Chemical Properties

• Boiling Point: 604.1±65.0 °C(Predicted)
• Appearance: /
• Density: 1.360±0.06 g/cm3(Predicted)
• Storage Temp.: under inert gas (nitrogen or Argon) at 2–8 °C
• Solubility: insoluble in H2O; insoluble in EtOH; ≥18.52 mg/mL in DMSO
• PKA: 10.27±0.60(Predicted)
• CAS DataBase Reference: LDC000067(CAS DataBase Reference)
• NIST Chemistry Reference: LDC000067(1073485-20-7)
• EPA Substance Registry System: LDC000067(1073485-20-7)

Safety Data

• Hazardous Substances Data: 1073485-20-7(Hazardous Substances Data)

Usage

Biological Activity

ldc000067 (ldc067) is a novel specific inhibitor of cdk9 with ic50 value of 44 ± 10 nm [1].cyclin-dependent kinase 9 (cdk9) is a cyclin-dependent kinase. cdk9 and cyclin t form the positive transcription elongation factor b (p-tefb) complex for rna polymerase ii and functions by phosphorylating the c-terminal domain of the largest subunit of rna polymerase ii [1].ldc000067 (ldc067) is a novel and highly specific cdk9 inhibitor. 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 [1].

references

[1]. albert tk, rigault c, eickhoff j, et al. characterization of molecular and cellular functions of the cyclin-dependent kinase cdk9 using a novel specific inhibitor. br j pharmacol, 2014, 171(1): 55-68.

Upstream product

• 344750-15-8 (3-aminophenyl)methanesulfonamide 
• 75634-03-6 4-chloro-6-(2-methoxy-phenyl)-pyrimidine 

Relevant articles and documents

Characterization of molecular and cellular functions of the cyclin-dependent kinase CDK9 using a novel specific inhibitor

Background and Purpose The cyclin-dependent kinase CDK9 is an important therapeutic target but currently available inhibitors exhibit low specificity and/or narrow therapeutic windows. Here we have used a new highly specific CDK9 inhibitor, LDC000067 to interrogate gene control mechanisms mediated by CDK9. Experimental Approach The selectivity of LDC000067 was established in functional kinase assays. Functions of CDK9 in gene expression were assessed with in vitro transcription experiments, single gene analyses and genome-wide expression profiling. Cultures of mouse embryonic stem cells, HeLa cells, several cancer cell lines, along with cells from patients with acute myelogenous leukaemia were also used to investigate cellular responses to LDC000067. Key Results The selectivity of LDC000067 for CDK9 over other CDKs exceeded that of the known inhibitors flavopiridol and DRB. LDC000067 inhibited in vitro transcription in an ATP-competitive and dose-dependent manner. Gene expression profiling of cells treated with LDC000067 demonstrated a selective reduction of short-lived mRNAs, including important regulators of proliferation and apoptosis. Analysis of de novo RNA synthesis suggested a wide ranging positive role of CDK9. At the molecular and cellular level, LDC000067 reproduced effects characteristic of CDK9 inhibition such as enhanced pausing of RNA polymerase II on genes and, most importantly, induction of apoptosis in cancer cells. Conclusions and Implications Our study provides a framework for the mechanistic understanding of cellular responses to CDK9 inhibition. LDC000067 represents a promising lead for the development of clinically useful, highly specific CDK9 inhibitors.