1619903-54-6

Basic information

• Product Name: LY2857785
• Synonyms: LY2857785
• CAS NO: 1619903-54-6
• Molecular Formula: C26H36N6O
• Molecular Weight: 448.60364
• Mol File: 1619903-54-6.mol
• Article Data: 1

Chemical Properties

• Boiling Point: 671.0±65.0 °C(Predicted)
• Appearance: /
• Density: 1.29±0.1 g/cm3(Predicted)
• Storage Temp.: 2-8°C(protect from light)
• Solubility: insoluble in H2O; ≥13.87 mg/mL in EtOH with gentle warming; ≥2.63 mg/mL in DMSO with gentle warming and ultrasonic
• PKA: 10.05±0.40(Predicted)
• CAS DataBase Reference: LY2857785(CAS DataBase Reference)
• NIST Chemistry Reference: LY2857785(1619903-54-6)
• EPA Substance Registry System: LY2857785(1619903-54-6)

Safety Data

• Hazardous Substances Data: 1619903-54-6(Hazardous Substances Data)

Usage

Uses

LY2857785 is a CDK9 inhibitor.

Biological Activity

ly2857785 was identified as a type i reversible and competitive atp kinase inhibitor against cdk9 and other transcription kinases cdk8 and cdk7.[1,2]cdk7 acts as a cdk-activating kinase and regulate transcription. cdk8 and cdk9 regulate transcription via phosphorylation of the rna polymerase ii carboxyl terminal domain. the cdk9-related pathway performs an important role in several biological processes, such as cell growth, proliferation, protection from apoptosis and differentiation. these kinases are reported dys-regulation in some cancers. [2]transcription activation requires phosphorylation of a carboxyl-terminal domain, by a variety of kinases including cdk7, cdk8, and cdk9. by inhibiting these kinases, ly2857785 has unique transcription inhibitor activity. ly2857785 dramatically inhibited xiap protein level in mv-4-11 and other hematologic cancer cells. it also can significantly reduce rnap ii ctd phosphorylation and dramatically decreases mcl1 protein levels to result in apoptosis in a variety of leukemia and solid tumor cell lines. [1]ly2857785 potently inhibits a carboxyl-terminal domain phosphorylation and exhibits antitumor ef?cacy in orthotopic models of leukemia. ly2857785 inhibits the growth of leukemia cells, including orthotopic leukemia preclinical models as well as in ex vivo acute myeloid leukemia and chronic lymphocytic leukemia patient tumor samples. ly2857785 may be used in treating patients with hematologic tumors, particularly aml and cll. [1]

references

[1] yin t, lallena mj, kreklau el etal. , a novel cdk9 inhibitor shows potent antitumor efficacy in preclinical hematologic tumor models. mol cancer ther. 2014 jun;13(6):1442-56.[2] romano g1, giordano a. role of the cyclin-dependent kinase 9-related pathway in mammalian gene expression and human diseases. cell cycle. 2008 dec;7(23):3664-8.

Upstream product

• 1823787-20-7 2‐(5‐bromo‐2‐methyl‐2H‐indazol‐3‐yl)propan‐2‐ol 
• 465529-56-0 2-Methyl-5-bromo-2H-indazole 
• 29943-42-8 Tetrahydro-4H-pyran-4-one 

Downstream Products

• 1619903-55-7 N₁-[4-(3-isopropyl-2-methyl-2H-indazol-5-yl)pyrimidin-2-yl]-N₄-(tetrahydro-2H-pyran-4-yl)cyclohexane-trans-1,4-diamine methanesulfonic acid salt 

Relevant articles and documents

For synthesizing CDK9 inhibitors of key intermediate and its preparation and use

The invention relates to a key intermediate for preparation of a CDK9 inhibitor, a synthesis method thereof and a method for preparation of the CDK9 inhibitor with the intermediate, especially a method for synthesis of LY2857785. The starting raw materials and reaction reagents of the synthesis method are cheap and easily available, the reaction conditions of the whole synthesis route are mild, and the yield is high. (synthesis process shown as the specification).