853299-07-7

Usage

Biological Activity

k03861 is a type ii inhibitor of cdk2. the cyclin-dependent kinase holoenzymes contain a catalytic subunit, the cdk, a family of regulatory subunits, and the cyclins. cdks are the catalytic subunits of the mammalian heterodimeric serine/threonine kinases progression, cyclin-dependent kinases (cdks) play important roles in the cell cycle regulation, transcription, and neuronal function. cdks are frequently deregulated in some human tumours. the inhibitors targeted cdk are thought to prevent cell proliferation regulating cyclin-cdk complexes. the central role of cdks in cell cycle regulation makes them a promising target for studying inhibitory molecules that can modify the cell proliferation [1].k03861 is an aminopyrimidine-phenyl urea inhibitor of cdk2. the type ii inhibitor cdk2 cocrystal structure of cdk2 with the inhibitor k03861 revealed a canonical type ii binding mode. the type ii inhibitors could compete with the binding of cyclins. the residues important for the type ii inhibitors may be distant to the atp binding pockets. the crystal structure of this complex may provide a foundation for the cyclin-competitive cdk2 inhibitors [2].

references

malumbres m, barbacid m. mammalian cyclin-dependent kinases[j]. trends in biochemical sciences, 2005, 30(11): 630-641.alexander l t, mobitz h, drueckes p, et al. type ii inhibitors targeting cdk2[j]. acs chemical biology, 2015, 10(9): 2116-2125.

Upstream product

• 709045-30-7 2,2,2-trifluoro-N-[4-(4-methyl-piperazin-1-ylmethyl)-3-trifluoromethyl-phenyl]-acetamide 
• 853298-46-1 4-(4-nitro-phenoxy)-pyrimidin-2-ylamine 
• 694499-26-8 4-(4-methylpiperazin-1-ylmethyl)-3-trifluoromethylaniline 
• 417724-26-6 4-(4-amino-phenoxy)-pyrimidin-2-ylamine 
• 54840-15-2 4-N-tert-butoxycarbonylaminophenol 
• 876322-73-5 4-amino-2-(trifluoromethyl)benzaldehyde 
• 654-70-6 4-amino-2-trifluoromethylbenzonitrile 

Downstream Products

• 853299-06-6 1-[4-(2-acetylamino-pyrimidin-4-yloxy)-phenyl]-3-[4-(4-methyl-piperazin-1-ylmethyl)-3-trifluoromethyl-phenyl]-urea 

Relevant academic research and scientific papers

Syntheses of a triad of Flt3 kinase inhibitors: From bench to pilot plant

We have designed and developed an alternative synthesis for the manufacturing of a triad of Flt3 kinase inhibitors (AST487, ATH686, and AUZ454) to support clinical assessments of patients with Flt3-dependent tumor diseases. The new synthesis is convergent

DIARYL UREA DERIVATIVES IN THE TREATMENT OF PROTEIN KINASE DEPENDENT DISEASES

The invention relates to the use of diaryl urea derivatives for the manufacture of pharmaceutical compositions for the treatment of RET dependent disorders, especially RET dependent tumor diseases. The invention further relates to novel N-[4-(pyrimidin-4-yloxy)-phenyl]-N’-phenyl-urea derivatives and their use in the treatment of the animal or human body, especially in the treatment of a protein kinase dependent disease, to pharmaceutical compositions comprising such novel N-[4-pyrimidin-4-yloxy)-phenyl]-N’-phenyl-urea derivatives and to the use of such novel N-[4-(pyrimidin-4-yloxy)-phenyl]-N’-phenyl-urea derivatives for the preparation of pharmaceutical compositions for use in the treatment of protein kinase dependent diseases, especially of proliferative diseases, such as tumour diseases.