443798-47-8

Usage

Uses

Used in Cancer Therapy:
CDK1/2 inhibitor III is used as an anticancer agent for its inhibitory activities against Cdk1 and Cdk2, which are key regulators of cell cycle progression. It effectively blocks the growth of several cancer cell lines, with IC50 values ranging from 20 to 92 nM, and less potently inhibits CDC2-like kinases 1 and 3, VEGFR2, and GSK-3β.
Used in Drug Development:
CDK1/2 inhibitor III is used in the development of pharmaceuticals targeting cancer cells. Its ability to inhibit the growth of various human tumor cells makes it a valuable tool in the discovery and optimization of new cancer therapies.

in vitro

cdk1/2 inhibitor iii was identified as a cell-permeable inhibitor of cdk1/cyclin b and cdk2/cyclin a and could less potently inhibit cdc2-like kinases 1 and 3, vegfr2, and gsk-3β. cdk1/2 inhibitor iii was found to be lack of effect against a panel of other kinases. moreover, cdk1/2 inhibitor iii could block the growth of various cancer cell lines (ic50 values range from 20 to 92 nm) [1].

in vivo

the in-vivo efficacy of compound 3b, a structurally close cdk1/2 inhibitor iii analog, was examined in the a375 human melanoma cell xenograft model. doses at 125, 100, and 75 mg/kg were administered once a day for 32 days and tumor size was measured every 4 days. the results showed that in the 125 mg/kg group, there was one nontreatment-related death but the remaining four animals experienced stable disease. in addition, compound 3b administered at 100 and 75 mg/kg led to mean day of survival values of 50.1 and 48.5 days, respectively, with only one treatment-related death in the 100 mg/kg group [1].

IC 50

0.6 and 0.5 nm forcdk1/cyclin b and cdk2/cyclin a, respectively

references

[1] lin, r. ,connolly, p.j.,huang, s., et al. 1-acyl-1h-[1,2,4]triazole-3,5-diamine analogues as novel and potent anticancer cyclin-dependent kinase inhibitors: synthesis and evaluation of biological activities. journal of medicinal chemistry 48(13), 4208-4211 (2005).

Upstream product

• 443799-31-3 4-((5-amino-1H-1,2,4-triazol-3-yl)amino)benzenesulfonamide 
• 207974-17-2 2,6-difluorophenylisothiocyanate 
• 700805-72-7 phenyl-N'-cyano-N-(4-sulfamoylphenyl)carbamimidate 
• 51908-29-3 4-isothiocyanatobenzene sulfonamide 
• 443799-30-2 4-{3-[(3,5-dimethyl-pyrazol-1-yl)-imino-methyl]-thioureido}-benzenesulfonamide 
• 63-74-1 sulfanilamide 

Relevant academic research and scientific papers

In silico Screening and Evaluation of Plasmodium falciparum Protein Kinase 5 (PK5) Inhibitors

An in silico screen of 350 000 commercially available compounds was conducted with an unbiased approach to identify potential malaria inhibitors that bind to the Plasmodium falciparum protein kinase 5 (PfPK5) ATP-binding site. PfPK5 is a cyclin-dependent kinase-like protein with high sequence similarity to human cyclin-dependent kinase 2 (HsCDK2), but its precise role in cell-cycle regulation remains unclear. After two-dimensional fingerprinting of the top scoring compounds, 182 candidates were prioritized for biochemical testing based on their structural diversity. Evaluation of these compounds demonstrated that 135 bound to PfPK5 to a similar degree or better than known PfPK5 inhibitors, confirming that the library was enriched with PfPK5-binding compounds. A previously reported triazolodiamine HsCDK2 inhibitor and the screening hit 4-methylumbelliferone were each selected for an analogue study. The results of this study highlight the difficult balance between optimization of PfPK5 affinity and binding selectivity for PfPK5 over its closest human homologue HsCDK2. Our approach enabled the discovery of several new PfPK5-binding compounds from a modest screening campaign and revealed the first scaffold to have improved PfPK5/HsCDK2 selectivity. These steps are critical for the development of PfPK5-targeting probes for functional studies and antimalarials with decreased risks of host toxicity.

1-Acyl-1H-[1,2,4]triazole-3,5-diamine analogues as novel and potent anticancer cyclin-dependent kinase inhibitors: Synthesis and evaluation of biological activities

A series of 1-acyl-1H-[1,2,4]triazole-3,5-diamine analogues were synthesized as cyclin-dependent kinase (CDK) inhibitors. These compounds showed potent and selective CDK1 and CDK2 inhibitory activities and inhibited in vitro cellular proliferation in various human tumor cells. Representative compound 3b demonstrated in vivo efficacy in a human melanoma A375 xenograft model in nude mice.

Substituted triazole diamine derivatives as kinase inhibitors

The present invention provides substituted triazole diamine derivatives as selective kinase or dual-kinase inhibitors and a method for treating or ameliorating a selective kinase or dual-kinase mediated disorder.