Home
Resources
Publications
Inhibition of Janus Kinases by Tyrosine Phosphorylation Inhibitor, Tyrphostin AG-490

Inhibition of Janus Kinases by Tyrosine Phosphorylation Inhibitor, Tyrphostin AG-490

Sajid Rashid, Nousheen Bibi, Zahida Parveen, Shagufta Shafique

J Biomol Struct Dyn. 2015;33(11):2368-79.

PMID: 26017266

Abstract:

Janus kinases (JAKs) belong to a crucial family of tyrosine kinases, implicated in the patho-physiology of multiple cancer types, and serve as striking therapeutic targets. To date, many potent, either ATP-competitive (PTK domain) or non-ATP-competitive JAK inhibitors have been identified. Among them, Tyrphostin AG-490 (2-cyano-3-(3,4-dihydroxyphenyl)-N-(phenylmethyl)-2-propenamide) is a well-known ATP-competitive inhibitor. However, its mode of action, details of interacting residues, and induced conformational changes in JAK-specific binding sites remain elusive. Here, through comparative structure analysis, molecular docking, and molecular dynamics simulation assays, we explored comparative binding patterns of AG-490 against JAK1, JAK2, and JAK3. Our results entail noteworthy observations about the binding affinity of AG-490 by illustrating distinctive amino acid residues lying at the conserved ATP-binding domains of JAK family members. By subsequent assessment of their structural homology and conserved structural folds, we highlight intriguing prospects to design more specific and potent inhibitors for selective targeting of JAK family members. Our comparative study provides a platform for the rational design of precise and potent inhibitor for selective targeting of JAK family members.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP133550308-B	Tyrphostin AG 490		133550-30-8	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: