Home
Resources
Publications
PF-06651600, a Dual JAK3/TEC Family Kinase Inhibitor

PF-06651600, a Dual JAK3/TEC Family Kinase Inhibitor

Hua Xu, Michael I Jesson, Uthpala I Seneviratne, Tsung H Lin, M Nusrat Sharif, Liang Xue, Chuong Nguyen, Robert A Everley, John I Trujillo, Douglas S Johnson, Gary R Point, Atli Thorarensen, Iain Kilty, etc.

ACS Chem Biol. 2019 Jun 21;14(6):1235-1242.

PMID: 31082193

Abstract:

PF-06651600 was developed as an irreversible inhibitor of JAK3 with selectivity over the other three JAK isoforms. A high level of selectivity toward JAK3 is achieved by the covalent interaction of PF-06651600 with a unique cysteine residue (Cys-909) in the catalytic domain of JAK3, which is replaced by a serine residue in the other JAK isoforms. Importantly, 10 other kinases in the kinome have a cysteine at the equivalent position of Cys-909 in JAK3. Five of those kinases belong to the TEC kinase family including BTK, BMX, ITK, RLK, and TEC and are also inhibited by PF-06651600. Preclinical data demonstrate that inhibition of the cytolytic function of CD8+ T cells and NK cells by PF-06651600 is driven by the inhibition of TEC kinases. On the basis of the underlying pathophysiology of inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease, alopecia areata, and vitiligo, the dual activity of PF-06651600 toward JAK3 and the TEC kinase family may provide a beneficial inhibitory profile for therapeutic intervention.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
ALP1792180814	PF-06651600		1792180-81-4 (free base)	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: