Selective targeting of the inactive state of hematopoietic cell kinase (Hck) with a stable curcumin derivative.

ABSTRACT: Hck, a Src family nonreceptor tyrosine kinase (SFK), has recently been established as an attractive pharmacological target to improve pulmonary function in COVID-19 patients. Hck inhibitors are also well known for their regulatory role in various malignancies and autoimmune diseases. Curcumin has been previously identified as an excellent DYRK-2 inhibitor, but curcumin's fate is tainted by its instability in the cellular environment. Besides, small molecules targeting the inactive states of a kinase are desirable to reduce promiscuity. Here, we show that functionalization of the 4-arylidene position of the fluorescent curcumin scaffold with an aryl nitrogen mustard provides a stable Hck inhibitor (K_d = 50 ± 10 nM). The mustard curcumin derivative preferentially interacts with th

SUBMITTER: Chakraborty MP 

PROVIDER: S-EPMC7946438 | biostudies-literature | 2021 Jan-Jun

REPOSITORIES: biostudies-literature