A-770041

Inhibitor of LCK

Structure

Information

  • LCK
  • Inhibitor
  • 1-10 uM
  • Reviewer recommended concentration: Potentiation of paclitaxel and doxorubicin was tested using 4 nM-10 uM in U-2OSMR and KHOSR2.

In Vitro Validations

Uniprot ID: P06239
Target Class: Kinase
Target SubClass: TK
Potency: IC50
Potency Value: 147 nM @ 1 mM ATP
Potency Assay: Enzymatic inhibition assay
PDB ID for probe-target interaction (3D structure): 2C0O
Structure-activity relationship: yes
Target aliases:
Tyrosine-protein kinase Lck, LCK, LCK_HUMAN, LSK, ...

DOI Reference: 10.1016/j.bmcl.2005.09.039

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Probe Selectivity in Vitro:

A-770041 is 300-fold selective against Fyn, the other Src-family kinase involved in T-cell signaling. A-770041 exhibits >60-fold selectivity versus the Src and Fgr, and >8-fold versus Lyn and Hck. Selectivity against the receptor tyrosine kinases Tie-2 and Kdr was >340-fold. (Src 9.1, Fgr 14.1, Fyn 44.1 uM); Selective over ZAP-70, ITK and PKC

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SERP ratings and comments


SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

This is a selective probe within the src family of RTK’s as described. Selectivity outside this family has been mentioned, but data not provided. From JPET paper: “A-770041 is 60-fold selective against Src, 95-fold selective against Fgr, and 300-fold selective against Fyn. A-770041 was also greater than 200-fold selective against a secondary battery of approximately 20 serine/threonine and tyrosine kinases outside of the Src family and IC50 values greater than 10 uM in a CEREP panel of approximately 70 molecular targets (data not shown).”

(last updated: 18 Dec 2020 )

SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

Initial studies involving development and medicinal chemistry were performed against purified proteins (including selectivity panels) and in vivo in rats and mice. Two later studies used this probe in cells to potentiate chemotherapies, in which case a range of concentrations were tested, and to target an acute myeloid leukemia cell line known to have a mutant dysregulated Lck protein. The latter studies provide good evidence for cellular engagement of the target in a selective way.

(last updated: 19 Jan 2021 )

SERP Ratings

In Cell Rating
In Model Organisms

(last updated: 29 Mar 2021 )