Cambridge Open Engage home
What is Cambridge Open Engage?
How to Submit
Browse
About
News [opens in a new tab]

A Chemical Probe for Dark Kinase STK17B Derives its Potency and High Selectivity Through a Unique P-loop Conformation

07 July 2020, Version 1

Abstract

We present the discovery of thieno[3,2-d]pyrimidine SGC-STK17B-1 (11s), a high-quality chemical probe for this understudied “dark” kinase. 11s is an ATP-competitive inhibitor that showed remarkable selectivity over other kinases including the closely related STK17A. X-ray crystallography of 11s and related thieno[3,2-d]pyrimidines bound to STK17B revealed a unique P-loop conformation characterized by a salt bridge between R41 and the carboxylic acid of the inhibitor.

Keywords

kinase
Chemical Probe
X-ray crystal structure determination
Molecular Dynamics Simulation Study

Supplementary materials

Title
Description
Actions
Title
SI File 1
Description
Actions
Title
SI File 2
Description
Actions
Title
SI Movie 1
Description
Actions
Title
SI Movie 2
Description
Actions
Title
SI Movie 3
Description
Actions
Title
SI Movie 4
Description
Actions
Title
SI Movie 5
Description
Actions
Title
SI combined final
Description
Actions

Comments

Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.

Now Published

A Chemical Probe for Dark Kinase STK17B Derives Its Potency and High Selectivity through a Unique P-Loop Conformation [opens in a new tab]
Alfredo Picado, Apirat Chaikuad, Carrow I. Wells, Safal Shrestha, William J. Zuercher, Julie E. Pickett, Frank E. Kwarcinski, Parvathi Sinha, Chandi S. de Silva, Reena Zutshi, Shubin Liu, Natarajan Kannan, Stefan Knapp, David H. Drewry, Timothy M. Willson journal article
Journal of Medicinal Chemistry , Volume 63, Issue 23
Online publication date: Nov 20, 2020

Version History

Jul 07, 2020 Version 1

Metrics

2,657
826
0
Views
Downloads
Citations

License

CC logo
CC
BY logo
BY
NC logo
NC
ND logo
ND
The content is available under CC BY NC ND 4.0 [opens in a new tab]

DOI

10.26434/chemrxiv.12616178.v1
D O I: 10.26434/chemrxiv.12616178.v1 [opens in a new tab]

Funding

1R44TR001916-02
1R01CA218442-01
1U24DK116204-01
1U01CA239106-01

Author’s competing interest statement

No conflict of interest

Share