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

A Chemical Probe Targeting AAK1 and BMP2K

04 September 2019, Version 1

Abstract

Inhibitors based on a 3-acylaminoindazole scaffold were synthesized to yield potent dual AAK1/BMP2K inhibitors. Optimization of this 3-acylaminoindazole scaffold furnished a small molecule chemical probe (SGC-AAK1-1, 25) that is potent and selective for AAK1/BMP2K over other NAK family members, demonstrates narrow activity in a kinome-wide screen, and is functionally active in cells. This inhibitor represents one of the best available small molecule tools to study the functions of AAK1 and BMP2K.

Keywords

AAK1
BMP2K
NAK Family
Endocytosis
Protein kinase
acylaminoindazole

Supplementary materials

Title
Description
Actions
Title
ACS MCL experimental 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

SGC-AAK1-1: A Chemical Probe Targeting AAK1 and BMP2K [opens in a new tab]
Carrow Wells, Rafael M. Couñago, Juanita C. Limas, Tuanny L. Almeida, Jeanette Gowen Cook, David H. Drewry, Jonathan M. Elkins, Opher Gileadi, Nirav R. Kapadia, Alvaro Lorente-Macias, Julie E. Pickett, Alexander Riemen, Roberta R. Ruela-de-Sousa, Timothy M. Willson, Cunyu Zhang, William J. Zuercher, Reena Zutshi, Alison D. Axtman journal article
ACS Medicinal Chemistry Letters , Volume 11, Issue 3
Online publication date: Oct 23, 2019

Version History

Sep 04, 2019 Version 1

Metrics

3,216
646
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.9756785.v1
D O I: 10.26434/chemrxiv.9756785.v1 [opens in a new tab]

Funding

The Structural Genomics Consortium is a registered charity (number 1097737) that receives funds from AbbVie, Bayer Pharma AG, Boehringer Ingelheim, Canada Foundation for Innovation, Eshelman Institute for Innovation, Genome Canada, Janssen, Merck KGaA Darmstadt Germany, MSD, Novartis Pharma AG, Ontario Ministry of Economic Development and Innovation, Pfizer, São Paulo Research Foundation, Takeda, and Wellcome [106169/ZZ14/Z].
FAPESP/50724-5/2013
National Center for Advancing Translational Sciences
R44TR001916
Tools for Accelerating R&D for Historically Understudied Protein Kinases
https://app.dimensions.ai/details/grant/grant.6617154 [opens in a new tab]
Government of Spain-Ministry of Education, Culture and Sports/College of Spain - Training programme for Academic Staff (FPU grant ref. 14/00818)
National Institute of Allergy and Infectious Diseases
UM2AI130836
NEW HORIZONS IN THE PREVENTION AND TREATMENT OF FOOD ALLERGY
https://app.dimensions.ai/details/grant/grant.6617382 [opens in a new tab]
NC Biotech Center Institutional Support Grants 2017-IDG-1025 and 2018-IDG-1030
CNPq 465651/2014-3
Innovative Medicines Initiative ULTRA-DD grant no. 115766
National Institute of General Medical Sciences
R25GM089569
UNC PREP in the Biomedical Sciences
https://app.dimensions.ai/details/grant/grant.2623406 [opens in a new tab]
National Institute of General Medical Sciences
T32GM007040
Predoctoral Training in Pharmacological Sciences
https://app.dimensions.ai/details/grant/grant.2683656 [opens in a new tab]
National Cancer Institute
P30CA016086
Cancer Center Support Grant
https://app.dimensions.ai/details/grant/grant.2438821 [opens in a new tab]
HHMI Gilliam Fellowship for Advanced Study (GT10886)
National Institute of General Medical Sciences
R01GM083024
Replication Licensing and the Cell Cycle
https://app.dimensions.ai/details/grant/grant.2519811 [opens in a new tab]
FAPESP/5087-0/2014
FAPESP/17469-0/2016

Author’s competing interest statement

The authors declare no conflict of interest.

Share