SGC-CAMKK2-1: A Chemical Probe for CAMKK2

Carrow Wells; Yi Liang; Thomas L Pulliam; Chenchu Lin; Dominik Awad; Benjamin Eduful; Sean O'Byrne; Mohammad Anwar Hossain; Carolina Moura Costa Catta-Preta; Priscila Zonzini Ramos; Opher Gileadi; Carina Gileadi; Rafael M Couñago; Brittany Stork; Christopher G Langendorf; Kevin Nay; Jonathan S Oakhill; Debarati Mukherjee; Luigi Racioppi; Anthony R Means; Brian York; Donald P McDonnell; John W Scott; Daniel E Frigo; David H Drewry

doi:10.3390/cells12020287

SGC-CAMKK2-1: A Chemical Probe for CAMKK2

Cells. 2023 Jan 11;12(2):287. doi: 10.3390/cells12020287.

Authors

Carrow Wells¹, Yi Liang¹, Thomas L Pulliam², Chenchu Lin², Dominik Awad², Benjamin Eduful¹, Sean O'Byrne¹, Mohammad Anwar Hossain¹, Carolina Moura Costa Catta-Preta³, Priscila Zonzini Ramos³, Opher Gileadi³, Carina Gileadi³, Rafael M Couñago³, Brittany Stork⁴, Christopher G Langendorf⁵, Kevin Nay^{5

6}, Jonathan S Oakhill⁵, Debarati Mukherjee⁷, Luigi Racioppi^{8

9}, Anthony R Means⁴, Brian York⁴, Donald P McDonnell⁷, John W Scott^{5

6

10}, Daniel E Frigo^{2

11

12

13}, David H Drewry^{1

14}

Affiliations

¹ Structural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
² Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
³ Centro de Química Medicinal (CQMED), Centro de Biologia Molecular e Engenharia Genética (CBMEG), Universidade Estadual de Campinas (UNICAMP), Campinas 13083-886, Brazil.
⁴ Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
⁵ St Vincent's Institute of Medical Research, Fitzroy, VIC 3065, Australia.
⁶ Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Parkville, VIC 3052, Australia.
⁷ Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27705, USA.
⁸ Department of Medicine, Division of Hematological Malignancies and Cellular Therapy, Duke University School of Medicine, Durham, NC 27710, USA.
⁹ Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy.
¹⁰ The Florey Institute of Neuroscience and Mental Health, Parkville, VIC 3052, Australia.
¹¹ Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
¹² Center for Nuclear Receptors and Cell Signaling, University of Houston, Houston, TX 77204, USA.
¹³ Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA.
¹⁴ Lineberger Comprehensive Cancer Center, Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

Abstract

The serine/threonine protein kinase calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) plays critical roles in a range of biological processes. Despite its importance, only a handful of inhibitors of CAMKK2 have been disclosed. Having a selective small molecule tool to interrogate this kinase will help demonstrate that CAMKK2 inhibition can be therapeutically beneficial. Herein, we disclose SGC-CAMKK2-1, a selective chemical probe that targets CAMKK2.

Keywords: CAMKK2; NanoBRET; chemical probe; kinase; kinase selectivity.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Abstract

Publication types

Grants and funding