9BHK

MerTK in complex with small molecule inhibitor 6-{1-[6-(3-hydroxy-3-methylbutoxy)-1,3-benzoxazol-2-yl]azetidin-3-yl}-3-[(1-methyl-1H-pyrazol-4-yl)amino]pyrazine-2-carboxamide

This is a non-PDB format compatible entry.

Summary for 9BHK

• Entry DOI: 10.2210/pdb9bhk/pdb
• Descriptor: Tyrosine-protein kinase Mer, 6-{1-[6-(3-hydroxy-3-methylbutoxy)-1,3-benzoxazol-2-yl]azetidin-3-yl}-3-[(1-methyl-1H-pyrazol-4-yl)amino]pyrazine-2-carboxamide, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: transferase kinase atp competitive inhibitor, transferase-inhibitor complex, transferase/inhibitor
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 38041.36

Authors

Jakob, C.G.,Gurbani, D.,Qiu, W. (deposition date: 2024-04-20, release date: 2024-10-09, Last modification date: 2024-10-23)

Primary citation

Frey, R.R.,Jana, N.,Gorman, J.V.,Wang, J.,Smith, H.A.,Bromberg, K.D.,Thakur, A.,Doktor, S.Z.,Indulkar, A.S.,Jakob, C.G.,Upadhyay, A.K.,Qiu, W.,Manaves, V.,Gambino Jr., F.,Valentino, S.A.,Montgomery, D.,Zhou, Y.,Li, T.,Buchanan, F.G.,Ferguson, D.C.,Kurnick, M.D.,Kapecki, N.,Lai, A.,Michaelides, M.R.,Penning, T.D.
Discovery of Potent Azetidine-Benzoxazole MerTK Inhibitors with In Vivo Target Engagement.
J.Med.Chem., 67:17033-17052, 2024

PubMed Abstract: Inhibition of the receptor tyrosine kinase MerTK by small molecules has the potential to augment the immune response to tumors. Potent, selective inhibitors with high levels of target engagement are needed to fully evaluate the potential use of MerTK inhibitors as cancer therapeutics. We report the discovery and optimization of a series of pyrazinamide-based type 1.5 MerTK inhibitors bearing an azetidine-benzoxazole substituent. Compound potently engages the target and demonstrates single agent activity in the immune-driven MC-38 murine syngeneic tumor model.

PubMed: 39350472
DOI: 10.1021/acs.jmedchem.4c01451

Experimental method

X-RAY DIFFRACTION (2.106 Å)