5USQ

ALK-5 kinase inhibitor complex

Summary for 5USQ

• Entry DOI: 10.2210/pdb5usq/pdb
• Descriptor: TGF-beta receptor type-1, N-[2-(5-chloro-2-fluorophenyl)pyridin-4-yl]-2-[(piperidin-4-yl)methyl]-2H-pyrazolo[4,3-b]pyridin-7-amine (3 entities in total)
• Functional Keywords: tgf-beta receptor type i, serine/threonine-protein kinase receptor r4, activin receptor-like kinase 5, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (Human)
• Cellular location: Cell membrane ; Single-pass type I membrane protein : P36897
• Total number of polymer chains: 1
• Total formula weight: 34702.31

Authors

Dougan, D.R.,Lawson, J.D. (deposition date: 2017-02-13, release date: 2017-04-12, Last modification date: 2024-03-06)

Primary citation

Sabat, M.,Wang, H.,Scorah, N.,Lawson, J.D.,Atienza, J.,Kamran, R.,Hixon, M.S.,Dougan, D.R.
Design, synthesis and optimization of 7-substituted-pyrazolo[4,3-b]pyridine ALK5 (activin receptor-like kinase 5) inhibitors.
Bioorg. Med. Chem. Lett., 27:1955-1961, 2017

PubMed Abstract: A series of potent ALK5 inhibitors were designed using a SBDD approach and subsequently optimized to improve drug likeness. Starting with a 4-substituted quinoline screening hit, SAR was conducted using a ALK5 binding model to understand the binding site and optimize activity. The resulting inhibitors displayed excellent potency but were limited by high in vitro clearance in rat and human microsomes. Using a scaffold morphing strategy, these analogs were transformed into a related pyrazolo[4,3-b]pyridine series with improved ADME properties.

PubMed: 28359790
DOI: 10.1016/j.bmcl.2017.03.026

Experimental method

X-RAY DIFFRACTION (2.55 Å)