9INP

Human Pin1 (Peptidyl-prolyl cis-trans isomerase) catalytic domain in complex with a covalent inhibitor

This is a non-PDB format compatible entry.

Summary for 9INP

• Entry DOI: 10.2210/pdb9inp/pdb
• Descriptor: Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1, ~{N}-[(3~{R})-1,1-bis(oxidanylidene)thiolan-3-yl]-2-chloranyl-~{N}-(2,2-dimethylpropyl)-5-nitro-pyrimidin-4-amine, CITRIC ACID, ... (4 entities in total)
• Functional Keywords: peptidyl-prolyl cis-trans isomerase, pin1, covalent inhibitor, isomerase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 27723.57

Authors

Wang, X.Y.,Tian, M.Z.,Zhou, J.,Xu, B.L. (deposition date: 2024-07-08, release date: 2025-05-14)

Primary citation

Tian, M.,Wang, X.,Tang, G.,Cui, G.,Zhou, J.,Jin, J.,Xu, B.
Discovery of Novel Pyrimidine Derivatives as Human Pin1 Covalent Inhibitors.
Acs Med.Chem.Lett., 16:101-108, 2025

PubMed Abstract: Pin1 (peptidyl-prolyl cis-trans isomerase NIMA-interacting 1) is a unique peptidyl-prolyl isomerase (PPIase), and inactivation of Pin1 with a covalent inhibitor is a potential strategy for developing anticancer agents. Herein, a series of sulfolane amino-substituted 2-chloro-5-nitropyrimidine derivatives were disclosed as structurally distinct covalent inhibitors toward Pin1, which were validated for their covalent binding to Cys113 of Pin1 by X-ray cocrystal structures of compounds (IC = 11.55 μM) and (IC = 3.15 μM). This work provided a new approach for covalent inhibition of Pin1 by taking advantage of the 2-chloro-5-nitropyrimidine as the electrophilic warhead, which might benefit the discovery of potent and drug-like Pin1 inhibitors.

PubMed: 39811131
DOI: 10.1021/acsmedchemlett.4c00477

Experimental method

X-RAY DIFFRACTION (2.57 Å)