7NCF

Crystal structure of HIPK2 in complex with MU135 (compound 21e)

Summary for 7NCF

• Entry DOI: 10.2210/pdb7ncf/pdb
• Descriptor: Homeodomain-interacting protein kinase 2, 3-(4-Tert-butylphenyl)-5-(1H-pyrazol-4-yl)furo[3,2-b]pyridine (3 entities in total)
• Functional Keywords: kinase, hipk2, kinase inhibitor, structural genomics, structural genomics consortium, sgc, transferase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 42763.90

Authors

Chaikuad, A.,Paruch, K.,Knapp, S.,Structural Genomics Consortium (SGC) (deposition date: 2021-01-28, release date: 2021-03-03, Last modification date: 2024-11-13)

Primary citation

Nemec, V.,Maier, L.,Berger, B.T.,Chaikuad, A.,Drapela, S.,Soucek, K.,Knapp, S.,Paruch, K.
Highly selective inhibitors of protein kinases CLK and HIPK with the furo[3,2-b]pyridine core.
Eur.J.Med.Chem., 215:113299-113299, 2021

PubMed Abstract: The furo [3,2-b]pyridine motif represents a relatively underexplored central pharmacophore in the area of kinase inhibitors. Herein, we report flexible synthesis of 3,5-disubstituted furo [3,2-b]pyridines that relies on chemoselective couplings of newly prepared 5-chloro-3-iodofuro [3,2-b]pyridine. This methodology allowed efficient second-generation synthesis of the state-of-the-art chemical biology probe for CLK1/2/4 MU1210, and identification of the highly selective inhibitors of HIPKs MU135 and MU1787 which are presented and characterized in this study, including the X-ray crystal structure of MU135 in HIPK2. chemical biology probe.

PubMed: 33636538
DOI: 10.1016/j.ejmech.2021.113299

Experimental method

X-RAY DIFFRACTION (2.72 Å)