6JUU
Crystal structure of ZAK in complex with compound 6r
Summary for 6JUU
| Entry DOI | 10.2210/pdb6juu/pdb |
| Descriptor | Mitogen-activated protein kinase kinase kinase MLT, ~{N}-[2,4-bis(fluoranyl)-3-[4-(3-methoxy-1~{H}-pyrazolo[3,4-b]pyridin-5-yl)-1,2,3-triazol-1-yl]phenyl]naphthalene-1-sulfonamide (3 entities in total) |
| Functional Keywords | zak, inhibitor, structural protein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 35871.01 |
| Authors | Kong, L.L.,Yun, C.H. (deposition date: 2019-04-15, release date: 2020-04-22, Last modification date: 2023-11-22) |
| Primary citation | Yang, J.,Shibu, M.A.,Kong, L.,Luo, J.,BadrealamKhan, F.,Huang, Y.,Tu, Z.C.,Yun, C.H.,Huang, C.Y.,Ding, K.,Lu, X. Design, Synthesis, and Structure-Activity Relationships of 1,2,3-Triazole Benzenesulfonamides as New Selective Leucine-Zipper and Sterile-alpha Motif Kinase (ZAK) Inhibitors. J.Med.Chem., 63:2114-2130, 2020 Cited by PubMed Abstract: ZAK is a new promising target for discovery of drugs with activity against antihypertrophic cardiomyopathy (HCM). A series of 1,2,3-triazole benzenesulfonamides were designed and synthesized as selective ZAK inhibitors. One of these compounds, binds tightly to ZAK protein ( = 8.0 nM) and potently suppresses the kinase function of ZAK with single-digit nM (IC = 4.0 nM) and exhibits excellent selectivity in a KINOMEscan screening platform against a panel of 403 wild-type kinases. This compound dose dependently blocks p38/GATA-4 and JNK/c-Jun signaling and demonstrates promising in vivo anti-HCM efficacy upon oral administration in a spontaneous hypertensive rat (SHR) model. Compound may serve as a lead compound for new anti-HCM drug discovery. PubMed: 31244114DOI: 10.1021/acs.jmedchem.9b00664 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.903 Å) |
Structure validation
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