Summary for 9HFP
| Entry DOI | 10.2210/pdb9hfp/pdb |
| Descriptor | Rho-associated protein kinase 2, ~{N}-[4-[(3~{R})-piperidin-3-yl]oxyphenyl]-1~{H}-pyrrolo[2,3-b]pyridin-4-amine (2 entities in total) |
| Functional Keywords | kinase, complex structure, inhibitor, transferase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 45780.10 |
| Authors | |
| Primary citation | Namoto, K.,Vangrevelinghe, E.,Machauer, R.,Behnke, D.,Buschmann, N.,Lachal, J.,Schipp, K.,Sorge, M.,Barker, K.,Fabbiani, F.,Piechon, P.,Connor, L.E.,Laurent, S.,Lohmann, F.,Unterreiner, V.,George, E.L.,Redmond, E.,Wang, L.,Scheufler, C.,Sohal, B.,Sailer, A.W.,Glatthar, R.,Tchorz, J.S.,Maibaum, J. Discovery and Optimization of Selective Inhibitors of Large Tumor Suppressor Kinases LATS1 and 2 for In Vivo Investigation of the Hippo-YAP Pathway in Tissue Regeneration. J.Med.Chem., 2025 Cited by PubMed Abstract: Large Tumor Suppressor kinases LATS1 and 2 (LATS1/2) are serine/threonine kinases and core regulators of the Hippo-YAP pathway. Inhibition of LATS1/2 promotes nuclear translocation of nonphosphorylated YAP, thereby initiating a downstream cascade promoting cell proliferation. We set out to investigate the potential of LATS inhibition as a therapeutic approach to enhance tissue regeneration and hereby report a structure-guided optimization of screening hit for potency, binding efficiency, and physicochemical properties, leading to a highly selective, cellularly active, and orally available tool compound (NIBR-LTSi) that demonstrated target engagement and in vivo YAP target gene activation in rodents. PubMed: 40574495DOI: 10.1021/acs.jmedchem.5c00350 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.92 Å) |
Structure validation
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