Summary for 9FU2
| Entry DOI | 10.2210/pdb9fu2/pdb |
| Descriptor | Myosin-11, ADENOSINE-5'-DIPHOSPHATE, VANADATE ION, ... (9 entities in total) |
| Functional Keywords | smooth muscle myosin ii;mt-228;myosin modulator;addiction;therapy;drug design, motor protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 229264.84 |
| Authors | Kikuti, C.M.,Houdusse, A. (deposition date: 2024-06-26, release date: 2025-07-09, Last modification date: 2025-09-03) |
| Primary citation | Radnai, L.,Young, E.J.,Kikuti, C.,Toth, K.,Zhou, M.,Hafenbreidel, M.,Stremel, R.F.,Lin, L.,Pasetto, P.,Jin, X.,Patel, A.,Conlon, M.,Briggs, S.B.,Heidsieck, L.,Sweeney, H.L.,Sellers, J.,Krieger-Burke, T.,Martin, W.H.,Sisco, J.,Young, S.,Pearson, P.,Rumbaugh, G.,Araldi, G.L.,Duddy, S.K.,Cameron, M.D.,Surman, M.,Houdusse, A.,Griffin, P.R.,Kamenecka, T.M.,Miller, C.A. Development of clinically viable non-muscle myosin II small molecule inhibitors. Cell, 188:4604-4621.e15, 2025 Cited by PubMed Abstract: Non-muscle myosin II (NMII), a molecular motor that regulates critical processes such as cytokinesis and neuronal plasticity, has substantial therapeutic potential. However, translating this potential to in vivo use has been hampered by a lack of selective tools. The most prototypical non-selective inhibitor inactivates both NMII and cardiac muscle myosin II (CMII), a key regulator of heart function. Using rational drug design, we developed a series of NMII inhibitors that markedly improve tolerability by selectively targeting NMII over CMII, including MT-228 and clinical candidate MT-110. MT-228 and MT-110 have excellent properties, including high brain penetration and efficacy in preclinical models of methamphetamine use disorder (MUD), which has no current FDA-approved therapies. The structure of MT-228 bound to myosin II provides insight into its selectivity for NMII over CMII. The broad therapeutic windows of these NMII inhibitors provide valuable tools for the scientific community and a promising clinical candidate for the treatment of MUD. PubMed: 40602401DOI: 10.1016/j.cell.2025.06.006 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.581 Å) |
Structure validation
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