7ZYW
Crystal structure of T2R-TTL-PM534 complex
Summary for 7ZYW
| Entry DOI | 10.2210/pdb7zyw/pdb |
| Descriptor | Tubulin alpha-1B chain, GUANOSINE-5'-DIPHOSPHATE, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, ... (15 entities in total) |
| Functional Keywords | tubulin, microtubule destabilizing agents, inhibitor, cell cycle/inhibitor, cell cycle-inhibitor complex |
| Biological source | Rattus norvegicus (Norway rat) More |
| Total number of polymer chains | 6 |
| Total formula weight | 271088.10 |
| Authors | Oliva, M.A.,Diaz, J.F.,Cuevas, C. (deposition date: 2022-05-25, release date: 2023-11-29, Last modification date: 2024-06-12) |
| Primary citation | Lucena-Agell, D.,Guillen, M.J.,Matesanz, R.,Alvarez-Bernad, B.,Hortiguela, R.,Aviles, P.,Martinez-Diez, M.,Santamaria-Nunez, G.,Contreras, J.,Plaza-Menacho, I.,Gimenez-Abian, J.F.,Oliva, M.A.,Cuevas, C.,Diaz, J.F. PM534, an Optimized Target-Protein Interaction Strategy through the Colchicine Site of Tubulin. J.Med.Chem., 67:2619-2630, 2024 Cited by PubMed Abstract: Targeting microtubules is the most effective wide-spectrum pharmacological strategy in antitumoral chemotherapy, and current research focuses on reducing main drawbacks: neurotoxicity and resistance. PM534 is a novel synthetic compound derived from the Structure-Activity-Relationship study on the natural molecule PM742, isolated from the sponge of the , family , genus (du Bocage 1869). PM534 targets the entire colchicine binding domain of tubulin, covering four of the five centers of the pharmacophore model. Its nanomolar affinity and high retention time modulate a strikingly high antitumor activity that efficiently overrides two resistance mechanisms in cells (detoxification pumps and tubulin βIII isotype overexpression). Furthermore, PM534 induces significant inhibition of tumor growth in mouse xenograft models of human non-small cell lung cancer. Our results present PM534, a highly effective new compound in the preclinical evaluation that is currently in its first human Phase I clinical trial. PubMed: 38294341DOI: 10.1021/acs.jmedchem.3c01775 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.45 Å) |
Structure validation
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