7zyw

Crystal structure of T2R-TTL-PM534 complex

spinqualitylabelsall models 7zyw, resolution 2.45Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7zyw is a 6 chain structure with sequence from Bos taurus, Gallus gallus and Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.45Å Ligands: ACP, CA, CL, DMS, GDP, GOL, GTP, KG0, MES, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 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 order Lithistida, family Theonellidae, genus Discodermia (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 betaIII 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. PM534, an Optimized Target-Protein Interaction Strategy through the Colchicine Site of Tubulin.,Lucena-Agell D, Guillen MJ, Matesanz R, Alvarez-Bernad B, Hortiguela R, Aviles P, Martinez-Diez M, Santamaria-Nunez G, Contreras J, Plaza-Menacho I, Gimenez-Abian JF, Oliva MA, Cuevas C, Diaz JF J Med Chem. 2024 Feb 22;67(4):2619-2630. doi: 10.1021/acs.jmedchem.3c01775. Epub , 2024 Jan 31. PMID:38294341 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Stathmin-4 3D structures Tubulin 3D Structures Tubulin tyrosine ligase 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA