8i0c | pdb_00008i0c

Crystal structure of Aldo-keto reductase 1C3 complexed with compound S0703

spinqualitylabelsall models 8i0c, resolution 2.33Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8i0c is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.33Å Ligands: JTN, NAP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function AK1C3_HUMAN Catalyzes the conversion of aldehydes and ketones to alcohols. Catalyzes the reduction of prostaglandin (PG) D2, PGH2 and phenanthrenequinone (PQ) and the oxidation of 9-alpha,11-beta-PGF2 to PGD2. Functions as a bi-directional 3-alpha-, 17-beta- and 20-alpha HSD. Can interconvert active androgens, estrogens and progestins with their cognate inactive metabolites. Preferentially transforms androstenedione (4-dione) to testosterone. Publication Abstract from PubMed Aldo-keto reductase 1C3 (AKR1C3) is correlated with tumor development and chemotherapy resistance. The catalytic activity of the enzyme has been recognized as one of the important factors in inducing anthracycline (ANT) resistance in cancer cells. Inhibition of AKR1C3 activity may provide a promising approach to restore the chemosensitivity of ANT-resistant cancers. Herein, a series of biaryl-containing AKR1C3 inhibitors has been developed. The best analogue S07-1066 selectively blocked AKR1C3-mediated reduction of doxorubicin (DOX) in MCF-7 transfected cell models. Furthermore, co-treatment of S07-1066 significantly synergized DOX cytotoxicity and reversed the DOX resistance in MCF-7 cells overexpressing AKR1C3. The potential synergism of S07-1066 over DOX cytotoxicity was demonstrated in vitro and in vivo. Our findings indicate that inhibition of AKR1C3 potentially enhances the therapeutic efficacy of ANTs and even suggests that AKR1C3 inhibitors may serve as effective adjuvants to overcome AKR1C3-mediated chemotherapy resistance in cancer treatment. Development of Biaryl-Containing Aldo-Keto Reductase 1C3 (AKR1C3) Inhibitors for Reversing AKR1C3-Mediated Drug Resistance in Cancer Treatment.,He S, Chu X, Wu Y, Jiang J, Fang P, Chen Y, Liu Y, Qiu Z, Xiao Y, Li Z, Pan D, Zhang Q, Xie H, Xing S, Feng F, Liu W, Guo Q, Zhao L, Yang P, Sun H J Med Chem. 2023 Jul 27;66(14):9537-9560. doi: 10.1021/acs.jmedchem.3c00213. Epub , 2023 Jul 6. PMID:37409679 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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