5if4

Discovery of Potent Myeloid Cell Leukemia-1 (Mcl-1) inhibitors using Structure-Based Design

spinqualitylabelsall models 5if4, resolution 2.39Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5if4 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 6AK Related: 5iez Gene: MCL1, BCL2L3 (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [MCL1_HUMAN] Involved in the regulation of apoptosis versus cell survival, and in the maintenance of viability but not of proliferation. Mediates its effects by interactions with a number of other regulators of apoptosis. Isoform 1 inhibits apoptosis. Isoform 2 promotes apoptosis. Publication Abstract from PubMed Myeloid cell leukemia 1 (Mcl-1) is an antiapoptotic member of the Bcl-2 family of proteins that when overexpressed is associated with high tumor grade, poor survival, and resistance to chemotherapy. Mcl-1 is amplified in many human cancers, and knockdown of Mcl-1 using RNAi can lead to apoptosis. Thus, Mcl-1 is a promising cancer target. Here, we describe the discovery of picomolar Mcl-1 inhibitors that cause caspase activation, mitochondrial depolarization, and selective growth inhibition. These compounds represent valuable tools to study the role of Mcl-1 in cancer and serve as useful starting points for the discovery of clinically useful Mcl-1 inhibitors. PDB ID CODES: Comp. 2: 5IEZ; Comp. 5: 5IF4. Discovery and biological characterization of potent myeloid cell leukemia-1 inhibitors.,Lee T, Bian Z, Zhao B, Hogdal LJ, Sensintaffar JL, Goodwin CM, Belmar J, Shaw S, Tarr JC, Veerasamy N, Matulis SM, Koss B, Fischer MA, Arnold AL, Camper DV, Browning CF, Rossanese OW, Budhraja A, Opferman J, Boise LH, Savona MR, Letai A, Olejniczak ET, Fesik SW FEBS Lett. 2017 Jan;591(1):240-251. doi: 10.1002/1873-3468.12497. Epub 2016 Dec, 19. PMID:27878989 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also B-cell lymphoma proteins 3D structures

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