|2w3l, resolution 2.10Å ()|
|Related:|| 1ysw, 1g5m, 1gjh
CRYSTAL STRUCTURE OF CHIMAERIC BCL2-XL AND PHENYL TETRAHYDROISOQUINOLINE AMIDE COMPLEX
Anti-apoptotic Bcl-2 protects cells from apoptosis by binding to pro-apoptotic members of the Bcl-2 family thereby playing a role in tumour survival in response to chemo- or radiation therapy. We describe a series of phenyl pyrazoles that have high affinity for Bcl-2 and rationalise the observed SAR by means of an X-ray crystal structure.
Tetrahydroisoquinoline amide substituted phenyl pyrazoles as selective Bcl-2 inhibitors., Porter J, Payne A, de Candole B, Ford D, Hutchinson B, Trevitt G, Turner J, Edwards C, Watkins C, Whitcombe I, Davis J, Stubberfield C, Bioorg Med Chem Lett. 2008 Oct 31. PMID:19027294
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
[BCL2_HUMAN] Note=A chromosomal aberration involving BCL2 has been found in chronic lymphatic leukemia. Translocation t(14;18)(q32;q21) with immunoglobulin gene regions. BCL2 mutations found in non-Hodgkin lymphomas carrying the chromosomal translocation could be attributed to the Ig somatic hypermutation mechanism resulting in nucleotide transitions.
[BCL2_HUMAN] Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1).
About this Structure
- Porter J, Payne A, de Candole B, Ford D, Hutchinson B, Trevitt G, Turner J, Edwards C, Watkins C, Whitcombe I, Davis J, Stubberfield C. Tetrahydroisoquinoline amide substituted phenyl pyrazoles as selective Bcl-2 inhibitors. Bioorg Med Chem Lett. 2008 Oct 31. PMID:19027294 doi:S0960-894X(08)01331-0