BIM (BCL2L11)
BIM is a pro-death protein that leukaemia cells keep clamped by BCL-2. Venetoclax and sonrotoclax are BH3 mimetics: they copy the part of BIM that binds BCL-2, so BIM is released, the mitochondria leak and the cell dies.
Overview
BCL2L11 (chromosome 2q13) encodes BIM, a BCL-2 family protein whose isoforms induce apoptosis and anoikis with differing potency: BimL is more potent than BimEL, the short Bim-alpha isoforms are weaker, and the BimAC and BimABC isoforms cannot induce apoptosis at all (UniProt O43521). The intrinsic apoptosis pathway record places BIM among the BH3-only proteins (with PUMA, NOXA and BAD) that either inhibit BCL-2, BCL-XL and MCL-1 or directly activate BAX and BAK. In OnCo the BH3 mimetics venetoclax and sonrotoclax occupy the BH3-binding groove of BCL-2 so that sequestered BIM and BAX are released, the mitochondrial outer membrane is permeabilised, cytochrome c triggers caspase activation and CLL, AML and mantle-cell lymphoma cells die within hours.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · BIM is a pro-death protein that leukaemia cells keep clamped by BCL-2. Venetoclax and sonrotoclax are BH3 mimetics: they copy the part of BIM that binds BCL-2, so BIM is released, the mitochondria leak and the cell dies.
- 1 · What it is
BIM is a pro-death protein that leukaemia cells keep clamped by BCL-2. Venetoclax and sonrotoclax are BH3 mimetics: they copy the part of BIM that binds BCL-2, so BIM is released, the mitochondria leak and the cell dies.
- 2 · What goes wrong in cancer
BIM itself is not a drug target; the drugs mimic its BH3 domain.
- 3 · How drugs use it
No product in this corpus aims at BIM (BCL2L11) yet. Drugs bind the molecule precisely: to switch it off, flag the cell for the immune system, or deliver a payload.
External identifiers
Biology
BIM itself is not a drug target; the drugs mimic its BH3 domain. Sonrotoclax is recorded as more potent and shorter-acting than venetoclax and active against the venetoclax-resistant G101V BCL2 mutation in preclinical models; both need a ramp-up for tumour lysis precautions.
- Chronic lymphocytic leukaemia and AML (venetoclax)
- Mantle-cell lymphoma and DLBCL (sonrotoclax)
Notes
top- Prevalence not recorded in this wave: HGNC and UniProt carry no positivity rates and no other source was consulted.
Latest papers
topQuery for this target: (TITLE:"BIM" OR ABSTRACT:"BIM" OR TITLE:"BCL2L11" OR ABSTRACT:"BCL2L11" OR TITLE:"BH3-only protein BIM" OR ABSTRACT:"BH3-only protein BIM" OR TITLE:"BH3" OR ABSTRACT:"BH3" OR TITLE:"BimEL" OR ABSTRACT:"BimEL" OR TITLE:"BimL" OR ABSTRACT:"BimL") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about BIM (BCL2L11), not a curated reading list.
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