IKZF3 (Aiolos)
Aiolos is Ikaros' partner transcription factor in B cells and plasma cells. The myeloma drugs lenalidomide, pomalidomide and golcadomide destroy Aiolos and Ikaros together by rerouting them to the cell's protein-disposal system.
Overview
IKZF3 (chromosome 17q12-q21.1) encodes Aiolos, a transcription factor that regulates lymphocyte differentiation and is essential for B-cell differentiation, proliferation and maturation to an effector state; it regulates BCL2 expression and controls IL-2-dependent apoptosis in T cells (UniProt Q9UKT9). In OnCo it is the second cereblon neosubstrate, alongside Ikaros, that lenalidomide and pomalidomide recruit for ubiquitination and proteasomal degradation and that golcadomide degrades; the loss lowers IRF4 and MYC in myeloma cells and stimulates T and NK cells.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · Aiolos is Ikaros' partner transcription factor in B cells and plasma cells. The myeloma drugs lenalidomide, pomalidomide and golcadomide destroy Aiolos and Ikaros together by rerouting them to the cell's protein-disposal system.
- 1 · What it is
Aiolos is Ikaros' partner transcription factor in B cells and plasma cells. The myeloma drugs lenalidomide, pomalidomide and golcadomide destroy Aiolos and Ikaros together by rerouting them to the cell's protein-disposal system.
- 2 · What goes wrong in cancer
Aiolos and Ikaros are destroyed by the same molecular-glue mechanism: the drug binds cereblon in the CRL4 ligase, the complex gains affinity for both transcription factors, and both are ubiquitinated (lenalidomide mechanism steps).
- 3 · How drugs use it
3 products aim at IKZF3 (Aiolos): degraders. Transcription factors have no pocket to plug, so drugs either degrade them or block the partner protein they need to dock on DNA.
External identifiers
Biology
Aiolos and Ikaros are destroyed by the same molecular-glue mechanism: the drug binds cereblon in the CRL4 ligase, the complex gains affinity for both transcription factors, and both are ubiquitinated (lenalidomide mechanism steps). Pomalidomide keeps this activity after lenalidomide failure.
- Multiple myeloma (degradation by immunomodulatory drugs and CELMoDs)
- Diffuse large B-cell lymphoma (golcadomide trials)
Golcadomide is a next-generation lenalidomide-like pill that degrades two lymphoma transcription factors far more potently, now in phase 3 with R-CHOP.
Lenalidomide is a thalidomide descendant that glues the proteins IKZF1 and IKZF3 to cereblon so the cell destroys them, killing plasma cells and rousing T cells. It is the backbone of myeloma treatment and maintenance, also used in mantle cell and follicular lymphoma, and generic since 2022.
The third-generation thalidomide analogue for myeloma that has failed lenalidomide, and since 2020 the first new drug for Kaposi sarcoma in two decades.
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:"IKZF3" OR ABSTRACT:"IKZF3" OR TITLE:"Aiolos" OR ABSTRACT:"Aiolos" OR TITLE:"ZNFN1A3" OR ABSTRACT:"ZNFN1A3" OR TITLE:"IKAROS family zinc finger 3" OR ABSTRACT:"IKAROS family zinc finger 3") 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 IKZF3 (Aiolos), not a curated reading list.
Similar pages
not linked directly; found by shared links- TargetBAX
Shares BCL-2, Diffuse large B-cell lymphoma and the tag wave5-target.
- TargetBIM (BCL2L11)
Shares BCL-2, Diffuse large B-cell lymphoma and the tag wave5-target.
- TargetBRD4
Shares Transcriptional machinery & addiction and the tag wave5-target.
- TargetCD28
Shares Diffuse large B-cell lymphoma and the tag wave5-target.
- TreatmentIberdomide
Shares Cereblon E3 ligase modulators (CELMoDs), Ubiquitin-proteasome system & protein homeostasis, Lenalidomide, Relapsed or refractory multiple myeloma.
- TermImmunomodulatory drugs (IMiDs) and CELMoDs
Shares Molecular glue discovery platforms, Pomalidomide, Lenalidomide, Relapsed or refractory multiple myeloma.
- TrialA Study to Evaluate Mezigdomide, Bortezomib and Dexamethasone (MEZIVd) Versus Pomalidomide, Bortezomib and Dexamethasone (PVd) in Participants With Re
Shares Cereblon E3 ligase modulators (CELMoDs), Pomalidomide, Relapsed or refractory multiple myeloma, Multiple myeloma.
- TreatmentMezigdomide
Shares Cereblon E3 ligase modulators (CELMoDs), Ubiquitin-proteasome system & protein homeostasis, Relapsed or refractory multiple myeloma, Multiple myeloma.