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all-trans retinoic acid + bryostatin 1
- Development stage
- Discontinued
- Lead developer
- Dana-Farber Cancer Institute
- Modality
- Small Molecules
- Administration
- Oral, Intravenous
01
Overview
This combination therapy consists of all-trans retinoic acid (ATRA), a vitamin A derivative, and bryostatin 1, a macrocyclic lactone derived from the marine bryozoan *Bugula neritina*. ATRA acts as a differentiating agent by binding to nuclear retinoic acid receptors (RARs), specifically RAR-alpha, RAR-beta, and RAR-gamma, which function as transcription factors to regulate gene expression related to myeloid cell maturation. Bryostatin 1 is a potent modulator of protein kinase C (PKC), an enzyme involved in various signal transduction pathways. The combination was investigated by the Dana-Farber Cancer Institute in Phase II clinical trials for patients with refractory acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). The therapeutic rationale is based on the synergy between PKC activation and retinoid signaling to overcome the differentiation block characteristic of non-promyelocytic AML and high-risk MDS cells.
- Other names
- ATRA + bryostatin 1tretinoin + bryostatin 1all-trans retinoic acid + bryostatin-1
02
Targets
RARA (Retinoic acid receptor alpha)RARB (Retinoic acid receptor beta)RARG (Retinoic acid receptor gamma)PKC (Protein kinase C family)
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