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vorinostat + temozolomide
- Development stage
- Phase 2
- Lead developer
- Merck
- Modality
- Small Molecules
- Administration
- Oral
01
Overview
Vorinostat + temozolomide is a combination therapy consisting of the histone deacetylase (HDAC) inhibitor vorinostat and the DNA alkylating agent temozolomide. This combination was evaluated in a Phase 2 clinical trial (NCT01550224) led by Steven E. Coutre at Stanford University for the treatment of patients with relapsed or refractory acute myeloid leukemia (AML). Vorinostat, also known as suberoylanilide hydroxamic acid (SAHA), works by inhibiting Class I and II HDAC enzymes, which leads to the hyperacetylation of histones and subsequent induction of cell cycle arrest and apoptosis. Temozolomide is an oral alkylating agent that induces DNA damage. The combination strategy aims to exploit potential epigenetic sensitization of leukemia cells to alkylating agents, with the trial stratifying patients based on MGMT promoter methylation status.
- Other names
- suberoylanilide hydroxamic acid
02
Targets
HDAC1 (Histone Deacetylase 1)HDAC2 (Histone deacetylase 2)HDAC3 (Histone Deacetylase 3)HDAC6 (Histone deacetylase 6)DNA
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