SAHA (NSC 701852)

Overview

SAHA is a potent histone deactylase (HDAC) inhibitor with excellent oral bioavailability. Histone acetylation affects the regulation of gene expression and HDAC inhibitors may cause growth arrest, differentiation, and/or apoptosis of may transformed cells by altering the transcription of a small number of key genes. The HDAC inhibitors' activity in several animal models of solid tumors and leukemias, at doses that cause little apparent toxicity, suggest that these agents may be a new class of anticancer therapeutics.

Basic Chemistry

• Chemical Names: SAHA, suberoylanilide hydroxamic acid, vorinostat
• Chemical Structure: lipophilic hydroxamic acid

Preclinical Studies

• in vitro
  • biochemical assays
  • 60 cell screen:
    • Overall mean GI50 (5 experiments) is 920 nM. The most sensitive lines include RPMI-8226 myeloma line (200 nM) and NCI/ADR-RES ovarian line (100 nM). The least sensitive lines include HS578T breast line (8 µM) and OVCAR-4 ovarian line (5 µM).

      dose response | mean graph (GI50)

• in vivo
  • efficacy studies:

    Screening data summary reports for individual experiments using the DTP invivo solid tumor and/or toxicity testing models are available below. Comments are based upon the results of individual experiments. Variations in outcome can result from changes in many experimental variables including the drug doses, administration routes, dosing schedules, drug vehicles, tumor models and tumor passage status.

    toxicity, PSN-1 xenograft models

Clinical Studies

• IND
  • filed: March 18, 2005
  • activated: April 17, 2005
• CTEP Solicitation for Phase I and II Trial Letters of Intent Suberoylanilide Hydroxamic Acid
• active trials