Description

Commercial Opportunity
Novel compounds with HDAC-3 inhibitory activity have been rationally designed under funding from Cancer Research UK. HDAC-3 activity has been shown to be tightly linked to N-CoR/SMRT repressor complexes. Therefore these inhibitors are expected to have therapeutic activity in N-CoR/SMRTmediated cancers like Acute Myeloid leukaemia (AML). CRT is now seeking a co-development (or licensing) partner for the further development of these novel inhibitors. Data available under confidentiality includes biochemical IC50, compound physicochemical properties, in vitro ADME profiles, in vivo PK,
phenotypic efficacy studies and in vitro PD biomarker activity.

Background and Rationale
HDAC inhibitors (HDI) are effective inducers of apoptosis, cell cycle arrest and/or differentiation in malignant cells, with selectivity versus normal cells. Most available HDIs are pan inhibitors with poor isoform selectivity and high toxicity. The field currently needs HDI that will target specific enzymes known to play a central role in specific diseases leading to improved efficacy and tolerability.
HDAC-3 activity has been shown to be tightly linked to N-CoR/SMRT repressor complexes (1). HDAC-3 selective inhibitors are therefore expected to have therapeutic activity in N-CoR/SMRTmediated
cancers e.g. AML, Diff use B-cell Lymphoma (DBCL) and some types of breast and endometrial cancers. Moreover, siRNA-mediated knock-down of HDAC-3 has been shown to be suffi cient to decrease proliferation, survival and/or migration in ovarian, colon, cervical and synovial carcinoma cell lines (2-4). Thus, selective inhibition of HDAC-3 is likely to be an eff ective strategy for the treatment of various cancer types.

Download the PDF of Selective HDAC-2/3 inhibitors

For more information please contact

Dr Hanane Gouizi

+44 (0) 20 3469 6300 .(JavaScript must be enabled to view this email address)