Citarinostat (ACY-241)

Citarinostat (ACY-241) is a potential oral treatment that selectively inhibits (blocks) histone deacetylase 6 (HDAC6). It is currently being investigated as a potential treatment to stop the growth of certain types of cancer, including myeloma, melanoma, and non-small cell lung cancer.

In contrast to non-selective HDAC inhibitors that block more than one HDAC, citarinostat exhibits selective activity against HDAC6 only. For this reason, citarinostat is thought to be a safer treatment, with fewer side effects.

Citarinostat was originally developed by Acetylon Pharmaceuticals, which was later acquired by Celgene. Celgene is now part of Bristol Myers Squibb.

How does citarinostat work?

Citarinostat works to block the proliferation of cancer cells by inhibiting an enzyme, HDAC6, that is needed for cell growth. HDAC6 is responsible for removing acetyl groups from histone proteins.

HDACs are present at high levels in many types of tumor, and help in the proliferation and growth of cancer cells. The inhibition of HDAC6 by citarinostat means that the enzyme is unable to remove acetyl groups from histone proteins. This results in the accumulation of highly acetylated histones, which leads to an alteration in the structure of chromatin and the inhibition of gene expression associated with cancer cell division, resulting in the death of tumor cells.

Preclinical studies in multiple solid tumor cell lines showed that treatment with a combination of citarinostat and paclitaxel worked to lower cell proliferation, increase cell death, and suppress solid tumor growth better than either treatment alone.

Citarinostat in clinical trials

A multicenter, open-label, dose-escalation Phase 1a/1b clinical trial (NCT02400242) called ACE-MM-200, is evaluating the safety and preliminary anti-tumor activity of citarinostat alone and in combination with Pomalyst (pomalidomide) and dexamethasone in 85 patients with relapsed or relapsed and refractory multiple myeloma (RRMM). The study is being conducted at sites in France, Germany, Greece, Spain, and the U.S., and is expected to be completed in June 2020.

Initial study results showed that citarinostat is well-tolerated alone and in combination with Pomalyst and dexamethasone. The combination treatment also showed promising anti-tumor activity, with patients living longer without cancer progression.

An open-label, multicenter, and dose-escalation Phase 1b study (NCT02551185) evaluated the safety, pharmacokinetics (movement in the body), and preliminary anti-tumor activity of citarinostat in combination with paclitaxel in 20 patients with advanced solid tumors, including those who failed to respond to previous treatment.

Study results showed the combination of citarinostat and paclitaxel to be safe in heavily pre-treated patients and without unexpected side effects.

Another open-label Phase 1 study (NCT02886065) is enrolling up to 20 patients with smoldering multiple myeloma in the U.S. to evaluate the efficacy of citarinostat in combination with PVX-410 (a multi-peptide cancer vaccine), and  in combination with both PVX-410 and Revlimid (lenalidomide). This trial, which still may be recruiting at its four sites, is expected to conclude in May 2021.


Last updated: Feb. 21, 2020


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