Chemistry:Ricolinostat
Ricolinostat (INN, USAN; developmental code names ACY-1215 and ACY-63) is a histone deacetylase (HDAC) inhibitor which is under development for the treatment of diabetic neuropathies, multiple myeloma, and lymphoma.[1] It is taken orally.[1]
Pharmacology
| Enzyme | IC50 (nM) |
|---|---|
| HDAC1 | 58 |
| HDAC2 | 48 |
| HDAC3 | 51 |
| HDAC4 | 7,000 |
| HDAC5 | 5,000 |
| HDAC6 | 4.7 |
| HDAC7 | 1,400 |
| HDAC8 | 100 |
| HDAC9 | >10,000 |
| HDAC10 | ND |
| HDAC11 | >10,000 |
| Refs: [2] | |
Ricolinostat has been reported to have 10- to 21-fold selectivity for HDAC6 over HDAC1, HDAC2, HDAC3, and HDAC8 and greater than 1,000-fold selectivity for HDAC6 over other HDACs.[2] It has been referred to as the first selective HDAC6 inhibitor[3] and as a first-in-class selective HDAC6 inhibitor.[4] However, although described as a highly selective HDAC6 inhibitor, the drug's selectivity for HDAC6 appears to be controversial.[5][6] Ricolinostat has been found to improve cognition and memory in rodent models of Alzheimer's disease.[7][8] It has also been found to reverse cognitive impairment induced by cisplatin, also known as chemotherapy cognitive impairment, in rodents.[9][10] The pharmacokinetics of ricolinostat have been studied in rodents.[2]
Side effects
Side effects of ricolinostat have been reported to include diarrhea, nausea, fatigue, anemia, and hypercalcemia, among others.[4]
History
Ricolinostat was first described in the scientific literature by 2012.[2] It has been developed by Dana-Farber Cancer Institute, Harvard University, 3E-Regenacy Pharmaceuticals (BC Regenacy), Columbia University, and Regenacy Pharmaceuticals.[1] As of February 2025, the drug is in phase 2 clinical trials for diabetic neuropathies and multiple myeloma and is in phase 1/2 trials for lymphoma.[1] It is or was also under development for a variety of other uses, including breast cancer, Charcot-Marie-Tooth disease, chronic lymphocytic leukemia, fallopian tube cancer, malignant melanoma, ovarian cancer, peripheral nervous system diseases, and peritoneal cancer, but no recent development has been reported for these indications.[1]
See also
References
- ↑ 1.0 1.1 1.2 1.3 1.4 "Regenacy Pharmaceuticals". 28 February 2025. https://adisinsight.springer.com/drugs/800032606.
- ↑ 2.0 2.1 2.2 2.3 "Preclinical activity, pharmacodynamic, and pharmacokinetic properties of a selective HDAC6 inhibitor, ACY-1215, in combination with bortezomib in multiple myeloma". Blood 119 (11): 2579–2589. March 2012. doi:10.1182/blood-2011-10-387365. PMID 22262760.
- ↑ "Ricolinostat, the First Selective Histone Deacetylase 6 Inhibitor, in Combination with Bortezomib and Dexamethasone for Relapsed or Refractory Multiple Myeloma". Clinical Cancer Research 23 (13): 3307–3315. July 2017. doi:10.1158/1078-0432.CCR-16-2526. PMID 28053023.
- ↑ 4.0 4.1 "First-in-Class Selective HDAC6 Inhibitor (ACY-1215) Has a Highly Favorable Safety Profile in Patients with Relapsed and Refractory Lymphoma". The Oncologist 26 (3): 184–e366. March 2021. doi:10.1002/onco.13673. PMID 33458921.
- ↑ "Ricolinostat is not a highly selective HDAC6 inhibitor". Nature Cancer 4 (6): 807–808. June 2023. doi:10.1038/s43018-023-00582-3. PMID 37322365.
- ↑ "Reply to: Ricolinostat is not a highly selective HDAC6 inhibitor". Nature Cancer 4 (6): 809–811. June 2023. doi:10.1038/s43018-023-00583-2. PMID 37322366.
- ↑ "Tubastatin A/ACY-1215 improves cognition in Alzheimer's disease transgenic mice". Journal of Alzheimer's Disease 41 (4): 1193–1205. 2014. doi:10.3233/JAD-140066. PMID 24844691.
- ↑ "Melatonin- and Ferulic Acid-Based HDAC6 Selective Inhibitors Exhibit Pronounced Immunomodulatory Effects In Vitro and Neuroprotective Effects in a Pharmacological Alzheimer's Disease Mouse Model". Journal of Medicinal Chemistry 64 (7): 3794–3812. April 2021. doi:10.1021/acs.jmedchem.0c01940. PMID 33769811.
- ↑ "Pharmacological inhibition of HDAC6 reverses cognitive impairment and tau pathology as a result of cisplatin treatment". Acta Neuropathologica Communications 6 (1). October 2018. doi:10.1186/s40478-018-0604-3. PMID 30270813.
- ↑ "Protective Effects of ACY-1215 Against Chemotherapy-Related Cognitive Impairment and Brain Damage in Mice". Neurochemical Research 44 (11): 2460–2469. November 2019. doi:10.1007/s11064-019-02882-6. PMID 31571096.
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