Ricolinostat
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| Other names | Rocilinostat; ACY-1215; ACY1215; ACY-63; ACY63 |
| Routes of administration | Oral[1] |
| Drug class | Histone deacetylase inhibitor; HDAC6 inhibitor |
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| Chemical and physical data | |
| Formula | C24H27N5O3 |
| Molar mass | 433.512 g·mol−1 |
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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
[edit]| 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] | |
The drug 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
[edit]Side effects of ricolinostat have been reported to include diarrhea, nausea, fatigue, anemia, and hypercalcemia, among others.[4]
History
[edit]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
[edit]References
[edit]- 1 2 3 4 5 6 "Regenacy Pharmaceuticals". AdisInsight. 28 February 2025. Retrieved 3 August 2026.
- 1 2 3 4 Santo L, Hideshima T, Kung AL, Tseng JC, Tamang D, Yang M, et al. (March 2012). "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. doi:10.1182/blood-2011-10-387365. PMC 3337713. PMID 22262760.
- ↑ Vogl DT, Raje N, Jagannath S, Richardson P, Hari P, Orlowski R, et al. (July 2017). "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. doi:10.1158/1078-0432.CCR-16-2526. PMC 5496796. PMID 28053023.
- 1 2 Amengual JE, Lue JK, Ma H, Lichtenstein R, Shah B, Cremers S, et al. (March 2021). "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. doi:10.1002/onco.13673. PMC 7930426. PMID 33458921.
- ↑ Médard G, Sheltzer JM (June 2023). "Ricolinostat is not a highly selective HDAC6 inhibitor". Nature Cancer. 4 (6): 807–808. doi:10.1038/s43018-023-00582-3. PMID 37322365.
- ↑ Silva J, Yu J, Kalinsky K (June 2023). "Reply to: Ricolinostat is not a highly selective HDAC6 inhibitor". Nature Cancer. 4 (6): 809–811. doi:10.1038/s43018-023-00583-2. PMID 37322366.
- ↑ Zhang L, Liu C, Wu J, Tao JJ, Sui XL, Yao ZG, et al. (2014). "Tubastatin A/ACY-1215 improves cognition in Alzheimer's disease transgenic mice". Journal of Alzheimer's Disease. 41 (4): 1193–1205. doi:10.3233/JAD-140066. PMID 24844691.
- ↑ He F, Chou CJ, Scheiner M, Poeta E, Yuan Chen N, Gunesch S, et al. (April 2021). "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. doi:10.1021/acs.jmedchem.0c01940. hdl:11585/845023. PMID 33769811.
- ↑ Ma J, Huo X, Jarpe MB, Kavelaars A, Heijnen CJ (October 2018). "Pharmacological inhibition of HDAC6 reverses cognitive impairment and tau pathology as a result of cisplatin treatment". Acta Neuropathologica Communications. 6 (1) 103. doi:10.1186/s40478-018-0604-3. PMC 6166273. PMID 30270813.
- ↑ Wang D, Wang B, Liu Y, Dong X, Su Y, Li S (November 2019). "Protective Effects of ACY-1215 Against Chemotherapy-Related Cognitive Impairment and Brain Damage in Mice". Neurochemical Research. 44 (11): 2460–2469. doi:10.1007/s11064-019-02882-6. PMID 31571096.