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 | 433.512g·mol−1 |
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Ricolinostat (INN Tooltip International Nonproprietary Name, USAN Tooltip United States Adopted Name; 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]
| Enzyme | IC50 Tooltip Half-maximal inhibitory concentration (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 of ricolinostat have been reported to include diarrhea, nausea, fatigue, anemia, and hypercalcemia, among others.[4]
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, Jarpe M, van Duzer JH, Mazitschek R, Ogier WC, Cirstea D, Rodig S, Eda H, Scullen T, Canavese M, Bradner J, Anderson KC, Jones SS, Raje N (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, Supko JG, Tamang D, Yang M, Jones SS, Wheeler C, Markelewicz RJ, Lonial S (July 2017). "Ricolinostat, the First Selective Histone Deacetylase 6 Inhibitor, in Combination with Bortezomib and Dexamethasone for Relapsed or Refractory Multiple Myeloma". Clin Cancer Res. 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, Jones S, Sawas A (March 2021). "First-in-Class Selective HDAC6 Inhibitor (ACY-1215) Has a Highly Favorable Safety Profile in Patients with Relapsed and Refractory Lymphoma". 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". Nat 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". Nat 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, Xu YF, Huang L, Zhu H, Sheng SL, Qin C (2014). "Tubastatin A/ACY-1215 improves cognition in Alzheimer's disease transgenic mice". J Alzheimers Dis. 41 (4): 1193–1205. doi:10.3233/JAD-140066. PMID 24844691.
- ↑ He F, Chou CJ, Scheiner M, Poeta E, Yuan Chen N, Gunesch S, Hoffmann M, Sotriffer C, Monti B, Maurice T, Decker M (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". J Med Chem. 64 (7): 3794–3812. doi:10.1021/acs.jmedchem.0c01940. 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 Neuropathol Commun. 6 (1): 103. doi:10.1186/s40478-018-0604-3. PMC 6166273 . PMID 30270813.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ↑ 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". Neurochem Res. 44 (11): 2460–2469. doi:10.1007/s11064-019-02882-6. PMID 31571096.