PROFILPELAJAR.COM

Ricolinostat

Ricolinostat
Clinical data
Other namesRocilinostat; ACY-1215; ACY1215; ACY-63; ACY63
Routes of
administration		Oral[1]
Drug classHistone deacetylase inhibitor; HDAC6 inhibitor
Identifiers
  • N-[7-(hydroxyamino)-7-oxoheptyl]-2-(N-phenylanilino)pyrimidine-5-carboxamide
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
Chemical and physical data
FormulaC24H27N5O3
Molar mass433.512 g·mol−1
3D model (JSmol)
  • C1=CC=C(C=C1)N(C2=CC=CC=C2)C3=NC=C(C=N3)C(=O)NCCCCCCC(=O)NO
  • InChI=1S/C24H27N5O3/c30-22(28-32)15-9-1-2-10-16-25-23(31)19-17-26-24(27-18-19)29(20-11-5-3-6-12-20)21-13-7-4-8-14-21/h3-8,11-14,17-18,32H,1-2,9-10,15-16H2,(H,25,31)(H,28,30)
  • Key:QGZYDVAGYRLSKP-UHFFFAOYSA-N

Ricolinostat (INNTooltip International Nonproprietary Name, USANTooltip 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]

Pharmacology

Ricolinostat activities
Enzyme IC50Tooltip 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]

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. ^ a b c d e f "Regenacy Pharmaceuticals". AdisInsight. 28 February 2025. Retrieved 3 August 2026.
  2. ^ a b c d 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.
  3. ^ 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.
  4. ^ a b 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.
  5. ^ 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.
  6. ^ 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.
  7. ^ 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.
  8. ^ 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.
  9. ^ 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.
  10. ^ 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.

Content Disclaimer

Informasi ini disarikan dari Wikipedia dan disajikan kembali untuk tujuan edukasi. Konten tersedia di bawah lisensi CC BY-SA 3.0. Kami tidak bertanggung jawab atas ketidakakuratan data yang bersumber dari kontribusi publik tersebut.

  1. The information displayed on this website is sourced in part or in whole from Wikipedia and has been adapted for the purpose of restating it. We strive to provide accurate and relevant information, however:
  2. There is no guarantee of absolute accuracy. Wikipedia is an open, collaborative project that can be edited by anyone, so information is subject to change.
  3. It is not intended to constitute professional advice. The content displayed is for informational and educational purposes only. For important decisions (e.g., medical, legal, or financial), please consult a professional.
  4. Content copyright. Wikipedia is licensed under the Creative Commons Attribution-ShareAlike License (CC BY-SA). This means that content may be reused with appropriate attribution and shared under a similar license.
  5. Responsible use. Any risk arising from the use of information from this website is entirely the responsibility of the user.