palovarotene   Click here for help

GtoPdb Ligand ID: 8276

Synonyms: CLM-001 | IPN-60120 | IPN60120 | R-667 | R667 | RG-667 | Ro-3300074 | Sohonos®
Approved drug
palovarotene is an approved drug (Canada (2022))
Compound class: Synthetic organic
Comment: Palovarotene is an orally bioavailable, retinoic acid receptor gamma (RAR-γ) agonist. This compound was originally investegated for its potential to repair alveolar damage in emphysema and COPD [1,7], but it failed to demonstrate significant clinical efficacy. Ipsen acquired palovarotene when it purchased Clementia Pharmaceuticals in 2019, and they repurposed palovarotene for potential to reduce heterotopic ossification in patients with fibrodysplasia ossificans progressiva (FOP) [5,8].
2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 3
Hydrogen bond donors 1
Rotatable bonds 5
Topological polar surface area 55.12
Molecular weight 414.23
XLogP 7.85
No. Lipinski's rules broken 1
SMILES / InChI / InChIKey
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Canonical SMILES OC(=O)c1ccc(cc1)C=Cc1cc2c(cc1Cn1cccn1)C(C)(C)CCC2(C)C
Isomeric SMILES OC(=O)c1ccc(cc1)/C=C/c1cc2c(cc1Cn1cccn1)C(C)(C)CCC2(C)C
InChI InChI=1S/C27H30N2O2/c1-26(2)12-13-27(3,4)24-17-22(18-29-15-5-14-28-29)21(16-23(24)26)11-8-19-6-9-20(10-7-19)25(30)31/h5-11,14-17H,12-13,18H2,1-4H3,(H,30,31)/b11-8+
InChI Key YTFHCXIPDIHOIA-DHZHZOJOSA-N
References
1. Hind M, Stinchcombe S. (2009)
Palovarotene, a novel retinoic acid receptor gamma agonist for the treatment of emphysema.
Curr Opin Investig Drugs, 10 (11): 1243-50. [PMID:19876792]
2. Hoy SM. (2022)
Palovarotene: First Approval.
Drugs, 82 (6): 711-716. [PMID:35384641]
3. Huang J, Lin J, Li C, Tang B, Xiao H. (2022)
Palovarotene Can Attenuate Heterotopic Ossification Induced by Tendon Stem Cells by Downregulating the Synergistic Effects of Smad and NF-κB Signaling Pathway following Stimulation of the Inflammatory Microenvironment.
Stem Cells Int, 2022: 1560943. [PMID:35530413]
4. Huang J, Wu J, Lin J, Li C, Tang B, Xiao H. (2022)
Palovarotene inhibits the NF-κB signalling pathway to prevent heterotopic ossification.
Clin Exp Pharmacol Physiol, [Epub ahead of print]. DOI: 10.1111/1440-1681.13676 [PMID:35638441]
5. Pignolo RJ, Pacifici M. (2021)
Retinoid Agonists in the Targeting of Heterotopic Ossification.
Cells, 10 (11): 3245. [PMID:34831466]
6. Shimono K, Tung WE, Macolino C, Chi AH, Didizian JH, Mundy C, Chandraratna RA, Mishina Y, Enomoto-Iwamoto M, Pacifici M et al.. (2011)
Potent inhibition of heterotopic ossification by nuclear retinoic acid receptor-γ agonists.
Nat Med, 17 (4): 454-60. [PMID:21460849]
7. Stolk J, Cooper BG, Stoel B, Rames A, Rutman O, Soliman S, Stockley R. (2010)
Retinoid treatment of Emphysema in Patients on the Alpha-1 International Registry. The REPAIR study: study design, methodology and quality control of study assessments.
Ther Adv Respir Dis, 4 (6): 319-32. [PMID:20926506]
8. Wentworth KL, Masharani U, Hsiao EC. (2019)
Therapeutic advances for blocking heterotopic ossification in fibrodysplasia ossificans progressiva.
Br J Clin Pharmacol, 85 (6): 1180-1187. [PMID:30501012]
9. Zasloff MA, Rocke DM, Crofford LJ, Hahn GV, Kaplan FS. (1998)
Treatment of patients who have fibrodysplasia ossificans progressiva with isotretinoin.
Clin Orthop Relat Res, (346): 121-9. [PMID:9577419]