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), FDA (2023))
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 [1,8], 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) [6,9].
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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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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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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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, 49 (8): 881-892. [PMID:35638441]
5. Pignolo RJ, Hsiao EC, Al Mukaddam M, Baujat G, Berglund SK, Brown MA, Cheung AM, De Cunto C, Delai P, Haga N et al.. (2023)
Reduction of New Heterotopic Ossification (HO) in the Open-Label, Phase 3 MOVE Trial of Palovarotene for Fibrodysplasia Ossificans Progressiva (FOP).
J Bone Miner Res, 38 (3): 381-394. [PMID:36583535]
6. Pignolo RJ, Pacifici M. (2021)
Retinoid Agonists in the Targeting of Heterotopic Ossification.
Cells, 10 (11): 3245. [PMID:34831466]
7. 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]
8. 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]
9. 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]
10. 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]