Palovarotene

Alias: RO-3300074; R-667; RO 3300074; R 667; RO3300074; R667; Sohonos
Cat No.:V3434 Purity: ≥98%
Palovarotene (formerly RO-3300074; R-667) is a novel, potent and highly selective retinoic acid receptor gamma (RAR-γ) agonist that is being investigated as a potential treatment for emphysema.
Palovarotene Chemical Structure CAS No.: 410528-02-8
Product category: RAR RXR
This product is for research use only, not for human use. We do not sell to patients.
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description

Palovarotene (formerly RO-3300074; R-667; Sohonos) is a novel, potent and highly selective retinoic acid receptor gamma (RAR-γ) agonist that is being investigated as a potential treatment for emphysema. Palovarotene effectively inhibited HO in injury-induced and genetic mouse models of the disease. It additionally prevents spontaneous HO, using a novel conditional-on knock-in mouse line carrying the human ACVR1(R206H) mutation for classic FOP. In addition, palovarotene restored long bone growth, maintained growth plate function, and protected growing mutant neonates when given to lactating mothers. Importantly, palovarotene maintained joint, limb, and body motion, providing clear evidence for its encompassing therapeutic potential as a treatment for FOP. Palovarotene (Sohonos) was approved in 2023 by FDA for treating Fibrodysplasia ossificans progressiva.

Biological Activity I Assay Protocols (From Reference)
ln Vivo
Palovarotene inhibits trauma-induced ectopic bone development and mediates osteogenesis and post-traumatic bone formation. Palovarotene is used to monitor intraoperative and subcutaneous heterotopic ossification (HO) following trauma. During the first 14 days of the trial, palovarotene was given orally at a dose of 1 mg/kg/day beginning on day 1 or day 5. H2O volume, wound breakdown, and associated processes were periodically observed for up to 84 days. When compared to vehicle animals, palovarotene dramatically lowers H2O by 50% to 60% per dosage [1]. Half of the Acvr1cR206H/+ mice got daily treatment with palovarotene for 14 days starting on the first day of damage, while the other half were given a vehicle as a control. Large tissue masses were seen in the target legs of the vector-acvr1cR206H/+ mutation, according to analysis of mCT and 3D image formation reconstructions after 14 days. However, palovarotene-treated partners showed significantly lower HO, as measured by bone volume/total volume formation, which improved by more than 80%[2].
References
[1]. Pavey GJ, et al. Targeted stimulation of retinoic acid receptor-γ mitigates the formation of heterotopic ossification in an established blast-related traumatic injury model. Bone. 2016 Sep;90:159-67.
[2]. Chakkalakal SA, et al. Palovarotene Inhibits Heterotopic Ossification and Maintains Limb Mobility and Growth in Mice With the Human ACVR1(R206H) Fibrodysplasia Ossificans Progressiva (FOP) Mutation. J Bone Miner Res. 2016 Sep;31(9):1666-75.
[3]. Lees-Shepard JB, et al. Palovarotene reduces heterotopic ossification in juvenile FOP mice but exhibits pronounced skeletal toxicity. Elife. 2018 Sep 18;7. pii: e40814
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C27H30N2O2
Molecular Weight
414.54
CAS #
410528-02-8
SMILES
O=C(O)C1=CC=C(/C=C/C2=C(CN3N=CC=C3)C=C4C(C)(C)CCC(C)(C)C4=C2)C=C1
InChi Key
YTFHCXIPDIHOIA-DHZHZOJOSA-N
InChi Code
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+
Chemical Name
4-((1E)-2-(5,5,8,8-Tetramethyl-3-(1H-pyrazol-1-ylmethyl)-5,6,7,8-tetrahydronaphthalen-2-yl)ethenyl)benzoic acid
Synonyms
RO-3300074; R-667; RO 3300074; R 667; RO3300074; R667; Sohonos
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO : ~25 mg/mL (~60.31 mM)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 2.4123 mL 12.0616 mL 24.1231 mL
5 mM 0.4825 mL 2.4123 mL 4.8246 mL
10 mM 0.2412 mL 1.2062 mL 2.4123 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

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Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

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Biological Data
  • Palovarotene


    Injury-induced heterotopic ossification inAcvr1cR206H/+mutant mice is inhibited by the RARγ agonist Palovarotene.

  • Palovarotene


    Palovarotene preserves long bone growth and growth plate organization inPrrx1-R206Hmice.2016 Sep;31(9):1666-75.

  • Palovarotene


    Chondrocyte proliferation and progression are altered inPrrx1-R206Hgrowth plates.2016 Sep;31(9):1666-75.

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