Palovarotene
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MedKoo CAT#: 319875

CAS#: 410528-02-8

Description: Palovarotene, also known as RO-3300074 and R-667, is a highly selective retinoic acid receptor gamma (RAR-γ) agonist that is under investigation as a potential treatment for emphysema. Phase I clinical trials of palovarotene in patients with emphysema demonstrated that the drug is well tolerated, with improvements observed in markers of emphysema progression. Emphysema is characterized by the destruction of alveoli and alveolar ducts within the lungs. Retinoid signaling is believed to play a role in alveologenesis, with the retinoic acid receptor gamma thought to be required for alveolar formation.


Chemical Structure

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Palovarotene
CAS# 410528-02-8

Theoretical Analysis

MedKoo Cat#: 319875
Name: Palovarotene
CAS#: 410528-02-8
Chemical Formula: C27H30N2O2
Exact Mass: 414.23
Molecular Weight: 414.549
Elemental Analysis: C, 78.23; H, 7.29; N, 6.76; O, 7.72

Price and Availability

Size Price Availability Quantity
5mg USD 245
10mg USD 415
25mg USD 730
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Synonym: RO-3300074; RO 3300074; RO3300074; R-667; R 667; R667; Palovarotene

IUPAC/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

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+

SMILES Code: O=C(O)C1=CC=C(/C=C/C2=C(CN3N=CC=C3)C=C4C(C)(C)CCC(C)(C)C4=C2)C=C1

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:

Product Data:
Biological target: Palovarotene is a nuclear retinoic acid receptor γ (RAR-γ) agonist.
In vitro activity: TBD
In vivo activity: This study tested Palovarotene in our validated rat trauma-induced HO (heterotopic ossification) model that involves blast-related limb injury, femoral fracture, quadriceps crush injury, amputation and infection with methicillin-resistant Staphylococcus aureus from combat wound infections. Palovarotene was given orally for 14days at 1mg/kg/day starting on post-operative day (POD) 1 or POD-5, and HO amount, wound dehiscence and related processes were monitored for up to 84days post injury. Compared to vehicle-control animals, Palovarotene significantly decreased HO by 50 to 60% regardless of when the treatment started and if infection was present. Histological analyses showed that Palovarotene reduced ectopic chondrogenesis, osteogenesis and angiogenesis forming at the injury site over time, while fibrotic tissue was often present in place of ectopic bone. Reference: Bone. 2016 Sep;90:159-67. https://pubmed.ncbi.nlm.nih.gov/27368930/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMF 25.0 60.31
DMSO 22.5 54.28
DMSO:PBS (pH 7.2) (1:2) 0.3 0.72
Ethanol 3.0 7.24

Preparing Stock Solutions

The following data is based on the product molecular weight 414.55 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Chakkalakal SA, Uchibe K, Convente MR, Zhang D, Economides AN, Kaplan FS, Pacifici M, Iwamoto M, Shore EM. 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. doi: 10.1002/jbmr.2820. Epub 2016 Mar 12. PMID: 26896819; PMCID: PMC4992469. 2. Pavey GJ, Qureshi AT, Tomasino AM, Honnold CL, Bishop DK, Agarwal S, Loder S, Levi B, Pacifici M, Iwamoto M, Potter BK, Davis TA, Forsberg JA. 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. doi: 10.1016/j.bone.2016.06.014. Epub 2016 Jun 28. PMID: 27368930; PMCID: PMC5546218.
In vitro protocol: TBD
In vivo protocol: 1. Chakkalakal SA, Uchibe K, Convente MR, Zhang D, Economides AN, Kaplan FS, Pacifici M, Iwamoto M, Shore EM. 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. doi: 10.1002/jbmr.2820. Epub 2016 Mar 12. PMID: 26896819; PMCID: PMC4992469. 2. Pavey GJ, Qureshi AT, Tomasino AM, Honnold CL, Bishop DK, Agarwal S, Loder S, Levi B, Pacifici M, Iwamoto M, Potter BK, Davis TA, Forsberg JA. 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. doi: 10.1016/j.bone.2016.06.014. Epub 2016 Jun 28. PMID: 27368930; PMCID: PMC5546218.

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1. Hind, M., and Stinchcombe, S. Palovarotene, a novel retinoic acid receptor gamma agonist for the treatment of emphysema. Curr. Opin. Investig. Drugs 10(11), 1243-1250 (2009).

2. Sinha, S., Uchibe, K., Usami, Y., et al. Effectiveness and mode of action of a combination therapy for heterotopic ossification with a retinoid agonist and an anti-inflammatory agent. Bone 90, 59-68 (2016).

3. Lees-Shepard, J.B., Nicholas, S.-A.E., Stoessel, S.J., et al. Palovarotene reduces heterotopic ossification in juvenile FOP mice but exhibits pronounced skeletal toxicity. Elife 7, e40814 (2018).

4. Chakkalakal, S.A., Uchibe, K., Convente, M.R., et al. Palovarotene inhibits heterotopic ossification and maintains limb mobility and growth in mice with the human ACVR1R206H fibrodysplasia ossificans progressiva (FOP) mutation. J. Bone Miner. Res. 31(9), 1666-1675 (2016).

5. Pavey, G.J., Qureshi, A.T., Tomasino, A.M., et al. Targeted stimulation of retinoic acid receptor-γ mitigates the formation of heterotopic ossification in an established blast-related traumatic injury model. Bone 90, 159-167 (2016).