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
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
Biological target:
Palovarotene is a nuclear retinoic acid receptor γ (RAR-γ) agonist.
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/
|
Solvent |
mg/mL |
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 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
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.
| 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 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.
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).
