palovarotene

palovarotene Property

Melting point:

249-252°C

Boiling point:

592.3±50.0 °C(Predicted)

Density 

1.11

storage temp. 

Refrigerator

solubility 

DMSO (Slightly), Ethyl Acetate (Slightly, Heated), Methanol (Slightly, Heated)

pka

4.26±0.10(Predicted)

form 

Solid

color 

White to Off-White

InChIKey

YTFHCXIPDIHOIA-DHZHZOJOSA-N

SMILES

C(O)(=O)C1=CC=C(/C=C/C2=C(CN3C=CC=N3)C=C3C(=C2)C(C)(C)CCC3(C)C)C=C1

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P301+P312IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.

P302+P352IF ON SKIN: wash with plenty of soap and water.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

palovarotene Chemical Properties,Usage,Production

Description

Palovarotene an orally bioavailable retinoic acid receptor γ (RARγ) agonist. It increases retinoic acid response element (RARE) activity and decreases NF-κB activity induced by IL-1β in primary mouse stromal cells in reporter assays when used at a concentration of 60 nM. Palovarotene (10 nM) inhibits activin A-induced chondrogenic and osteogenic differentiation of mouse fibro/adipogenic progenitors (FAPs) expressing a mutated form of human activin A receptor type I (ACVR1^R206H). It inhibits heterotopic ossification and preserves limb movement and growth in a ACVR1^R206H fibrodysplasia ossificans progressiva (FOP) mouse model. Palovarotene (1 mg/kg per day for 14 days) decreases heterotopic ossification by 50 to 60% in a rat model of traumatic blast injury.

Uses

Palovarotene, is a highly selective retinoic acid receptor gamma (RAR-γ) agonist that is under investigation as a potential treatment for emphysema.

Definition

ChEBI: Palovarotene is a stilbenoid.

in vivo

References

[1] MATTHEW HIND S S. Palovarotene, a novel retinoic acid receptor gamma agonist for the treatment of emphysema.[J]. Current opinion in investigational drugs, 2009, 10 11: 1243-1250.
[2] SAYANTANI SINHA. Effectiveness and mode of action of a combination therapy for heterotopic ossification with a retinoid agonist and an anti-inflammatory agent[J]. Bone, 2016, 90: Pages 59-68. DOI: 10.1016/j.bone.2016.02.008
[3] JOHN B LEES-SHEPARD. Palovarotene reduces heterotopic ossification in juvenile FOP mice but exhibits pronounced skeletal toxicity.[J]. eLife, 2018. DOI: 10.7554/elife.40814
[4] SALIN A CHAKKALAKAL. Palovarotene Inhibits Heterotopic Ossification and Maintains Limb Mobility and Growth in Mice With the Human ACVR1R206H Fibrodysplasia Ossificans Progressiva (FOP) Mutation[J]. Journal of Bone and Mineral Research, 2016, 31 9: 1666-1675. DOI: 10.1002/jbmr.2820
[5] GABRIEL J. PAVEY . Targeted stimulation of retinoic acid receptor-γ mitigates the formation of heterotopic ossification in an established blast-related traumatic injury model[J]. Bone, 2016, 90: Pages 159-167. DOI: 10.1016/j.bone.2016.06.014