Palovarotene

Details

Stereochemistry	ACHIRAL
Molecular Formula	C27H30N2O2
Molecular Weight	414.5393
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1(C)CCC(C)(C)C2=C1C=C(CN3C=CC=N3)C(\C=C\C4=CC=C(C=C4)C(O)=O)=C2

InChI

InChIKey=YTFHCXIPDIHOIA-DHZHZOJOSA-N

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+

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19876792 | https://www.ncbi.nlm.nih.gov/pubmed/26896819 | http://www.prnewswire.com/news-releases/phase-2-part-a-open-label-extension-trial-of-palovarotene-for-treatment-of-patients-with-fibrodysplasia-ossificans-progressiva-continues-positive-trends-300429975.html

Palovarotene (R-667, RO-3300074) was developed by Roche Holding AG as a selective retinoic acid receptor gamma agonist for the treatment of 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. Unlike all-trans retinoic acid, the pharmacokinetic profile of palovarotene appears to be dose-proportional. However, those studies were discontinued. Palovarotene is also being investigated in phase II of the clinical trial in the treatment of Fibrodysplasia Ossificans Progressiva (FOP). Palovarotene received Fast Track designation from the U.S. Food and Drug Administration (FDA) and orphan designations for the treatment of FOP from both the FDA and the European Medicines Agency (EMA).

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Retinoic acid receptor gamma 18 Target ID: CHEMBL2003 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19876792	Agonist 2752

Conditions

Condition	Modality	Targets	Highest Phase	Product
Fibrodysplasia ossificans progressiva 1 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26896819	Primary		Phase II 1147	Unknown Approved Use Unknown
Emphysema 13 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19876792	Primary		Phase I 438	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
10.3 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17324249	1 mg 1 times / day multiple, oral dose: 1 mg route of administration: Oral experiment type: MULTIPLE co-administered:		PALOVAROTENE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED

AUC

Value	Dose	Co-administered	Analyte	Population
57.7 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17324249	1 mg 1 times / day multiple, oral dose: 1 mg route of administration: Oral experiment type: MULTIPLE co-administered:		PALOVAROTENE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY443083	https://www.001chemical.com/chem/search?q=DY443083
1PlusChem LLC	1P00C6XO	https://www.1pchem.com/search?query=1P00C6XO
Aceschem	ACS019963	https://www.aceschem.com/catalog/search.do?q=ACS019963
AOBIOUS INC	AOB87129	http://aobious.com/aobious/search?search_query=AOB87129
ApexBio Technology	B1175	https://www.apexbt.com/catalogsearch/result/?q=B1175
AstaTech	C15763	http://astatechinc.com/CPSResult.php?CRNO=C15763
BLD Pharm	BD630695	http://www.bldpharm.com/search/Search.html?keyword=BD630695
BOC Sciences	410528-02-8	http://www.bocsci.com/description.asp?cas=410528-02-8
Capot Chemical	34074	https://www.capotchem.com/search.do?q=34074
Chem Scene	CS-2031	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-2031
eMolecules	275156103	https://orderbb.emolecules.com/search/#?query=275156103
eMolecules	301199824	https://orderbb.emolecules.com/search/#?query=301199824
eMolecules	50282997	https://orderbb.emolecules.com/search/#?query=50282997
Excenen	EX-A3101	http://www.excenen.com/searchresultlist.php?id=EX-A3101
Hairui	HR33113	http://www.hairuichem.com/en/product/search.do?q=HR33113
mcule	MCULE-5392476065	https://mcule.com/MCULE-5392476065/
mcule	MCULE-8847772940	https://mcule.com/MCULE-8847772940/
MedChem Express	HY-14799	https://www.medchemexpress.com/search.html?q=HY-14799&ft=&fa=&fp=
Molcore	MC443083	http://www.molcore.com/CatMC443083.html
Molnova	M17504	https://www.molnova.com/en/serch-list.html?keywords=M17504
MolPort	MolPort-046-417-008	https://www.molport.com/shop/molecule-link/MolPort-046-417-008
MuseChem	I003493	https://www.musechem.com/product/I003493.html
ShangHai Biochempartner	BCP16664	http://www.biochempartner.com/search_BCP16664
TargetMol	T4538	https://www.targetmol.com/search?keyword=T4538

PubMed

Title	Date	PubMed
Potent inhibition of heterotopic ossification by nuclear retinoic acid receptor-γ agonists.	2011-04	21460849
Retinoid treatment of Emphysema in Patients on the Alpha-1 International Registry. The REPAIR study: study design, methodology and quality control of study assessments.	2010-12	20926506
Palovarotene, a novel retinoic acid receptor gamma agonist for the treatment of emphysema.	2009-11	19876792
Treatment of patients who have fibrodysplasia ossificans progressiva with isotretinoin.	1998-01	9577419

Patents

Sample Use Guides

In Vivo Use Guide

double-blind, placebo-controlled randomised study to assess the safety and efficacy of 5 mg·day(-1) palovarotene given for 1 year to 262 patients with severe α(1)-antitrypsin deficiency and emphysema confirmed by computed tomography.

Route of Administration: Oral

In Vitro Use Guide

Unknown

Name

Type

Language

Palovarotene

Official Name

English

CLM-001

Preferred Name

English

RO3300074

Code

English

RG-667

Code

English

Benzoic acid, 4-[(1E)-2-[5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-3-(1H-pyrazol-1-ylmethyl)-2-naphthalenyl]ethenyl]-

Systematic Name

English

4-{(1E)-2-[5,5,8,8-Tetramethyl-3-(1H-pyrazol-1-ylmethyl)-5,6,7,8-tetrahydronaphthalen-2-yl]ethenyl}benzoic acid

Systematic Name

English

IPN-60120

Code

English

PALOVAROTENE [USAN]

Common Name

English

RO-3300074

Code

English

palovarotene [INN]

Common Name

English

PALOVAROTENE [JAN]

Common Name

English

Palovarotene [WHO-DD]

Common Name

English

SOHONOS

Brand Name

English

IPN60120

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C804