SOBETIROME

Details

Stereochemistry	ACHIRAL
Molecular Formula	C20H24O4
Molecular Weight	328.4022
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)C1=C(O)C=CC(CC2=C(C)C=C(OCC(O)=O)C=C2C)=C1

InChI

InChIKey=QNAZTOHXCZPOSA-UHFFFAOYSA-N

InChI=1S/C20H24O4/c1-12(2)17-9-15(5-6-19(17)21)10-18-13(3)7-16(8-14(18)4)24-11-20(22)23/h5-9,12,21H,10-11H2,1-4H3,(H,22,23)

HIDE SMILES / InChI

Molecular Formula	C20H24O4
Molecular Weight	328.4022
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26565124 | http://adisinsight.springer.com/drugs/800021148 | https://www.ncbi.nlm.nih.gov/pubmed/21208155 | https://www.ncbi.nlm.nih.gov/pubmed/19002578

Sobetirome (3,5-dimethyl-4[(4'-hydroxy-3'-isopropylbenzyl)-phenoxy] acetic acid, also known as GC-1 and QRX-431, is a member of a class of compounds known as selective thyromimetics. It was firstly developed by Thomas Scanlan’s group at the University of California-San Francisco (UCSF) in 1995. Sobetirome binds selectively to the main hepatic form of thyroid hormone (TH) receptor, TRβ1, compared to TRα1, which is principally responsible for thyrotoxic effects on heart, muscle and bone. Sobetirome also preferentially accumulates in liver. It was originally envisaged that sobetirome could be used to stimulate hepatic pathways that lower cholesterol without harmful side effects and might be used in conjunction with statins. Indeed, sobetirome progressed through preclinical animal studies and Phase I human clinical trials with excellent results and without obvious harmful side effects. Sobetirome had been in phase I clinical trials for the treatment of lipid metabolism disorders and obesity. However, this research has been discontinued.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Thyroid hormone receptor beta-1 25 Target ID: CHEMBL1947 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19002578 \| https://www.ncbi.nlm.nih.gov/pubmed/26565124 \| https://www.ncbi.nlm.nih.gov/pubmed/9653548 \| https://www.ncbi.nlm.nih.gov/pubmed/23667826	Agonist 2678		7.0 nM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Obesity 203 Sources: http://adisinsight.springer.com/drugs/800021148 https://www.ncbi.nlm.nih.gov/pubmed/26565124	Primary		Phase I 428	Unknown Approved Use Unknown
X-linked adrenoleukodystrophy 8 Sources: http://adisinsight.springer.com/drugs/800021148 https://clinicaltrials.gov/ct2/show/NCT03196765	Primary		Phase II 1132	Unknown Approved Use Unknown

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY431259	https://www.001chemical.com/chem/search?q=DY431259
1PlusChem LLC	1P002LMQ	https://www.1pchem.com/search?query=1P002LMQ
A2B Chem	AB20546	http://a2bchem.com/prod/AB20546
AK Scientific	4054AH	https://aksci.com/item_detail.php?cat=4054AH
ApexBio Technology	A3828	https://www.apexbt.com/catalogsearch/result/?q=A3828
BLD Pharm	BD630538	http://www.bldpharm.com/search/Search.html?keyword=BD630538
Chem Scene	CS-0956	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0956
Lab Network	LN01343277	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01343277
MedChem Express	HY-14823	https://www.medchemexpress.com/search.html?q=HY-14823&ft=&fa=&fp=
MolPort	MolPort-035-765-758	https://www.molport.com/shop/molecule-link/MolPort-035-765-758
Molcore	MC431259	http://www.molcore.com/CatMC431259.html
MuseChem	I002623	https://www.musechem.com/product/I002623.html
ShangHai Biochempartner	BCP23779	http://www.biochempartner.com/search_BCP23779
TargetMol	T5313	https://www.targetmol.com/search?keyword=T5313
Tocris	4554	https://www.tocris.com/search.php?Type=QuickSearch&Value=4554
Wonderchem	WC-009UTB	http://www.wonder-chem.com/search.html?text=WC-009UTB
eMolecules	44811492	https://orderbb.emolecules.com/search/#?query=44811492
mcule	MCULE-6551938322	https://mcule.com/MCULE-6551938322/

PubMed

Title	Date	PubMed
Opiate-dependent modulation of adenylate cyclase.	1977 Aug	269396
Binding of 3,5,3'-triiodothyronine (T3) and its analogs to the in vitro translational products of c-erbA protooncogenes: differences in the affinity of the alpha- and beta-forms for the acetic acid analog and failure of the human testis and kidney alpha-2 products to bind T3.	1990 Feb	2158622
A high-affinity subtype-selective agonist ligand for the thyroid hormone receptor.	1998 Jun	9653548
Regulation of thyroid hormone receptor isoforms in physiological and pathological cardiac hypertrophy.	2001 Sep 28	11577024
Structural basis of GC-1 selectivity for thyroid hormone receptor isoforms.	2008 Jan 31	18237438
TRbeta is the critical thyroid hormone receptor isoform in T3-induced proliferation of hepatocytes and pancreatic acinar cells.	2010 Oct	20638743

Patents

Sample Use Guides

In Vivo Use Guide

Single oral doses of 1, 5, 25, 50, 75, 150, 300, and 450 meg of sobetirome have been investigated in a randomized, double-blind, placebo controlled, cross-over, single rising dose safety and tolerance study in healthy male volunteers. All doses were well tolerated with no notable safety concerns. The second phase 1 study involved multiple oral doses of 10, 30, 70 and 100 meg of sobetirome administered daily for 14 days in a randomized, double-blind, placebo controlled, rising multiple-dose safety and tolerance study in healthy male volunteers.

Route of Administration: Oral

In Vitro Use Guide

Sobetirome (30 nM) promotes oligodendrogenesis in murine DsRed+ cells without significantly decreasing mitogen-induced proliferation.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 16:25:25 UTC 2023` Edited by `admin` on `Sat Dec 16 16:25:25 UTC 2023`
Record UNII	XQ31741E9Q
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

SOBETIROME

Official Name

English

Sobetirome [WHO-DD]

Common Name

English

SOBETIROME [USAN]

Common Name

English

(4-{[4-Hydroxy-3-(1-methylethyl)phenyl]methyl}-3,5-dimethylphenoxy)acetic acid

Systematic Name

English

GC-1

Code

English

QRX-431

Code

English

sobetirome [INN]

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

334811