GC-1 (Sobetirome)
Research Guide

Research Overview

GC-1, more formally named sobetirome (INN/USAN), is a synthetic small-molecule thyromimetic studied as a selective agonist of thyroid hormone receptor beta (TRbeta). It is a halogen-free diarylmethane analog of thyroid hormone and, unlike many compounds in this catalog, it is a small molecule rather than a peptide. Identity is well characterized in public chemistry databases: PubChem lists it under CID 9862248 with the CAS number 211110-63-3.

Research interest in GC-1 centers on its reported preference for TRbeta over TRalpha. In published binding studies it showed roughly 10-fold lower affinity for human TRalpha1 than for human TRbeta1, a difference attributed to a single differing residue in the receptor ligand-binding pocket. Because thyroid hormone signaling in the heart is mediated largely through TRalpha, this receptor-subtype preference has made GC-1 a widely used tool compound for probing tissue-selective thyroid-hormone-like effects in cell and animal models.

This page compiles verified identity data, the reported mechanism, and the preclinical research literature for laboratory reference only. It describes what has been studied in cells and animals. It does not describe any human effect, dose, or use. Note that 'Sobertime' as it sometimes appears in supplier notes is a misspelling; the correct database name is Sobetirome.

Mechanism Summary

Mechanisms reported in the in-vitro and preclinical research literature include:

• GC-1 (sobetirome) is reported to act as a selective agonist of thyroid hormone receptor beta (TRbeta), a member of the nuclear-receptor superfamily. In binding studies it showed roughly 10-fold lower affinity for human TRalpha1 than for human TRbeta1 (PMC2275733), the structural basis for its use as a TRbeta-preferring probe.
• The reported structural explanation is a single differing amino acid in the ligand-binding pocket: asparagine 331 in TRbeta versus serine 277 in TRalpha. In TRbeta, Asn331 is described as forming a stabilizing hydrogen bond with Arg282 that locks in the productive ligand-binding conformation, while the smaller Ser277 in TRalpha cannot provide equivalent stabilization. Because GC-1 lacks the amino-acid side chain present on the natural hormone T3, this differential stabilization is reported to become pronounced (PMC2275733).
• As a nuclear-receptor ligand, on binding TRbeta the compound is reported to modulate thyroid-hormone-responsive gene transcription. In animal models this has been described as recapitulating selective, liver-directed thyroid-hormone-like effects such as triglyceride and cholesterol lowering, while producing markedly less cardiac stimulation than T3, with no reported increase in heart rate at doses that lowered lipids (PMID 10965874). The reduced cardiac effect is attributed to both TRbeta selectivity and reported preferential hepatic accumulation.
• In the central nervous system, TRbeta activation by GC-1 has been reported in vitro and in developmental-myelination mouse models to promote oligodendrocyte precursor cell differentiation and expression of the myelin proteins MBP, CNP, and MAG (PMID 24863526). All of the above is in-vitro and preclinical mechanism only; no human efficacy is described or implied.

Reference Data

Identity values are compiled from public chemistry databases and vendor documentation. Confirm the exact salt form, molecular weight, and purity for a given batch against its Certificate of Analysis (COA).

Research Applications

In laboratory research, GC-1 (Sobetirome) is studied in contexts such as:

• Studied in vitro and in rodent and human oligodendrocyte progenitor cell models as a reported driver of oligodendrocyte differentiation and developmental myelination (PMID 24863526)
• Investigated preclinically for remyelination via the CNS-penetrant amide prodrug Sob-AM2, reported to promote myelin repair in mouse demyelination models and framed in the literature as a candidate approach for demyelinating disease research (PMID 32733906 review)
• Investigated as a lipid-modulating thyromimetic in hypothyroid mice and hypercholesterolemic rats, reported to lower triglycerides and cholesterol without raising heart rate versus T3 (PMID 10965874)
• Studied in rats for effects on energy expenditure and body composition, reported to increase oxygen consumption and limit fat-mass accumulation, framed as a metabolic-syndrome research candidate (PMID 17400799)
• Investigated in X-linked adrenoleukodystrophy (X-ALD) models, where sobetirome and Sob-AM2 were reported to upregulate the peroxisomal transporter Abcd2 and lower very-long-chain fatty acids in the CNS as pharmacological complementation for ABCD1 loss (PMID 32169163)
• Reported to induce hepatocyte and pancreatic acinar cell proliferation in rat liver and pancreas without tissue injury, studied in the context of liver regeneration research (PMID 16574785)
• Investigated as an antitumor agent in preclinical cancer models, reported to reduce growth of Met-beta-catenin-driven hepatocellular carcinoma in mice (PMID 28807594) and to inhibit colorectal tumor growth in a syngeneic mouse model (PMID 35473566)
• Note on clinical status: two early-stage clinical studies in adrenoleukodystrophy were registered (NCT01787578, a Phase 1 sobetirome study; NCT03196765, a Phase 1/2 NV1205 study), but both were WITHDRAWN with zero enrollment, so no human outcome data exist

Storage Information

• Handle and store as a lyophilized or solid small-molecule research chemical. Confirm the exact recommended storage temperature, desiccation, and light-protection conditions against the batch COA and supplier data sheet, since these were not confirmed from a retrieved primary source in this compilation.
• For general cold-chain and desiccation practice, see the Lyophilized Storage Guide.
• If preparing a stock solution for in-vitro work, use the Reconstitution Calculator to plan concentrations. Note that GC-1 is a small molecule, not a peptide: appropriate solvents (for example DMSO or ethanol versus aqueous buffer) and solubility limits should be confirmed against the COA or supplier data sheet before reconstitution.