Sobetirome (GC-1)

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Overview

Sobetirome, also called GC-1 and later QRX-431, is a synthetic analog of thyroid hormone made in Thomas Scanlan laboratory and first described in 1998 as a high-affinity, subtype-selective agonist for the thyroid hormone receptor (PMID: 9653548). The idea behind it is straightforward: thyroid hormone lowers cholesterol and raises metabolic rate, but it also speeds the heart, and the receptor that drives the heart effects is a different subtype from the one that drives the liver effects. A drug selective for the beta subtype should separate the two. QuatRx Pharmaceuticals developed it as a cholesterol-lowering agent and the program was later reviewed as a case history in drug discovery (PMID: 19002578). The animal data support the separation. In hypothyroid mice and hypercholesteremic rats, GC-1 lowered triglycerides better than triiodothyronine and lowered cholesterol comparably, but did not raise heart rate or normalize the cardiac genes that thyroid hormone acts on (PMID: 10965874). In cholesterol-fed rats it lowered cholesterol at roughly 30 times lower exposure than needed to cause a fast heart rate, and in cynomolgus monkeys it lowered cholesterol and lipoprotein(a) with no tachycardia and about a 4 percent reduction in body weight (PMID: 14701670). In euthyroid mice it reduced serum lipids and stimulated steps of reverse cholesterol transport (PMID: 16006512). For body composition, the relevant rat study ran six weeks and compared GC-1 with triiodothyronine at matched doses. Oxygen consumption rose 50 to 70 percent with both. Control rats gained about 80 percent more fat mass, triiodothyronine-treated rats lost 70 to 90 percent, and GC-1-treated rats lost about 20 percent. The difference that matters is muscle: triiodothyronine shrank individual skeletal muscles while GC-1 barely did, and GC-1 did not drive up food intake the way triiodothyronine did (PMID: 17400799). There is a safety signal that gets left out of marketing. In rats, GC-1 was a strong mitogen: it stimulated hepatocyte proliferation without tissue injury and induced massive pancreatic acinar cell proliferation (PMID: 16574785). That is a proliferation finding in two organs, in a compound intended for chronic use. Human evidence is thin. Phase 1 single-dose and two-week multiple-dose studies in healthy volunteers were announced by the sponsor as showing LDL cholesterol reductions, but those results were reported in company announcements rather than a peer-reviewed trial publication, and the cholesterol program did not continue. Sobetirome was later picked up for X-linked adrenoleukodystrophy, but both registered trials, NCT01787578 and NCT03196765, were withdrawn without enrolling a single participant. More recent work has focused on the brain-penetrant prodrug Sob-AM2 in animal models of demyelination (PMID: 29845892; PMID: 36792926). Capsules sold as sobetirome are an unapproved thyroid-active drug with no completed human trial behind them.

Potential Research Fields

Contraindications

Research Disclaimer

This interaction data is compiled from published research and community reports. It may not be exhaustive. Always consult a healthcare professional before combining compounds.

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Tracking since Sep 7, 2026 · 1 data point

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