What is Trodusquemine (MSI-1436)?
Trodusquemine is a naturally occurring aminosterol that was originally isolated from the liver of the dogfish shark, Squalus acanthias [1.6.5, 1.6.9]. It functions as a potent and highly selective allosteric inhibitor of protein tyrosine phosphatase 1B (PTP1B) [1.4.5, 1.6.2]. This enzyme, PTP1B, is a significant negative regulator of both the insulin and leptin signaling pathways in the body [1.4.4, 1.4.6]. By inhibiting PTP1B, trodusquemine enhances these signals, which play crucial roles in metabolism, appetite control, and cellular function [1.4.1]. Due to this unique mechanism, the compound has been investigated for a wide range of therapeutic applications, including obesity, type 2 diabetes, Alzheimer's disease, heart disease, and even certain types of cancer [1.2.8, 1.4.8].
The Central Question: Is Trodusquemine Available in the USA?
Despite promising preclinical data and some early human trials, the direct answer is no. As of September 2025, trodusquemine is not an FDA-approved drug and cannot be legally prescribed or sold for human use in the United States [1.3.1]. It is available from some commercial suppliers, but strictly for research purposes [1.2.1].
The development of trodusquemine has had a complicated history. Initial Phase 1 clinical trials for obesity and type 2 diabetes were completed and showed the drug was well-tolerated [1.5.1, 1.5.7]. However, the company sponsoring these trials, Genaera Corporation, ceased operations in 2009 due to financial difficulties and sold its assets [1.2.1, 1.6.1]. The rights were acquired by other companies, but subsequent development has been slow and has not led to late-stage clinical trials for its primary metabolic indications [1.2.1]. Several planned phase II trials were halted due to these financial issues with the original developer [1.4.8].
The Science Behind Trodusquemine: How PTP1B Inhibition Works
The therapeutic potential of trodusquemine lies in its ability to inhibit PTP1B. This enzyme is found in high levels in the adipose tissue and skeletal muscle of obese, insulin-resistant individuals [1.4.5].
- Insulin and Leptin Pathways: Insulin and leptin are hormones critical for regulating blood sugar and appetite. PTP1B acts as a brake on their signaling pathways. When PTP1B dephosphorylates (inactivates) the insulin and leptin receptors, it dampens their effect [1.4.6]. By inhibiting PTP1B, trodusquemine essentially 'releases the brake,' allowing for stronger and more sustained signaling. This can lead to improved insulin sensitivity, reduced appetite, and subsequent weight loss [1.4.1, 1.4.9].
- Dual-Action Potential: A key feature of trodusquemine is its ability to act both in the brain (centrally) and in the rest of the body (peripherally) [1.6.2]. Central action in the hypothalamus can suppress appetite, while peripheral action can improve how tissues like muscle and liver respond to insulin [1.4.1, 1.5.1].
- Neuroprotection and Regeneration: Beyond metabolism, PTP1B is implicated in neuroinflammation and endoplasmic reticulum (ER) stress, processes linked to Alzheimer's disease [1.4.5]. Preclinical studies in mice suggest that inhibiting PTP1B with trodusquemine can restore memory deficits, reduce inflammation in the hippocampus, and even protect against the buildup of toxic protein aggregates associated with the disease [1.4.3, 1.5.2]. Additionally, studies in animals have shown it can promote tissue regeneration, including in the heart after ischemic injury [1.6.5].
Comparison with Current FDA-Approved Therapies
While trodusquemine remains investigational, the landscape for obesity and metabolic disease treatments has evolved significantly. The most prominent current therapies are GLP-1 receptor agonists.
| Feature | Trodusquemine (Investigational) | GLP-1 Agonists (e.g., Semaglutide) |
|---|---|---|
| Mechanism of Action | Inhibits the PTP1B enzyme, enhancing insulin and leptin sensitivity [1.4.1]. | Mimics the GLP-1 hormone to increase insulin secretion, slow stomach emptying, and reduce appetite [1.5.4]. |
| FDA Approval Status | Not Approved. Available for research use only [1.3.1]. | Approved for type 2 diabetes and/or weight management. |
| Primary Targets | Obesity, Type 2 Diabetes, Alzheimer's (preclinical) [1.2.8, 1.4.8]. | Type 2 Diabetes, Weight Management. Also being studied for dementia [1.5.4, 1.5.6]. |
| Administration | Intravenous or intraperitoneal injection in trials [1.2.1, 1.4.9]. | Typically subcutaneous injection (daily or weekly) or oral pill [1.3.4]. |
| Development Status | Stalled after Phase 1 trials due to sponsor's financial issues; some ongoing preclinical research [1.2.1, 1.4.8]. | Widely available commercially and undergoing extensive further clinical trials for other indications [1.5.4]. |
The Future of Trodusquemine
The path for trodusquemine to become a marketable drug in the USA is long and uncertain. For it to become available, a pharmaceutical company would need to:
- Acquire or confirm the rights to the compound.
- Invest significant capital to resume clinical development.
- Successfully conduct Phase 2 and Phase 3 clinical trials to prove its safety and efficacy in humans for a specific condition.
- Submit a New Drug Application (NDA) to the FDA and gain approval.
While research continues to explore its potential, particularly in areas like Alzheimer's and tissue regeneration, there is currently no clear indication that large-scale trials for its original targets of obesity and diabetes will resume soon [1.2.1, 1.2.7]. Researchers at the University of Aberdeen and The Ottawa Hospital have expressed hope that promising preclinical findings might attract funding for future human trials [1.2.7, 1.5.2].
Conclusion
To summarize, is trodusquemine available in the USA? No, not for public or clinical use. It is a fascinating compound with a unique mechanism of action that has shown considerable promise in laboratory and animal studies for treating a host of major diseases. However, its journey to the pharmacy shelf was cut short by financial and corporate hurdles over a decade ago. While its story is a compelling example of the challenges in drug development, patients hoping for a new treatment must look to FDA-approved alternatives, as trodusquemine remains, for now, a subject of scientific research rather than a clinical reality. Its future hinges on new investment and renewed interest in bringing this shark-derived molecule back into the clinical trial pipeline.
