Thymagen

Also known as: Timogen, Thymogen, IM862, Oglufanide, EW dipeptide, Glu-Trp

Evidence: Clinical

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Overview

Synthetic dipeptide EW (Glu-Trp), registered in Russia as Timogen; tested in the US as IM862 (oglufanide), where a phase III trial in AIDS-related Kaposi sarcoma found no benefit over placebo.

Thymagen is the dipeptide Glu-Trp, the active substance of Timogen, a drug registered in Russia (ЛП-№(001808)-(РГ-RU), 13 February 2023) as a 100 mcg/1 mL intramuscular injection, a 25 mcg per dose nasal spray and a 0.05% cream. The same molecule was developed in the US as IM862, later named oglufanide, an angiogenesis inhibitor. A randomized study in AIDS-related Kaposi sarcoma (n=44) was followed by a phase III trial (n=202) in which it was not superior to placebo (Tulpule 2000; Noy 2005). Phase II work in renal cell carcinoma and prostate cancer also failed (Deplanque 2004; Mao 2007). In rats it slowed aging and inhibited spontaneous carcinogenesis (Anisimov 2000). Most Russian work comes from the developing group.

Benefits

Registered drug in Russia (Timogen: injection, nasal spray, cream), AIDS-related Kaposi sarcoma: not superior to placebo (human phase III RCT, n=202), slower aging and fewer spontaneous tumours (rat), NK-cell-dependent antitumour activity (animal)

Dosing reference

Research dose: 200 to 1000 mcg daily: vendor/community range, 2 to 10 times the Russian label dose of 100 mcg IM
Range: 200 to 1000 mcg, 1x daily

Russian label (Timogen): 100 mcg in 1 mL by intramuscular injection, a 25 mcg per dose intranasal spray and a 0.05% cream. IM862 was given as a nasal solution in the US Kaposi sarcoma trials (Tulpule 2000). The catalog range of 200 to 1000 mcg daily is a community figure, 2 to 10 times the label injection dose.

Mechanism

Proposed, from mixed sources. Under the name IM862 it was developed as an angiogenesis inhibitor (Noy 2005). Its antitumour activity in vivo required natural killer cell cytolytic activity (Smith 2003). The developer group reports that EW, as a component of Thymalin, alters genes and proteins involved in COVID-19 pathogenesis (Linkova 2023). The Russian label states the dipeptide is cleaved to glutamic acid and tryptophan. The old claims about thymocyte selection and T-cell export had no source.

Evidence

Clinical: at least one published human trial or an approved drug

Randomized study of IM862 nasal solution in AIDS-related Kaposi sarcoma, n=44 (Tulpule et al., 2000)
Slowed aging and inhibited spontaneous carcinogenesis in rats (Anisimov et al., 2000)
Antitumour activity in vivo depended on natural killer cell cytolytic activity (Smith et al., 2003)
In human peripheral blood lymphocyte culture, a chromosome aberration study found high concentrations reduced lymphocyte proliferation (Rushkovskii et al., 1996)
Phase II trials: no responses in metastatic renal cell carcinoma (Deplanque et al., 2004); failed as a candidate in an intermittent androgen ablation prostate cancer screen (Mao et al., 2007)
Human-trial status: registered in Russia as Timogen. As IM862 it was not superior to placebo in a phase III RCT in AIDS-related Kaposi sarcoma (n=202; response rate 23% with IM862 vs 21% with placebo) and time to progression was shorter on IM862 (16 vs 35 weeks) (Noy et al., 2005)

References

Side effects

In human lymphocyte culture, high concentrations reduced proliferation, measured in a chromosome aberration study (Rushkovskii 1996). No adverse-event summary from the IM862 trials or the Russian label is included yet. Commonly reported (anecdotal): injection-site irritation.

Storage

Storage: Room temperature
Lyophilized: 24+ months

Pharmacology

Half-life: No published half-life found. The Russian label states the dipeptide is cleaved to glutamic acid and tryptophan
Bioavailability: Not reported in the sources reviewed. Registered routes in Russia are intramuscular, intranasal and topical; IM862 was given as a nasal solution in US trials (Tulpule 2000)
Molecular weight: 333.34 Da
Sequence: Glu-Trp