MM3122
Source MM3122 at Peptiology
Save 10% with code PEPTI-BOSSRABBIT-10
Affiliate link: we earn a commission on purchases made through this link, at no extra cost to you.
Tapping Shop Now & Save 10% copies your 10% off code PEPTI-BOSSRABBIT-10 to your clipboard. Paste it at the Peptiology checkout to claim the discount.
Summary
MM3122 is a small‑molecule ketobenzothiazole inhibitor that targets host serine proteases such as TMPRSS2, matriptase and hepsin. By blocking these enzymes, it prevents activation of the coronavirus spike protein, thereby inhibiting entry of SARS‑CoV‑2, its EG.5.1 subvariant, MERS‑CoV and related viruses into human lung cells. Pre‑clinical studies show potent antiviral activity in cell culture and protective effects in a mouse model of COVID‑19.
Mechanism of Action
MM3122 acts as a covalent inhibitor of the transmembrane serine protease TMPRSS2 and related proteases. TMPRSS2 normally cleaves the SARS‑CoV‑2 spike protein, a step required for fusion with the host cell membrane. By irreversibly binding to the active‑site serine of TMPRSS2 (and similarly to matriptase and hepsin), MM3122 blocks spike priming, preventing viral attachment, entry and subsequent replication in respiratory epithelial cells.
What the Research Shows
Structure‑based design identified MM3122 as a lead ketobenzothiazole compound with an IC50 of 340 pM against recombinant TMPRSS2. In Calu‑3 lung epithelial cells, it blocked entry of a VSV‑SARS‑CoV‑2 chimeric virus at 430 pM and reduced SARS‑CoV‑2‑induced cytopathic effects with an EC50 of 74 nM; it also inhibited MERS‑CoV entry at 870 pM. In vitro, the molecule showed sub‑nanomolar potency against TMPRSS2, matriptase and hepsin and retained activity against the EG.5.1 variant. In mice, intraperitoneal dosing before or after infection reduced weight loss, lung congestion, pathology and pro‑inflammatory cytokine release; prophylactic dosing also lowered lung viral titers. Pharmacokinetic profiling in mice revealed a plasma half‑life of 8.6 h and lung half‑life of 7.5 h, with no overt toxicity reported.
Reported Benefits
MM3122 demonstrates exceptionally high potency against TMPRSS2 and related proteases, translating into strong inhibition of multiple coronaviruses in cell culture. Its broad-spectrum activity includes emerging SARS‑CoV‑2 variants and MERS‑CoV. In vivo, the compound provides both prophylactic and therapeutic benefit in a mouse COVID‑19 model, reducing disease severity and inflammatory responses. Favorable metabolic stability and a multi‑hour half‑life in plasma and lung tissue support its potential as a drug candidate.
Limitations of the Evidence
All data are pre‑clinical; no human safety or efficacy studies have been reported. Efficacy has been demonstrated only in vitro and in a mouse model using intraperitoneal injection, a route not directly translatable to routine clinical use. Long‑term safety, optimal dosing, and pharmacodynamics in humans remain unknown. The studies focus on viral entry inhibition, so effectiveness against established infection in humans is not established.
Safety Considerations
Mouse studies describe MM3122 as having excellent metabolic stability and no apparent acute toxicity at doses that achieved antiviral effects. The reported half‑life suggests moderate systemic exposure. However, no detailed adverse‑event profile, off‑target effects, or toxicology data in higher species are provided, so safety in humans cannot be inferred from the current literature.
How It Is Administered
In the published mouse experiments, MM3122 was administered by intraperitoneal injection, both before (prophylactic) and after (therapeutic) SARS‑CoV‑2 challenge. Formulation details are not disclosed in the abstracts. No oral, inhaled, or other delivery routes have been reported in the cited literature.
Routes of Administration
No administration routes recorded yet.
Goals & Uses
No goal associations recorded yet.
Contraindications
No contraindications recorded yet.
Adverse Effects
No adverse effects recorded yet.
Drug Interactions
No drug interactions recorded yet.
Population Constraints
No population constraints recorded yet.
Regulatory Status
No regulatory status recorded yet.
Evidence & Sources
- Journal ArticleLowMahoney M, et al.2021-01-01T00:00:00.000000Z
- Journal ArticleLowBoon ACM, et al.2024-01-01T00:00:00.000000Z
- Journal ArticleLowBoon ACM, et al.2024-01-01T00:00:00.000000Z
- Journal ArticleLowMahoney M, et al.2021-01-01T00:00:00.000000Z
Frequently Asked Questions
What type of compound is MM3122?
MM3122 is a synthetic small‑molecule ketobenzothiazole that covalently inhibits host serine proteases, especially TMPRSS2, which are required for coronavirus spike protein activation.
Has MM3122 been tested in humans?
No. All published data are limited to cell‑culture assays and mouse models; there are no clinical trial results or regulatory approvals reported for MM3122.
How does MM3122 differ from existing TMPRSS2 inhibitors like camostat?
MM3122 shows sub‑nanomolar potency (IC50 ≈ 340 pM) and superior antiviral activity in vitro compared with camostat and nafamostat, which have micromolar potency. It also exhibits favorable pharmacokinetics in mice.
Can MM3122 be used to treat COVID‑19 infections?
Pre‑clinical evidence suggests MM3122 can reduce disease severity and viral replication in mice when given before or shortly after infection, but without human data its therapeutic use in patients remains unproven.
What are the known safety concerns for MM3122?
Mouse studies reported no obvious acute toxicity at effective doses, but comprehensive safety, toxicology, and off‑target assessments have not been published, so potential adverse effects in humans are unknown.
What is MM3122?
MM3122 is a small‑molecule ketobenzothiazole inhibitor that targets host serine proteases such as TMPRSS2, matriptase and hepsin. By blocking these enzymes, it prevents activation of the coronavirus spike protein, thereby inhibiting entry of SARS‑CoV‑2, its EG.5.1 subvariant, MERS‑CoV and related viruses into human lung cells. Pre‑clinical studies show potent antiviral activity in cell culture and protective effects in a mouse model of COVID‑19.