Protease and Enzyme Inhibitors
23 compounds in this family, each with its recorded mechanism, routes of administration, safety notes and references to published literature.
- acetylleucyl-leucyl-norleucinalAcetylleucyl‑leucyl‑norleucinal (ALLN) is a synthetic peptide‑based inhibitor of the proteasome and related cysteinyl proteases. In research settings it is employed to block proteolytic degradation of proteins such as apolipoprotein B, thereby influencing very‑low‑density lipoprotein (VLDL) assembly in hepatic cells.
- Alpha-1-proteinase inhibitorAlpha-1-proteinase inhibitor (A1PI), also called alpha‑1 antitrypsin, is a serpin‑type protein used as a prescription drug delivered by intravenous infusion. It is approved for augmentation therapy in patients with hereditary alpha‑1 antitrypsin deficiency who develop lung disease, aiming to restore the balance between neutrophil elastase and its inhibitor and to slow emphysema progression.
- AntipainAntipain is a small peptide originally isolated from microorganisms that belongs to the protease‑inhibitor family. It is employed primarily as a research tool to block protease activity in biochemical and cellular assays, and its inhibitory profile has sparked interest in possible analgesic mechanisms. Antipain has not been approved for any therapeutic indication and remains confined to laboratory investigations.
- Antithrombin III humanHuman antithrombin III (AT‑III) is a plasma‑derived serine protease inhibitor used as a prescription product to replace deficient AT‑III levels. It is administered intravenously or subcutaneously to patients with hereditary AT‑III deficiency or to reduce thrombotic risk during high‑risk situations such as surgery, childbirth, or severe trauma. The preparation is a purified protein derived from donor plasma and is listed among the most costly blood‑product drugs in intensive‑care settings.
- ArgadinArgadin is a naturally‑derived cyclic pentapeptide that inhibits family‑18 chitinases. Discovered in soil‑derived microorganisms, it binds with nanomolar affinity to bacterial chitinase B and also blocks human and fungal chitinases in vitro. Researchers use Argadin as a molecular probe of chitinase function and as a lead scaffold for developing antifungal, insecticidal, or anti‑inflammatory agents.
- AtazanavirAtazanavir is an azapeptide protease inhibitor developed for the treatment of human immunodeficiency virus type‑1 (HIV‑1) infection. It is administered orally once daily and works by inhibiting the viral protease required for maturation of infectious virions. Clinical studies have shown it reduces viral load in treatment‑naïve patients and is approved by the U.S. Food and Drug Administration for use in combination antiretroviral regimens.
- CA-074 methyl esterCA-074 methyl ester (CA‑074Me) is a research‑grade small‑molecule inhibitor of the cysteine protease cathepsin B. It is employed in cell‑culture and animal studies to probe the role of cathepsin B in processes such as ferroptosis, inflammasome activation, viral entry, and neurodegeneration. The compound is not an approved drug and is used experimentally via injection, oral dosing, or in‑vitro exposure.
- CarfilzomibCarfilzomib is an intravenously administered, epoxyketone‑based proteasome inhibitor approved for use in multiple myeloma. It is combined with dexamethasone, and often with other agents such as isatuximab or lenalidomide, to treat relapsed or refractory disease. Pre‑clinical work also suggests it can enhance novel KRAS‑G12D inhibitors, and it shows activity in Waldenström macroglobulinemia in later‑line settings.
- ChymostatinChymostatin is a research‑grade peptide aldehyde that inhibits serine proteases such as chymase, cathepsin G, and other chymostatin‑sensitive enzymes. It is employed chiefly to study alternative, ACE‑independent pathways of angiotensin‑II formation and to protect therapeutic peptides from enzymatic degradation in vitro.
- ElafinElafin is a human serine protease inhibitor belonging to the whey‑acidic‑protein (WAP) family. It is produced by epithelial cells and naturally limits neutrophil elastase and proteinase‑3 activity while displaying antimicrobial properties. Research is exploring its use as a therapeutic agent for inflammatory lung disease, intestinal disorders, vascular injury, and postoperative inflammation, as well as a potential antimicrobial against resistant bacteria.
- Human C1-esterase inhibitorHuman C1‑esterase inhibitor (C1‑INH) is a plasma‑derived or recombinant serpin used to treat hereditary angioedema (HAE), a rare disorder causing recurrent swelling of the skin, gastrointestinal tract, and airway. Approved formulations such as Berinert (plasma‑derived) and recombinant products are administered intravenously for on‑demand relief of acute attacks and, in some regimens, for short‑term prophylaxis.
- KelatorphanKelatorphan (also known as RB 38A) is a synthetic peptide‑like inhibitor of several zinc‑metallopeptidases that degrade endogenous enkephalins, chiefly neutral endopeptidase (NEP) and aminopeptidase N (APN). By blocking these enzymes it preserves enkephalins in the nervous system, producing analgesic effects in animal models. It has also been reported to inhibit leukotriene A4 hydrolase, suggesting possible anti‑inflammatory activity. Kelatorphan is used only in research settings and has not been approved for clinical use.
- LancovutideLancovutide (also known as duramycin, Moli1901) is an investigational peptide being studied for cystic fibrosis. Delivered by inhalation, it is intended to increase airway surface liquid by activating a calcium‑dependent chloride channel, thereby promoting mucus hydration and clearance.
- LeupeptinLeupeptin is a peptide aldehyde that inhibits a range of serine and cysteine proteases. In research it is employed to block proteolytic degradation of biomolecules, to probe protease‑dependent activation pathways, and to improve the stability of peptide drugs such as insulin in experimental formulations.
- MotuporinMotuporin is a cyclic pentapeptide originally isolated from cyanobacteria and marine sponges. It acts as a potent inhibitor of protein phosphatases PP1 and PP2A, enzymes that remove phosphate groups from serine/threonine residues. The compound is used experimentally to probe phosphatase function and as a scaffold for designing selective inhibitors. Because the inhibition is rapid and reversible, motuporin serves as a valuable chemical probe for dissecting signaling pathways that depend on PP1/PP2A activity.
- NerinetideNerinetide (also known as NA-1, PSD‑95 inhibitor peptide, Tat‑NR2B9c) is an investigational neuroprotective peptide designed to limit neuronal injury during acute ischaemic stroke. It is administered intravenously as a single dose in conjunction with reperfusion therapies such as mechanical thrombectomy. Clinical trials have evaluated its safety and efficacy, but definitive benefit on functional outcomes has not been demonstrated.
- OprozomibOprozomib (ONX‑0912, PR‑047) is an orally bioavailable, irreversible epoxyketone proteasome inhibitor under clinical investigation for the treatment of multiple myeloma and other cancers. As a second‑generation analogue of carfilzomib, it targets the 20S proteasome core, leading to accumulation of ubiquitinated proteins and tumor cell death. Preclinical work highlights anti‑angiogenic activity and synergistic anti‑myeloma effects when combined with dexamethasone and pomalidomide.
- PepstatinPepstatin (also called pepstatin A) is a small peptide inhibitor of aspartyl proteases that is employed primarily as a research tool. It binds to the active sites of enzymes such as cathepsin D and the presenilinase component of the γ‑secretase complex, allowing scientists to probe lysosomal protein turnover, enzyme purification, and amyloid‑precursor processing. The compound is not approved for therapeutic use and is investigated through in‑vitro and animal‑model studies.
- Recombinant Alpha-1-antitrypsinRecombinant alpha‑1‑antitrypsin (rAAT) is a laboratory‑produced version of the serpin protein that normally inhibits neutrophil elastase. It is being investigated as a replacement therapy for individuals with alpha‑1‑antitrypsin deficiency, a genetic condition that predisposes to emphysema, bronchiectasis, and, in some studies, cystic fibrosis‑related lung damage. Current research explores intravenous infusion of an AAT‑Fc fusion (INBRX‑101) and inhaled delivery, including a novel dry‑powder formulation, as alternatives to plasma‑derived AAT infusions.
- Reversin 121Reversin 121 (also called P‑gp inhibitor peptide 121) is a short, high‑affinity peptide that blocks the activity of the ATP‑binding cassette transporter P‑glycoprotein (P‑gp, MDR1). It is investigated as a research‑grade chemosensitizer intended to reverse multidrug resistance (MDR) in cancer cells, thereby improving the efficacy of conventional chemotherapeutics such as doxorubicin. Pre‑clinical work also shows tumor‑growth reduction in mouse pancreatic cancer models and potentiation of proteasome‑inhibitor activity in resistant blood cells.
- TalabostatTalabostat (also known as PT‑100, Val‑boroPro) is an investigational oral small‑molecule inhibitor of dipeptidyl peptidases (DPP4, DPP8/9). It is being explored primarily as an immunomodulatory agent to boost anti‑cancer immunity, often in combination with checkpoint‑inhibitor antibodies such as pembrolizumab.
- TelaprevirTelaprevir (brand names Incivek, Incivo) is an oral, prescription peptidomimetic inhibitor of the hepatitis C virus (HCV) NS3/4A protease. Approved in 2011 for genotype 1 infection, it was used together with pegylated interferon and ribavirin to raise cure rates. By 2013 it was withdrawn from the market as newer, more effective, interferon‑free regimens replaced it.
- Z-Pro-ProlinalZ‑Pro‑Prolinal (ZPP) is a synthetic dipeptide aldehyde that acts as a potent inhibitor of prolyl oligopeptidase (POP), an enzyme that cleaves proline‑containing oligopeptides. In pre‑clinical research it has been used to probe POP function, to assess neuroprotective effects, and to explore antiparasitic activity against Trypanosoma evansi. The compound is not approved for clinical use and is employed only in laboratory settings via intracerebroventricular, intraperitoneal, or intravenous administration.