Calpain inhibitor XII

A protease inhibitor.

Phase of research

Potential treatment - pre-clinical evidence

How it helps


Drug status

Used to treat other disease

Supporting references
Contradictory references
AI-suggested references
Clinical trials

General information

Calpain inhibitor XII is a reversible protease inhibitor active selectively against calpain I (with lower affinity also against calpain II and cathepsin B) (Cayman chemical). It was also shown to inhibit SARS-CoV-2 3C-like protease in vitro (Ma et al., 2020) and thus likely acts dually (combined with cathepsin L inhibition) against SARS-CoV-2 infection (Hu et al., 2021).

Calpain inhibitor XII on PubChem


Structure image - Calpain inhibitor XII


Supporting references

Link Tested on Impact factor Notes Publication date
Boceprevir, GC-376, and calpain inhibitors II, XII inhibit SARS-CoV-2 viral replication by targeting the viral main protease
3CLpro Crystallization Small molecule Enzyme assay In vitro
in vitro enzyme assay; crystallization; Vero 76 cells; SARS-CoV-2 strain USA-WA1/2020 20.51

Inhibited SARS-CoV-2 3C-like protease with an IC50 of ca. 0.45 μM in vitro.

Inhibited SARS-CoV-2 infection in primary CPE assay with an EC50 of ca. 0.49 μM and an SI of >204.

Evaluation of SARS-CoV-2 3C-like protease inhibitors using self-assembled monolayer desorption ionization mass spectrometry
3CLpro Small molecule Enzyme assay In vitro
in vitro enzyme assay; Vero E6 cells; MRC-5 human lung fibrobrast cells; HeLa cells 4.10

Manifests inhibitory activity (weaker than GC376) on the SARS-CoV-2 3C-like protease at non-cytotoxic concentrations.

Development of a Cell-Based Luciferase Complementation Assay for Identification of SARS-CoV-2 3CLpro Inhibitors
3CLpro Small molecule Enzyme assay In vitro
in vitro enzyme assay 3.82

The compound inhibited the SARS-CoV-2 3C-like protease in vitro with maximum inhibition of 26% relative to the inhibition by 100 μM GC376 and it showed CC50 of >100 μM.

Dual inhibition of SARS-CoV-2 and human rhinovirus with protease inhibitors in clinical development
3CLpro Cathepsin L Small molecule Enzyme assay In vitro
in vitro enzyme assay 4.10

The compound inhibited the SARS-CoV-2 3C-like protease with IC50 of 383 nM and human cathepsin L with IC50 of 0.69 nM in vitro.

Boceprevir, Calpain Inhibitors II and XII, and GC-376 Have Broad-Spectrum Antiviral Activity against Coronaviruses
Biophysical assay Cathepsin L Enzyme assay In vitro Mechanism
in vitro enzyme assay; in vitro biophysical assay; Vero cells; Caco-2 cells; (HIV-1) SARS-CoV-2 Spike pseudovirus 4.61

The compound inhibited cathepsin L in vitro with an IC50 of 1.63 nM. It neutralized SARS-CoV-2 pseudovirus in vitro with IC50s of ca. 6.62 μM and ca. 1.92 μM, alone or in the presence of 2 μM CP-100356 (an efflux pump inhibitor), respectively. The compound also inhibited SARS-CoV-2 replication in Caco-2 cells with an EC50 of ca. 4.21 μM and low cytotoxicity (CC50 >100 μM).


AI-suggested references