PF-00835231
A protease inhibitor.
General information
PF-00835231 is a ketone-based cysteine protease covalent inhibitor designed to inhibit SARS-CoV 3C-like protease. It is the active metabolite of PF-07304814, its phosphate prodrug. It was shown to inhibit SARS-CoV-2 in a human adenocarcinoma alveolar epithelial cell line (de Vries et al., 2021). It manifests some human cathepsin L inhibition in vitro, as well (Liu et al., 2021).
PF-00835231 on PubChem
Synonyms
N-[(2S)-1-[[(2S)-4-Hydroxy-3-oxo-1-[(3S)-2-oxopyrrolidin-3-yl]butan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]-4-methoxy-1H-indole-2-carboxamide; Compound 4
CC(C)C[C@@H](C(=O)N[C@@H](C[C@@H]1CCNC1=O)C(=O)CO)NC(=O)C2=CC3=C(N2)C=CC=C3OC
Supporting references
| Link | Tested on | Impact factor | Notes | Publication date |
|---|---|---|---|---|
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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 5.7 nM and human cathepsin L with IC50 of 456 nM in vitro. The cathepsin L inhibition was relatively weak compared to some other inhibitors. |
Jan/27/2021 |
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A comparative analysis of SARS-CoV-2 antivirals characterizes 3CLpro inhibitor PF-00835231 as a potential new treatment for COVID-19
3CLpro Small molecule In vitro |
ACE2-expressing A549 cells; polarized human airway epithelia cultures; SARS-CoV-2 strain USA-WA1/2020; SARS-CoV-2 isolate USA/NYU-VC-003/2020 | 4.50 | The drug inhibited live SARS-CoV-2 isolates infection in a human epithelial cell line with sub-micromolar EC50s, which were similar or lower than those measured for remdesivir or GC-376 in parallel experiments. The experimental results suggest that it is active at the early stages of intracellular virus propagation. The drug was well tolerated in polarized human airway epithelia cells (HAECs), where it inhibited SARS-CoV-2 infection in a dose-dependent manner, with viral titres below detection limit at 10 μM. Its activity in human epithelial cells was not increased upon chemical blockage of MDR1 transporter (“P-glycoprotein”), indicating that PF-00835231’s intracellular levels in these cells are not decreased by MRD1. Moreover, MDR1 transcripts were not detectable in HAECs. |
Feb/23/2021 |
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Is PF-00835231 a Pan-SARS-CoV-2 Mpro Inhibitor? A Comparative Study
3CLpro Small molecule In silico |
in silico | 3.27 | Predicted to inhibit SARS-CoV-2 3C-like protease and some of its mutant variants. |
Mar/17/2021 |
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Discovery of Ketone-Based Covalent Inhibitors of Coronavirus 3CL Proteases for the Potential Therapeutic Treatment of COVID-19
3CLpro Crystallization Small molecule Enzyme assay In vitro |
In vitro | 7.45 | The compound potently inhibits SARS-CoV-2 3C-like protease with a Ki of ca. 0.27 nM in vitro. The compound binds to the enzyme’s active site. |
Oct/15/2020 |
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Efficacy of Antibodies and Antiviral Drugs against Covid-19 Omicron Variant
Spike protein Spike variant Protein factor In vitro Antibody |
Vero E6-TMPRSS2 cells; SARS-CoV-2 strains (SARS-CoV-2/UT-NC002-1T/Human/2020/Tokyo, alpha, beta, gamma, delta, omicron) | 91.25 | The drug retained its anti-SARS-CoV-2 activity against all of the strains tested (WT-like, alpha, beta, gamma, delta, omicron). |
Jan/26/2022 |
