protease-resistant

TCS PrP Inhibitor 13 (5-(4-Nitrophenyl)-2-Phenyl-4H-Pyrazol-3-One) is an antiprion agent inhibiting protease-resistant prion protein (PrP-res) accumulation.

Grazoprevir sodium salt is a selective Hepatitis C virus NS3/4a protease inhibitor with broad activity across genotypes and resistant variants.

Azvudine (FNC) is a potent nucleoside reverse transcriptase inhibitor (NRTI), with antiviral activity on HIV, HBV and HCV. Azvudine inhibits NRTI-resistant viral strains. Azvudine exerts highly potent inhibition on HIV-1 (EC50s ranging from 0.03 to 6.92 nM) and HIV-2 (EC50s ranging from 0.018 to 0.025 nM).

HP211206 is a PROTAC degrader of the SARS-CoV-2 main protease (Mpro). It effectively degrades both the SARS-CoV-2 Mpro and its resistant mutants. The IC50 for HP211206 against Mpro is 181.9 nM, and the DC50 is 621 nM. HP211206 also exhibits antiviral activity.

USP1-IN-11 (compound 38-P2) is a selective, reversible, and non-competitive inhibitor of USP1 (Ubiquitin-specific protease 1). It activates the DDR (DNA damage repair) pathway, leading to cell cycle arrest and apoptosis, thereby inhibiting cell survival. USP1-IN-11 increases sensitivity to Olaparib in drug-resistant cells and works synergistically with Andrographolide in cancer cells with functional BRCA. In the MDA-MB-436 xenograft model, USP1-IN-11 demonstrates significant dose-dependent antitumor activity.

Jun13296 is an orally active quinoline SARS-CoV-2 papain-like protease inhibitor (IC50 = 0.13 µM, Ki = 8.8 nM). It demonstrates potent inhibitory effects against SARS-CoV-2 variants and Nirmatrelvir-resistant mutants. Jun13296 reduces lung viral titers and prevents lung tissue damage in SARS-CoV-2 infection models.

USP1-IN-11 (compound 38-P2) is a selective, reversible, and non-competitive inhibitor of USP1 (Ubiquitin-specific protease 1). It promotes the activation of the DDR (DNA damage repair) pathway, inducing cell cycle arrest and apoptosis, thereby inhibiting cell viability. USP1-IN-11 increases the sensitivity of cells resistant to Olaparib and shows synergistic effects with Andrographolide in cancer cells with normal BRCA function. In the MDA-MB-436 xenograft model, USP1-IN-11 exhibits a significant dose-dependent antitumor effect.

AB-343 is a selective covalent inhibitor of SARS-CoV-2 Mpro with an IC50 of 8 nM and a Ki of 2.8 nM. It effectively inhibits the main protease of SARS-CoV-2 and several other coronaviruses and is active against some resistant variants. AB-343 can be utilized in research related to diseases associated with coronavirus infections.

THX6 is an activator of human mitochondrial protease ClpP, with an EC50 of 1.18 μM. It displays cytotoxicity in ONC201-resistant SU-DIPG-VI cells, with an IC50 of 0.13 μM. THX6 inhibits the expression of mitochondria-related proteins (such as parkin, TFAM, NRF1, SDHA), leading to impaired mitochondrial function. Additionally, THX6 affects cell membrane lipid metabolism and exhibits antitumor potential.

Mer-NF5003F (Stachybotrydial; F 1839M) is a sesquiterpene isolated from Stachybotrys, effective in inhibiting avian myeloblastosis virus (AMV) protease with an IC50 of 7.8 μM. It also inhibits sialyltransferases ST6N, ST3O, and ST3N with IC50 values of 0.61, 6.7, and 10 μg/mL, respectively, and fucosyltransferase with an IC50 of 11.3 μg/mL. Additionally, Mer-NF5003F exhibits in vitro activity against herpes simplex virus HSV-1 (IC50=4.32 μg/mL) and multi-drug-resistant Plasmodium falciparum K1 strain (IC50=0.85 μg/mL).

HIV-1protease-IN-13 (compound 18d) is a potent inhibitor of HIV-1 protease (HIV-1protease) with an IC50 value of 0.54 nM. Additionally, HIV-1protease-IN-13 demonstrates effective activity against both HIV-1DRVRS (DRV resistant mutation) and HIV-1NL4_3 variants (wild-type).

MPD2 is a PROTAC compound based on a Cereblon-binding ligand that degrades the main protease MPro of SARS-CoV-2. In 293T cells, it effectively reduces MPro protein levels with a DC50 of 296 nM and shows time-dependent activity. MPD2 exhibits strong antiviral properties against various SARS-CoV-2 strains and has increased potency against Nirmatrelvir-resistant variants. It holds potential for researching SARS-CoV-2 diseases.

Anti-MRSA agent 32 (Compound 26) is an orally active selective activator of the Staphylococcus aureus ClpP protease (SaClpP) with an EC50 of 0.98 μM. By activating the SaClpP protease, it causes the abnormal degradation of bacterial proteins and inhibits the proliferation of Staphylococcus aureus. In a mouse skin infection model, Anti-MRSA agent 32 promotes wound healing. This compound holds potential for research in methicillin-resistant Staphylococcus aureus (MRSA) and other infectious diseases.

ZY39 is a selective casein protease P (ClpP) agonist that inhibits the growth of multidrug-resistant strains by selectively activating Staphylococcus aureus ClpP (SaClpP). ZY39 also promotes the enzymatic hydrolysis of human ClpP (HsClpP) in vitro. ZY39 inhibits the growth of multidrug-resistant strains in a mouse peritonitis model of Staphylococcus aureus infection. ZY39 can be used in research related to Staphylococcus aureus infections.

Grazoprevir, a second generation hepatitis C virus protease inhibitor acting at the NS3/4a protease targets, has good activity against a range of hepatitis C virus genotype variants, including some that are resistant to most currently used antiviral medic

GRL-142 is a potent HIV-1 protease inhibitor capable of crossing the blood-brain barrier. It exhibits exceptional inhibitory activity against both wild-type and multi-drug resistant strains (IC50=0.0094 nM). GRL-142 employs a unique scaffold-binding mechanism, synergistically engaging with the P2/P2' segments through fluorine-mediated stable interactions to maintain its bioactive conformation. It adapts to p51HIV-1 protease mutants by directly interacting with flap-tip residues to maintain flap-closed states. Furthermore, GRL-142 disrupts the flap-water hydrogen bond network in wild-type protease, effectively blocking viral replication. This compound is applicable to studies of HIV-1 infection and associated neurocognitive disorders (HAND).

AG-7404 is a potent protease inhibitor with anti-poliovirus activity. AG-7404 was active against all virus with EC50 values ranging from 0.080 to 0.674 μM. AG-7404 was fully active against V-073-resistant variants with EC50 values ranging from 0.218 to 0.

SM111 inhibits in vitro replication of HIV-1, including strains resistant to reverse transcriptase, licensed protease, and integrase inhibitors, without major cellular toxicity.

CI-1029 is an HIV protease inhibitor that is effective against mutant HIV proteases and drug-resistant HIV strains. It has excellent protease activity, good antiviral efficacy in cell tests, and has good bioavailability in a variety of animal species.

Rab8a GTPase-binding stapled peptide (Kd = 12.7 μM). Cell permeable; localizes to the endomembrane system. Cromm et al (2016) Protease-resistant and cell-permeable double-stapled peptides targeting the Rab8a GTPase. ACS Chem.Biol. 11 2375 PMID:27336832

Tipranavir is a protease inhibitor that inhibits HIV-1 resistant to more than 1 protease inhibitor .Tipranavir effectively inhibits HIV-1 protease enzyme activity and dimerisation and has potent activity against multiple protease inhibitor (PI) HIV-1 isolates (IC50 of 66-410 nM). Tipranavir inhibits SARS-CoV-2 3CLpro activity.

HIV-1 protease-IN-6 (compound 17d) is a potent HIV-1 protease inhibitor with an IC50 of 21 pM and a Ki of 4.7 pM, demonstrating significant antiviral activity against DRV (darunavir) resistant mutants, surpassing its inhibition efficacy against wild-type viruses.

HIV-1 protease-IN-2 is a potent inhibitor of HIV-1 protease (IC50: 2.53 nM) and exhibits antiviral effects against DRV (Darunavir) sensitive and drug-resistant HIV-1 mutants.

HIV-1 protease-IN-5 is an HIV-1 protease inhibitor (IC50: 1.64 nM). HIV-1 protease-IN-5 exhibits significant effects on wild-type and DRV-resistant HIV-1.