Proteases/Proteasome

<p>Yimitasvir diphosphate, also known as Emitasvir, is an orally-administered inhibitor of the hepatitis C virus (HCV) nonstructural protein 5A (NS5A).</p>

<p>Tyropeptin A-4 is used as a proteasome inhibitor.</p>

<p>BMS-189664 is an inhibitor of thrombin.</p>

<p>HCV-IN-44 (compound 28) is an inhibitor of the HCV NS5B protein, efficacious in suppressing HCV virus replication and useful for researching HCV infection [1].</p>

<p>HCV-IN-43 (compound 2), an HCV NS5B protein inhibitor, efficiently inhibits HCV virus replication and is utilized in the study of HCV infection [1].</p>

<p>Reverse transcriptase-IN-1 is a diarylbenzopyrimidine (DABP) analogue and a potent inhibitor of HIV-1 nonnucleoside reverse transcriptase with an IC50of 13.7</p>

<p>Cathepsin K inhibitor 3: Selective, IC50 of 0.5 nM, good pharmacokinetics, potential for OA research.</p>

<p>Mergetpa, a carboxypeptidase inhibitor, impedes the conversion of kinins and B2 receptor antagonists into metabolites devoid of the C-terminal arginine [1].</p>

<p>Cathepsin Inhibitor 2 is a potent Cathepsin S inhibitor (Ki: &lt;20 nM).</p>

<p>LY52 is a matrix metalloproteinase-2 inhibitor. It acts by suppressing tumor invasion and metastasis.</p>

<p>Atecegatran Metoxil (AZD0837), an oral thrombin inhibitor in development for stroke prevention in atrial fibrillation, is well-tolerated with favorable PK.</p>

<p>HIV-1 protease-IN-11 (compound 34a), an HIV-1 protease inhibitor, demonstrates potent inhibition with an IC50 of 0.41 nM and maintains substantial efficacy</p>

<p>Matrix metalloproteinase-3 (MMP-3), also known as stromelysin-1, is a critical enzyme involved in tissue remodeling and repair through its role in degrading extracellular matrix proteins, facilitating cell migration. This enzyme has been implicated in various physiological processes including vascular remodeling associated with aneurysm formation, wound healing, the progression of atherosclerosis, and tumor initiation. MMP-3 inhibitor VIII, a cell-permeable sulfonamide-based hydroxamic acid, effectively inhibits MMP-3 by binding to its active site (Ki = 23 nM), thus blocking its enzymatic activity. Additionally, this inhibitor has been demonstrated to suppress the activity of mouse macrophage metalloelastase MME/MMP-12, with an IC50 value of 13 nM, highlighting its potential utility in research on tissue remodeling and disease processes involving MMPs.</p>

<p>Dim16, a dual inhibitor of PCSK9/HMG-CoAR, demonstrates potent activity with an IC50 of 19 nM against PCSK9 and significantly impedes PCSK9-LDLR interaction</p>

<p>DS-1040 Tosylate is a thrombin-activated fibrinolysis inhibitor (TAFI) inhibitor and a fibrinolysis enhancer, used for researching thromboembolic diseases.</p>

<p>M867 is a selective, reversible caspase-3 inhibitor, possessing an IC50 of 1.4 nM and a Ki value of 0.7 nM, demonstrating anti-apoptotic activity [1].</p>

<p>LM-030, also known as BPR277, is a novel inhibitor of kallikrein-related peptidase 7 (KLK7) and epidermal elastase 2 (ELA2).</p>

<p>MMP-9 inhibitor I is an inhibitor of matrix metalloproteinase-9 (MMP-9) that is selective over MMP-1 and MMP-13 (IC50s = 5, 1,050, and 113 nM, respectively).</p>

<p>M109S is a novel small molecule that shields cells from mitochondria-dependent apoptosis, demonstrating effectiveness both in vitro and in vivo.</p>

<p>NS5A-IN-3 is a potent NS5A inhibitor with high efficacy against HCV 1b, good activity on 3a, and strong metabolic stability; superior to daclatasvir.</p>

<p>PNU-103017 is an inhibitor of HIV protease.</p>

<p>L-689502 is a potent HIV-l protease inhibitor (IC50: 1 nM).</p>

<p>GSK-625433: Homochiral inhibitor blocks HCV genotypes 1a/1b polymerase.</p>

<p>Petesicatib is an inhibitor of cathepsin S. Petesicatib used in the research of immune diseases.</p>

<p>SID 26681509 is a selective, reversible and competitive human cathepsin L inhibitor (IC50 of 56 nM).</p>

<p>MMP3 inhibitor 1 is a potent and highly selective inhibitor of MMP-3 (IC50 of 1 nM).</p>

<p>FK706, a human neutrophil elastase inhibitor (IC50: 83 nM, Ki: 4.2 nM), also blocks mouse and porcine elastases. Anti-inflammatory.</p>

<p>PDDC inhibitor (Phenyl (R)-(1-(3-(3,4-dimethoxyphenyl)-2,6-dimethylimidazo[1,2-b]pyridazin-8-yl)pyrrolidin-3-yl)carbamate) is an nSMase2 inhibitor.</p>

<p>Filibuvir (PF-00868554) inhibits HCV polymerase genotypes 1a/1b, EC50s 59 nM.</p>

<p>Ac-YVAD-AOM is a selective and potent caspase-1 inhibitor showing antitumor activity and potential analgesic activity.</p>

<p>Collagen proline hydroxylase inhibitor-1 具有抗纤维增生活性。</p>

<p>ZED-1227 (TAK-227) is a TG2 inhibitor with anticancer activity that blocks inflammation-induced TG2 expression and activation for the treatment of Celiac Diseas</p>

<p>gamma-Glu-Tyr (gamma-Glutamyltyrosine) is a kokumi peptide against dipeptidyl peptidase-IV (DPP-IV) and is used in the study of diabetes mellitus.</p>

<p>HIV-1 inhibitor-54: potent anti-HIV (EC50: 32 nM), targets WT HIV-1 IIIB in MT-4 cells for infection research.</p>

<p>Aderamastat (FP-025) is an orally active matrix metalloproteinase 12 (MMP-12) inhibitor indicated for the study of allergic asthma, COPD and pulmonary fibrosis.</p>

<p>Nesbuvir: HCV NS5B polymerase inhibitor, IC50 9 nM against HCV 1b replicon in liver cancer cells.</p>

<p>BMS-212122 inhibits MTP, reduces lipids and plaque in animal tests.</p>

<p>MK-0674 is a cathepsin K inhibitor (IC50: 0.4 nM) that inhibits Cat B, Cat F, Cat L, and Cat S for metabolism-related diseases.</p>

<p>VBY-825 is a reversible inhibitor of cathepsin with high potency against cathepsins B, L, S and V.</p>

<p>HCVNS5B polymerase-IN-2 (Compound 298) is an inhibitor of the Ns5b polymerase. It holds potential for research into the treatment of hepatitis C virus (HCV) infections.</p>

<p>(2R,3S)-Emricasan ((2R,3S)-PF 03491390) is an isomer of Emricasan. This compound acts as an orally effective irreversible pan-caspase inhibitor. (2R,3S)-Emricasan inhibits the increase in caspase-3 activity induced by Zika virus (ZIKV) and protects human cortical neural progenitor cells.</p>

<p>Beclabuvir blocks HCV NS5B polymerase at thumb site 1, effective on genotypes 1, 3, 4, 5 with IC50 &lt;28 nM.</p>

<p>Immunoproteasome Activator 1 (compound A) is a selective immunoproteasome activator that enhances the presentation of individual MHC-I binding peptides by over 100 times. It binds to the proteasomal structural subunit PSMA1 and facilitates the association of the proteasome activators PA28α/β (PSME1/PSME2) with the immunoproteasome.</p>

<p>UK-370106 is a potent and highly selective inhibitor of MMP-3 with IC50 of 23 nM and MMP-12 with IC50 of 42 nM, and potently inhibits cleavage of [3H]-</p>

<p>Isobutylamido thiazolyl resorcinol is a tyrosinase (Tyrosinase) inhibitor that prevents pigment deposition induced by ultraviolet radiation.</p>

<p>LK-732 is a thrombin inhibitor with antithrombotic activity. It exhibits dose-dependent inhibition in models of hypercoagulability, with an IC50 value of 1.3 mg/kg. LK-732 is used in cardiovascular and cerebrovascular research.</p>

<p>Boc 3 Arg is a tert-butyl carbamate-protected arginine compound. It serves as an efficient tag that induces degradation by directly targeting proteins to the 20S proteasome.</p>

<p>3-Aminobenzene-1,2-diol (compound C8) is an inhibitor of matrix metalloproteinases (MMP), with IC50 values of 20, 26, 16, and 16.3 μM against MMP-2, MMP-8, MMP-9, and MMP-14, respectively.</p>

<p>TGase2-IN-1 (Compound 22) is an orally effective TGase2 inhibitor with an IC50 of 1.12 µM. It inhibits TGase2 in human retinal microvascular endothelial cells with a strikingly lower IC50 of 0.07 µM. The oral bioavailability of TGase2-IN-1 is 74.6%. Additionally, it can suppress retinal vascular leakage in a mouse model of diabetes induced by Streptozotocin.</p>

<p>Tyrosinase-IN-39 (compound 5r) is a competitive inhibitor of tyrosinase, with an IC50 of 6.4 μM, and is used in the study of skin diseases.</p>

<p>SCO-792: potent, reversible oral enteropeptidase inhibitor, with slow in vitro dissociation and in vivo protein digestion blocking.</p>

<p>PNU-248686A is an inhibitor of matrix metalloproteinase (MMP).</p>

<p>CM-352 is a metalloproteinase inhibitor that reduces brain damage and improves functional recovery in rat models of cerebral hemorrhage.</p>

<p>DPP-4-IN-15 (Compound 22) is a non-competitive inhibitor of dipeptidyl peptidase-4 (DPP-4) with an IC50 value of 8.24 μM.</p>

<p>UK 356618 is a potent and selective inhibitor of matrix metalloprotease-3 (IC50: 5.9 nM).</p>

<p>Verducatib is an inhibitor of cathepsins (cathepsin).</p>

<p>Anti-infective agent 10 (Compound Example 30) is an ns5b polymerase inhibitor that functions as an anti-HCV agent.</p>

<p>HCV-IN-39 is a potent oral drug inhibiting HCV, effective on GT1a (EC50: 0.259μM), GT1b (EC50: 0.434μM), GT1b CES1 (EC50: 0.069μM) replicons.</p>

<p>RBx-0597 is a selective DPP-IV inhibitor with IC50 values of 32 nM, 31 nM, and 39 nM for human, mouse, and rat plasma DPP-IV, respectively. It is utilized in research focused on type 2 diabetes.</p>

<p>GB111-NH2, a cysteine cathepsin inhibitor, is applicable in cancer research [1].</p>

<p>Marizomib is a novel irreversible brain-permeable proteasome inhibitor that inhibits CT-L, CT-T-laspase-like, and trypsin-like 20S proteasomes.Cost-effective and quality-assured.</p>

<p>GSK5852, an HCV NS5B inhibitor, has IC50 of 50 nM; potently fights HCV with EC50 of 3.0 nM for GT1a and 1.7 nM for GT1b.</p>

<p>Odiparcil is an orally active beta-d-thioxyloside analog.</p>

<p>BI-1942 is a chymase inhibitor with an IC50 value of 0.4 nM against human chymase. It is applicable for research in ophthalmic diseases.</p>

<p>ONO-6818 quarterhydrate: oral neutrophil elastase inhibitor, Ki 12.2 nM; &gt;100x less effective on other proteases; strong anti-inflammatory.</p>

<p>Plodicitinib is an inhibitor of Janus tyrosine kinase 3/TEC family kinase, exhibiting anti-inflammatory properties.</p>

<p>CatD-IN-1 (Compound 5) is a Cathepsin D inhibitor with an IC50 of 0.44 μM, and it shows potential for research in the field of osteoarthritis.</p>

<p>Matriptase-IN-2 free base, a matriptase inhibitor with a K i of 5 nM, has potential applications in musculoskeletal system disorder research (WO2011023958A1; compound 432) [1].</p>

<p>GLS-1-IN-1 (compound 1d) is a GLS-1 inhibitor that inhibits Hep G2, MCF 7 and MCF 10A cells.</p>

<p>Valopicitabine is an effective prodrug of the effective anti-HCV drug 2'-C-methylcytidine and can be used as a promising antiviral drug for the study of chronic</p>

<p>SSR-182289A (Free) is a thrombin inhibitor.</p>

<p>BMT-052 is a potent and selective Pan-genotypic HCV NS5B Polymerase Inhibitor (EC50 = 7 nM).</p>

<p>Tilpisertib fosmecarbil is a potent inhibitor of serine/threonine kinases with anti-inflammatory properties.</p>

<p>Monosodium 2-sulfoterephthalate (8) is an inhibitor of glutamate carboxypeptidase II.</p>

<p>Idraparinux Na is an Antithrombotic, Indirect, Selective, Synthetic Factor Xa Inhibitor</p>

<p>HCV-IN-7: potent oral HCV NS5A inhibitor, pan-genotypic, IC50s 3-47 pM, good pharmacokinetics, favorable liver uptake.</p>

<p>Tyrosinase-IN-37 (Compound 3c) is a potent inhibitor of tyrosinase, with an IC50 value of 1.02 μM, which is 14 times more effective than kojic acid (IC50 of 14.74 μM). This compound effectively prevents the browning of Rosa roxburghii and can also inhibit browning not caused by tyrosinase.</p>

<p>BI 224436 is an inhibitor of HIV-1 noncatalytic site integrase. With EC50 values of less than 15 nM against different HIV-1 laboratory strains.</p>

<p>ZINC09518833 is an α-ketoamide non-peptide proteasome inhibitor with an IC50 value of 12.4 μM. It can bind with both the active and inactive sites of the proteasome. ZINC09518833 shows promise for use in research related to multiple myeloma (MM).</p>

<p>Napsagatran hydrate is a novel and specific inhibitor of thrombin.</p>

<p>Dup-714 is a thrombin inhibitor.</p>

<p>Feniralstat (KVD-824) is a selective and potent kallikrein (kallikrein) inhibitor, useful in immune system diseases and cardiovascular disease research.</p>

<p>M826, a non-peptide, potent, selective, and reversible caspase-3 inhibitor, exhibits an IC50 of 0.005 μM and demonstrates strong anti-apoptotic activity in</p>

<p>Cathepsin K inhibitor 2 targets CTSK gene, may treat osteoporosis and osteoarthritis, detailed in patent WO2021147882A1.</p>

<p>(2S,4R)-Teneligliptin is a selective inhibitor of dipeptidyl peptidase IV (DPP-4). It increases the concentration of active glucagon-like peptide-1 (GLP-1) in plasma, which in turn stimulates insulin secretion when blood glucose levels are elevated, thereby exhibiting hypoglycemic effects. (2S,4R)-Teneligliptin is a promising candidate for research in type 2 diabetes.</p>

<p>Kallikrein-IN-1 (Formula A) is an inhibitor of the kinin-releasing enzyme Kallikrein.</p>

<p>TCL1 acts as a selective non-covalent inhibitor targeting the Pru domain of the Rpn-13 subunit within the 19S regulatory particle (19S RP) of the proteasome, with an IC50 value around 26 μM. It disrupts the recognition and transport of ubiquitinated proteins by Rpn-13, thus inhibiting proteasomal degradation and affecting intracellular protein metabolism balance. TCL1 holds potential for research in hematologic malignancies.</p>

<p>Cathepsin C-IN-5 (SF38) is a potent, oral Cathepsin C blocker with an IC50 of 59.9 nM; less active against Cat L/S/B/K; has anti-inflammatory effects.</p>

<p>GSK-2878175, a NS5B inhibitor, is used potentially for the treatment of HCV infection.</p>

<p>Piceid 6″-O-azelaic acid ester exhibited strong intracellular tyrosinase inhibition and decolorization activity.</p>

<p>ABT-072 is a nonnucleoside NS5B polymerase inhibitor and a candidate drug evaluated for treatment of hepatitis C virus.</p>

<p>Cyclophilin inhibitor 1: orally available, Kd 5 nM, potent against HCV, EC50 for HCV 2a is 98 nM.</p>

<p>Ciluprevir is a selective HCV NS3 protease inhibitor, effective against non-genotype-1 HCV; less potent for genotypes 2/3.</p>

<p>MK-8876 is an Inhibitor of HCV NS5B Site D.</p>

<p>GW-311616 is a long duration, orally bioavailable, and selective human neutrophil elastase (HNE) inhibitor (IC50: 22 nM; Ki: 0.31 nM).</p>

<p>MeO-Suc-Ala-Ala-Pro-Ala-CMK (MSACK) is an inhibitor of human neutrophil elastase (HNE) with an IC50 of 20.3 μM. It effectively inhibits the hydrolysis of substrates like lung tissue elastin by HNE and is applicable in studies related to conditions such as chronic obstructive pulmonary disease (COPD).</p>

<p>RIPK1-IN-26 is a potent inhibitor of Receptor-Interacting Serine/Threonine Kinase 1 (RIPK1), exhibiting anti-necrotic properties in cells. This compound demonstrates good metabolic stability and binding specificity in mice. RIPK1-IN-26 holds potential for development as a PET imaging probe and in the research of neurodegenerative diseases.</p>

<p>Freselestat (ONO-6818) inhibits neutrophil elastase, reduces interleukin 8, C5B-9, and inflammation in cardiopulmonary bypass.</p>

<p>TMPRSS6-IN-1 (TFA) is a potent inhibitor of TMPRSS6 (Matriptase-2), a member of the TTSP family (a type of transmembrane serine protease). TMPRSS6 is a type II TTSP, and genetically reduced levels of TMPRSS6 have been shown to improve symptoms of hemochromatosis and β-thalassemia in mice.</p>

<p>JBJ-08-178-01, a mutant-selective tyrosine kinase inhibitor, targets (HER2) human epidermal growth factor receptor 2 and exhibits antitumoral activity. This compound not only diminishes HER2's kinase activity and protein levels through the induction of proteasomal degradation of the receptor but also shows promise in non-small-cell lung cancer research.</p>