e-64

E-64 (Proteinase inhibitor E 64) is an irreversible and specific inhibitor of cysteine proteases, exhibiting an IC50 of 9 nM for papain.

GNE-6468 is a potent and selective agonist of RORγ(RORc) (EC50: 13 nM for HEK-293 cell).

NSC-5844 (RE-640) (RE640) is a bisquinoline compound with C-C chemokine receptor type 1 (CCR1)-agonistic activities.

LtaS-IN-1 is an effective inhibitor of Lipoteichoic acid synthesis in multidrug-resistant (MDR) E. faecium and by altering the cell wall morphology. LtaS-IN-1 is against Enterococcus spp 28 strains with varying MIC values ranging from 0.5 μg mL to 64 μg mL. LtaS-IN-1 inhibits strain E1630 and E1590 with MIC values of 0.5 μg mL.

DNA ligase-IN-2 (compound 2) acts as a potent LigA inhibitor, effectively hindering the DNA-independent spontaneous adenylation activity of full-length LigA and the truncated enzyme LigA:AD with an IC50 of 29 nM. It also significantly suppresses the in vitro growth of Staphylococcus aureus, showing MIC values of 1 μg mL for S. aureus ATCC 29213 and S. aureus ATCC 700699, while the MIC for Escherichia coli (E. coli) ATCC 25922 is >64 μg mL.

Antiangiogenic agent 8 (Compound 3m) functions as both an antibacterial agent and an antiangiogenic compound. It shows minimum inhibitory concentrations (MIC) of 16, 8, 4, 16, and 8 μg mL against E. coli, P. aeruginosa, B. subtilis, S. aureus, and C. glabrata, respectively, with minimum bactericidal concentrations (MBC) ranging from 32 to 64 μg mL. This compound holds potential for applications in infection control and cardiovascular disease research.

2-deoxy-D-Glucose-13C6is intended for use as an internal standard for the quantification of 2-deoxy-D-glucose by GC- or LC-MS. 2-deoxy-D-Glucose is a glucose antimetabolite and an inhibitor of glycolysis.1,2It inhibits hexokinase, the enzyme that converts glucose to glucose-6-phosphate, as well as phosphoglucose isomerase, the enzyme that converts glucose-6-phosphate to fructose-6-phosphate.32-deoxy-D-Glucose (16 mM) induces apoptosis in SK-BR-3 cells, as well as inhibits the growth of 143B osteosarcoma cells cultured under hypoxic conditions when used at a concentration of 2 mg ml.4,5In vivo, 2-deoxy-D-glucose (500 mg kg) reduces tumor growth in 143B osteosarcoma and MV522 non-small cell lung cancer mouse xenograft models when used alone or in combination with doxorubicin or paclitaxel .6 1.Kang, H.T., and Hwang, E.S.2-Deoxyglucose: An anticancer and antiviral therapeutic, but not any more a low glucose mimeticLife Sci.78(12)1392-1399(2006) 2.Aft, R.L., Zhang, F.W., and Gius, D.Evaluation of 2-deoxy-D-glucose as a chemotherapeutic agent: Mechanism of cell deathBr. J. Cancer87(7)805-812(2002) 3.Ralser, M., Wamelink, M.M., Struys, E.A., et al.A catabolic block does not sufficiently explain how 2-deoxy-D-glucose inhibits cell growthProc. Natl. Acad. Sci. USA105(46)17807-17811(2008) 4.Liu, H., Savaraj, N., Priebe, W., et al.Hypoxia increases tumor cell sensitivity to glycolytic inhibitors: A strategy for solid tumor therapy (Model C)Biochem. Pharmacol.64(12)1745-1751(2002) 5.Zhang, X.D., Deslandes, E., Villedieu, M., et al.Effect of 2-deoxy-D-glucose on various malignant cell lines in vitroAnticancer Res.26(5A)3561-3566(2006) 6.Maschek, G., Savaraj, N., Priebe, W., et al.2-deoxy-D-glucose increases the efficacy of adriamycin and paclitaxel in human osteosarcoma and non-small cell lung cancers in vivoCancer Res.64(1)31-34(2004)

Resolvin E2 (RvE2) is a member of the specialized pro-resolving mediator (SPM) family of bioactive lipids.1It is produced from eicosapentaenoic acidviaan 18-HEPE intermediate, which is formed by aspirin-acetylated COX-2-mediated oxidation of EPA, by 5-lipoxygenase (5-LO) in human polymorphonuclear (PMN) neutrophils.2,3RvE2 (20 ng/animal) inhibits increases in inflammatory exudate neutrophil infiltration in a mouse model of peritonitis induced by zymosan A .3Hepatic RvE2 levels are increased in mice fed normal chow, as well as in a mouse model of high-fat diet-induced non-alcoholic fatty liver disease (NAFLD), by dietary supplementation with EPA.4Plasma levels of RvE2 are increased by dietary supplementation with fish oil containing ω-3 polyunsaturated fatty acids (PUFAs) in patients with peripheral artery disease or chronic kidney disease.1,5,6 1.Chiang, N., and Serhan, C.N.Specialized pro-resolving mediator network: An update on production and actionsEssays Biochem.64(3)443-462(2020) 2.Tjonahen, E., Oh, S.F., Siegelman, J., et al.Resolvin E2: Identification and anti-inflammatory actions: Pivotal role of human 5-lipoxygenase in resolvin E series biosynthesisChemistry & Biology131193-1202(2006) 3.Sungwhan, F.O., Pillai, P.S., Recchiuti, A., et al.Pro-resolving actions and stereoselective biosynthesis of 18S E-series resolvins in human leukocytes and murine inflammationJ. Clin. Invest.121(2)569-581(2011) 4.Echeverría, F., Valenzuela, R., Espinosa, A., et al.Reduction of high-fat diet-induced liver proinflammatory state by eicosapentaenoic acid plus hydroxytyrosol supplementation: Involvement of resolvins RvE1/2 and RvD1/2J. Nutr. Biochem.6335-43(2019) 5.Ramirez, J.L., Gasper, W.J., Khetani, S.A., et al.Fish oil increases specialized pro-resolving lipid mediators in PAD (the OMEGA-PAD II trial)J. Surg. Res.238164-174(2019) 6.Barden, A.E., Shinde, S., Burke, V., et al.The effect of n-3 fatty acids and coenzyme Q10 supplementation on neutrophil leukotrienes, mediators of inflammation resolution and myeloperoxidase in chronic kidney diseaseProstaglandins Other Lipid Mediat.1361-8(2018)

L-Pyrohomoglutamic acid is an amino acid building block.1,2It has been used in the synthesis of ligands for FK506-binding proteins (FKBPs) and histone deacetylase (HDAC) inhibitors. 1.Pomplun, S., Wang, Y., Kirschner, A., et al.Rational design and asymmetric synthesis of potent and neurotrophic ligands for FK506-binding proteins (FKBPs)Angew. Chem. Int. Ed.54(1)345-348(2015) 2.Taddei, M., Cini, E., Giannotti, L., et al.Lactam based 7-amino suberoylamide hydroxamic acids as potent HDAC inhibitorsBioorg. Med. Chem. Lett.24(1)61-64(2014)

AN3661, a potent antimalarial lead compound, targets a Plasmodium falciparum cleavage and polyadenylation specificity factor homologue subunit 3 (PfCPSF3) and inhibits Plasmodium falciparum laboratory-adapted strains, Ugandan field isolates, and murine P. berghei and P. falciparum infections[1].

Leoidin is a depsidone originally isolated from L. gangaleoides that has antibacterial and enzyme inhibitory activities.1,2,3 It is active against the bacteria E. faecalis, H. influenzae, M. catarrhalis, S. aureus, and S. pneumoniae (MICs = 8, 32, 1, 128, and 64 μg/ml, respectively).2 Leoidin inhibits phenylalanyl-tRNA synthetase (PheRS) isolated from P. aeruginosa (IC50 = 42 μM). It also inhibits organic anion-transporting polypeptide 1B1 (OATP1B1) and OATP1B3 with Ki values of 0.08 and 1.84 μM, respectively, in CHO cells expressing the human transporters.3

Feglymycin is a 13-amino acid peptide originally isolated from Streptomyces that has antibacterial and antiviral activities. It is active against Gram-positive bacteria (MICs = 32-64 μg/ml) and inhibits HIV viral replication in H9 cells (IC50 = ~5 μM). Feglymycin is also active against clinical isolates of HIV-1 from clades A-D, A/E, and G (EC50s = 0.5-6.7 μM). It interacts with gp120 and inhibits HIV-1 NL4.3 binding to human soluble CD4 (EC50 = 4.4 μM) and to CD4+ SupT1 T cells by 74.5% when used at a concentration of 10.5 μM. Feglymycin inhibits the E. coli peptidoglycan biosynthesis enzymes MurA and MurC (Kis = 3.4 and 0.3 μM, respectively) in a noncompetitive manner.

8Br-HA is an inhibitor of fragile histidine triad diadenosine triphosphatase (FHIT; IC50= 0.12 μM).1It inhibits the growth of HCC827 and H460 lung cancer cells (GI50s = 0.87 and 5.9 μM, respectively). 1.Kawaguchi, M., Sekimoto, E., Ohta, Y., et al.Synthesis of fluorescent probes targeting tumor-suppressor protein FHIT and Identification of apoptosis-inducing FHIT inhibitorsJ. Med. Chem.64(13)9567-9576(2021)

Antibacterial agent 50 (example 47) is a compound exhibiting antibacterial activity with minimum inhibitory concentration (MIC) values of 32, 64, and 128 mcg mL against E. coli strains NCTC 13351, M 50, and 7 MP, respectively [WO2013030733A1].

LpxC-IN-5 is a potent, non-hydroxamate inhibitor of LpxC, which is an enzyme known as UDP-3-O-acyl-N-acetylglucosamine deacetylase. It exhibits an IC50 value of 20 nM. Furthermore, LpxC-IN-5 displays antibacterial activity against various strains including E. coli ATCC25922, P. aeruginosa ATCC27853, K. pneumoniae ATCC13883, and P. aeruginosa 5567. The minimum inhibitory concentration (MIC) values for these strains are 16 μg/mL, 4 μg/mL, 64 μg/mL, and 4 μg/mL, respectively.

E 64c (EP 475) , a derivative of E-64, is an irreversible and membrane-permeant cysteine protease inhibitor.

Antibacterial Agent 135 (example 7) effectively inhibits various bacteria, including P. aeruginosa, A. baumannii, E. coli, and K. pneumoniae, with a minimum inhibitory concentration (MIC) greater than 64 μg mL [1].

Bombinin-BO1, an antimicrobial peptide from the skin secretions of the Bombina orientalis toad, exhibits activity against E. coli, S. aureus, and Candida albicans with minimum inhibitory concentration (MIC) values of 64, 64, and 128 mg L, respectively [1].

BING, a antimicrobial peptide discovered in Japanese medaka fish (O. laptipes), originates from vacuolar protein sorting-associated protein 13D-like (Vps13D). It exhibits efficacy against a range of Gram-negative and Gram-positive bacteria, notably including methicillin-resistant S. aureus (MRSA; MICs = 4-64 µg/ml). Furthermore, BING enhances the effectiveness of antibiotics such as ampicillin, amoxicillin, and novobiocin against P. aeruginosa, and it prevents resistance development to kanamycin and ampicillin in E. coli. Notably, its administration in vivo significantly improves survival rates in O. laptipes challenged with E. tarda.

(-)-Codonopsine is an alkaloid found in Codonopsis clematidea, exhibiting antibacterial and hypotensive properties. The minimum inhibitory concentration (MIC) value against Escherichia coli (E. coli) is 64 μg/mL. (-)-Codonopsine shows promise for research in anti-infective and cardiovascular applications.

Crabrolin is a 13-peptide that can be extracted from the venom of the European hornet (Vespa crabro). Its minimum inhibitory concentration minimum bactericidal concentration (MIC MBC) values against Staphylococcus aureus (S. aureus) (NCTC 10788), methicillin-resistant Staphylococcus aureus (MRSA) (NCTC 12493), and Enterococcus faecium (E. faecium) (NTCC 12697) are 2 2, 16 64, and 4 8 μM, respectively.