JCP276 is a novel antibiotic and covalent inhibitor that disrupt M. tuberculosis growth by targeting multiple serine hydrolases.JCP276 is a narrow-spectrum inhibitor of Mycobacterium tuberculosis growth.JCP276 inhibits multiple nonessential serine hydrolases.JCP276 treatment caused accumulation of free lipids and a substantial decrease in lipooligosaccharides, linking SH inhibition to defects in cell envelope biogenesis.

IY7640 (IY-7640) is a small molecule targeting the stalk region of the influenza HA protein, blocks HA-mediated membrane fusion of H1N1, H3N2, and influenza B viruses in cells.IY7640 demonstrated potency against H1N1, H3N2, H5N1, H7N9, and H9N2 subtypes of IAV, including the 2009 pandemic H1N1 (pH1N1) virus (A/Korea/01/2009, rK09), with EC50 of 0.62-220 uM in plaque reduction assay in MDCK cells.IY7640 successfully inhibited rK09 replication in cells at a level comparable to that of oseltamivir, K09 HA fusion was inhibited only by 1 uM IY7640.The stalk region of the influenza HA protein is highly conserved across different (sub)types of influenza viruses.

HIV-1 Integrase inhibitor GS-B (GS-B) is a novel non-catalytic site integrase inhibitor of HIV-1 integrase (IN), inhibits the interaction between LEDGF IBD and IN with IC50 of 8.1 nM.GS-B displays antiviral potency in MT-4, MT-2, and human PBMCs with EC50 values of 18, 10, and 21 nM, respectively.

HIV-1 inhibitor 5b is a novel anti-HIV-1 compound that inhibits HIV-1 JR-CSF with EC50 of 1 nM without significant cytotoxicity (CC50>20 uM), also shows potency against NRTI- and NNRTI-resistant HIV-1 (EC50=1-3 nM); shows a chemical backbone similar to the clinically used integrase (IN) strand transfer inhibitor (INSTI) elvitegravir, but has no detectable INSTI activity; various drug-resistant HIV-1 strains did not display cross resistance to HIV-1 inhibitor 5b; remains its anti-HIV-1 activity even after the viral integration stage, significantly suppresses p24 antigen production in HIV-1 latently infected cells exposed with TNF-alpha; demonstrates favorable pharmacokinetic profiles in mice.

HHV protease inhibitor 43 is an irreversible small molecule inhibitor of human herpesvirus (HHV) protease targeting a non-catalytic cysteine (C161) with IC50 of 4 uM (HCMV), exhibits broad-spectrum inhibition of other HHV protease homologs.HHV protease inhibitor 43 demonstrates inhibitor stabilization of HCMV Pr homodimerization, exploiting a conformational equilibrium to block proteolysis.HHV protease inhibitor 43 causes a dose-dependent decrease in HCMV replication in HFF-1 cells with IC50 of 5 uM, with no significant cytotoxicity (CC50>20 uM).

GW461484A (GW-461484A) is a potent small molecule capable of restoring caspofungin sensitivity, inhibits Yck2 kinase in C. albicans, originally discovered as an inhibitor of human p38α with IC50 of 150 nM.GW461484A inhibited a very narrow spectrum of human kinases. At 1 uM, it showed >80% binding to only 10 additional human kinases out of a panel of >400 kinases.Yck2 is the proximal target of GW responsible for restoration of echinocandin sensitivity in C. albicans, potently inhibits Yck2 kinase activity in vitro and impairs the virulence of C. albicans in co-cultures and in mice.GW461484A potentiates conventional antifungals against a broad range of pathogens.

GSK693 (GSK-693) is a potent, direct inhibitor of M. tuberculosis enoyl-ACP reductase (InhA) with IC50 of 7 nM, shows equally potent activity against M. tuberculosis H37Rv both intra and extracellularly (MIC=0.2 uM); exhibits activities against multidrug (MDR) and extensively (XDR) drug-resistant clinical isolates as well as in TB murine models when orally dosed.

GSK3739936 (BMS-986180) is a potent, allosteric HIV-1 integrase (ALLINI), shows excellent potency in vitro against majority of the 124/125 variants (EC50=1.7 nM).

GSK-2336805 (JNJ-56914845) is a novel potent HCV NS5A inhibitor with multigenotype activity, has EC50s of 58.5, 7.4, and 53.8 pM on genotype 1a (H77), genotype 1b (Con-1 ET), and genotype 2a (JFH-1) replicon cells; shows an average EC50 of 63.7 pM on genotype 2a Jc1 virus, inhibits the HCV replication cycle and production of virus; retains activity on chimeric replicons containing NS5A patient sequences from genotype 1 and patient and consensus sequences for genotypes 4 and 5 and part of genotype 6.

GSK-229423 is a novel bacterial topoisomerase inhibitor that shows potent inhibition of supercoiling by DNA gyrase from S. aureus with IC50 of 14 nM; displays approximately 70 times more potent against S. aureus DNA gyrase than NXL101; has potent antibacterial activity against a broad spectrum of Gram-positive and Gram-negative bacterial pathogens, including clinical isolates with fluoroquinolone resistance mediated by DNA gyrase and topo IV mutations.

GRL-079 is a novel potent, nonpeptidic HIV-1 protease inhibitor with 2.5-30 nM against wild-type HIV-1NL4-3, 0.3-6.7 nM against HIV-2EHO, and 0.9-90 nM against laboratory-selected-PI-resistant HIV-1 and clinical HIV-1 variants resistant to multiple FDA-approved PIs (HIVMDR).

GHP-88309 (GHP88309) is a non-nucleoside, broad-spectrum allosteric inhibitor of paramyxovirus polymerase with EC50 of 0.9 uM against HPIV3-JS RdRP.Demonstrates highly potent antiviral potency against HPIV3-JS and clinical isolates HPIV3-9R4 and HPIV3-10L3 in the primary cell/virus isolate system (EC50=0.07-0.08 uM), without cytotoxicity.GHP-88309 targets a conserved microdomain in the L protein, inhibiting de novo RNA synthesis.GHP-88309 is efficacious in well-differentiated human airway epithelium cultures grown at air-liquid interface (3D-ALI-HBTEC).GHP-88309 (150 mg/kg b.i.d.) is orally efficacious in HPIV disease surrogate model.GHP-88309 possesses unusual broad-spectrum activity against diverse paramyxoviruses including respiroviruses (i.e. HPIV1 and HPIV3) and morbilliviruses (i.e. MeV).

GC-072 (GC072) is a potent, 4-oxoquinolizine antibiotic with selective inhibitory activity against bacterial topoisomerases (E. coli Topo II/DNA gyrase, IC50=0.18-1.5 uM).GC-072 demonstrated no detectable inhibition of human Topo I and II, is selective for bacterial topoisomerases (IC50>100 uM).GC-072 inhibits E. coli Quinolone-resistant gyrase (IC50=1.3-1.5 uM), S. aureus Gyrase and Topo IV (IC50=2-30 uM).GC-072 demonstrated good activity against B. pseudomallei, with an MIC90 of 0.25 ug/mL.GC-072 exhibited strong in vitro antimicrobial potency against biothreat agents Bacillus anthracis, Yersinia pestis, and Francisella tularensis and category B biothreat agent Burkholderia mallei.GC-072 is efficacious against B. pseudomallei aerosol infection in a mouse model following exposure to a 24-LD50 bacterial challenge.

GaMF1 is a novel antimycobacterial compound that targets the F1FO-ATP synthase γ subunit loop; GaMF1 is bactericidal and is active against multidrug- as well as bedaquiline-resistant strains. Combining GaMF1 with bedaquiline or novel diarylquinoline analogues showed potentiation without inducing genotoxicity or phenotypic changes in a human embryonic stem cell reporter assay. GaMF1 presents an attractive lead for the discovery of a novel class of anti-tuberculosis F-ATP synthase inhibitors.

Fluoxazolevir (NCGC00351982) is a potent, small molecule entry inhibitor of HCV with EC50 of 18.8 nM.Fluoxazolevir inhibits fusion of HCV with hepatic cells by binding HCV envelope protein 1 (E1) to prevent fusion.Fluoxazolevir was generally effective against all chimeric HCV-RLuc genotypes including 1a, 1b, 2b, 3a, 4a, 5a, 6a and 7a, was most effective against HCV 2a and 2b, followed by 3a and 6a, all within sub-μM EC50 values, with little to no cytotoxicity (CC50>20 uM).Fluoxazolevir was highly synergistic with other anti-HCV drugs (interferon-α, ribavirin, daclatasvir, sofosbuvir and simeprevir (NS3/4A protease inhibitor)).Fluoxazolevir suppresses HCV infection in humanized chimeric mice, and is active against multidrug-resistant HCV.Fluoxazolevir also broadly blocked human coronavirus entry into various cell types, inhibit SARS-CoV S- and SARS-CoV-2 S-mediated infection MA104 cells with EC50 of 6.49 and 3.86 uM, respectively.

FIM1033 (FIM-1033) is a potent small-molecule inhibitor of FimH with HAI EC90 of 8 nM, with antibiotica activities, significantly attenuated bacterial loads in pyelonephritis in treated mice.

Filovirus inhibitor compd-A is a small molecule filovirus entry inhibitor targeting the endosomal receptor NPC1 binding site, shows potent inhibitory activity against both Ebola and Marburg viruses with IC50 of 0.86 uM against pseudotyped Marburg virus entry.

FG944 (FG-944) is a potent selective LpxC inhibitor with MIC50 of 0.5 ug/mL against K.pneumoniae, synergizes with rifampin in carbapenem resistant K. pneumoniae and E. coli.

FD028 is a small-molecule HIV-1 inactivator by conjugating FD016 (gp120-CD4 binding inhibitor) with FD017 (HIV-1 fusion inhibitor), inactivates cell-free virions (IC50=0.7 uM) of by targeting both HIV-1 gp120 and gp41.FD028 is not significantly toxic and has broad-spectrum HIV-1 inhibitory and inactivation activity, including T20-resistant viruses and T2635-resistant viruses.

FC-8052 (FC8052) is a highly potent inhibitor of HIV-1 Nef-effector kinase, binds to recombinant Nef in vitro with Kd of 10 pM; FC-8052 inhibits Nef-dependent HIV-1 replication in PBMCs in the subnanomolar range.

EC-11716 (EC/11716) is a novel mycobacterium tuberculosis gyrase inhibitor with potent anti-tubercular activity (MIC 0.38 uM, M. tuberculosis H37Rv).EC/11716 is active against M. abscessus subspecies and clinical isolates, maintains comparable activity against a panel of clinical isolates covering the M. abscessus complex.EC/11716 is effective against M. abscessus biofilms (MIC 0.78 uM), with better bactericidal activity against biofilms than moxifloxacin.EC/11716 is active against M. abscessus in vivo.

Durlobactam is a novel beta-lactamase inhibitor for treatment of resistant bacterial infections.

DNA gyrase inhibitor EN-7 (EN-7) is a potent bacterial DNA gyrase inhibitor, is active against pathogenic species that are resistant to ciprofloxacin and other clinically important antibiotics.EN-7 inhibited growth of the wild-type strain (S. aureus) with MIC 1 μM.Strains containing GyrA A34T (mut-3 and mut-9), GyrA P219Q (mut-6), and GyrB K417E (mut-1, mut-2, mut-4, and mut-5) exhibited moderate resistance, with MICs of either 4 or 8 μM.EN-7 inhibited sporulation pathway in the bacterial genus Streptomyces.

DMA-135 (DMA135) is a RNA-biased small molecule binds to the EV71 SLII IRES domain (Kd=520 nM), dose-dependently (IC50=7.54 uM) inhibits EV-71 viral translation and replication.DMA-135 inhibits EV71 replication by attenuating IRES-dependent translation at dosages of relatively low cellular toxicity.DMA-135 changes the local and global structure of the EV71 SLII IRES domain.DMA-135 allosterically stabilizes a AUF1 (cellular protein)-SLII-(DMA-135) ternary complex.

DMA-135 (DMA135) is a RNA-biased small molecule binds to the EV71 SLII IRES domain (Kd=520 nM), dose-dependently (IC50=7.54 uM) inhibits EV-71 viral translation and replication.DMA-135 inhibits EV71 replication by attenuating IRES-dependent translation at dosages of relatively low cellular toxicity.DMA-135 changes the local and global structure of the EV71 SLII IRES domain.DMA-135 allosterically stabilizes a AUF1 (cellular protein)-SLII-(DMA-135) ternary complex.

Dichlorcyclizine (DCCZ) is a potent, small molecule HCV fusion inhibitor, also inhibits SARS-CoV and SARS-CoV-2 S-mediated infection in MA104 cells with EC50 of 9.92 and 4.53 uM, respectively.

CTN1122 (CTN-1122) is a potent, selective Leishmaniacasein kinase 1 isoform 2 (CK1.2, L-CK1.2) with IC50 of 0.72 uM (LmCK1) and 0.8 uM (amastigotes L. major), antileishmanial compound.

CTCB-405 (CTCB405) is a small molecule allosteric inhibitor of T. brucei phosphofructokinase (TbPFK) with IC50 of 0.18 uM, ITC Kd of 92 nM, no significant inhibition of human PFKs.CTCB-405 demonstrated in vitro parasite killing potency of the bloodstream form of T. brucei strain Lister 427 (EC50=0.37 uM).CTCB-405 (50, 100 mg/kg) clear parasites in a stage 1 model of HAT infection with 1-day oral dosing and show reduction of parasitaemia in the brain in a pleiomorphic model.

COR588 is a second-generation small-molecule lysine-gingipain (Kgp, gingipain K) inhibitor with novel structure and improved pharmacologic and safety profile prioritized for Alzheimer’s development.

COR388 (Atuzaginstat) is an orally bioavailable, brain penetrant small-molecule that irreversibly inhibits lysine-gingipain (Kgp, gingipain K) with Ki of <0.01 nM.COR388 blocks the activity of gingipains, a type of toxic protein made by the bacteria Porphyromonas gingivalis ( P. gingivalis ).COR388 reduced the bacterial load of an established P. gingivalis brain infection, blocked Aβ1-42 production, reduced neuroinflammation, and rescued neurons in the hippocampus.