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).

HH-N25 is a a potent and selective topoisomerase I (TOP1) inhibitor with potent antiproliferative activities against a panel of human breast cancer cell lines (IC50=0.045-4.2 uM).HH-N25 shows potent antitumor activities in human breast cancer cells in vitro and in vivo.

HF50731 (HF-50731) is a novel potent, selective CXCR4 antagonist with Ki of 19.8 nM in the CXCR4 competitive binding assay.HF50731 significantly inhibited SDF-1α-induced calcium mobilization (IC50=621 nM) and cell migration, and blocked HIV-1 infection via antagonizing CXCR4 coreceptor function (IC50=1.5 uM).The structure-activity relationship analysis demonstrated that HF50731 could primarily occupy the minor subpocket of CXCR4 and partially bind in the major subpocket by interacting with residues W94, D97, D171, and E288.

HEI3090 (HEI-3090) is a small-molecule P2RX7 activator (positive modulator) of purinergic P2RX7 receptor (P2X7R), enhances the P2RX7-mediated intracellular calcium concentration (Emax=250 nM).HEI3090 inhibits tumor growth and combined with αPD-1 immunotherapy ameliorates mice survival.Dendritic cells (DCs) mediate the antitumor activity induced by HEI3090.HEI3090 induces the production of mature IL-18 in the presence of eATP, triggers antitumor responses mediated by IL-18-induced NK and CD4+ T cells.HEI3090 combined with αPD-1 induces antitumor memory immune response.

HDAC8 PROTAC 1 is a first-in-class proteolysis targeting chimera (PROTAC) for selective degradation of histone deacetylase 8 (HDAC8).HDAC8 PROTAC 1 induced degradation of HDAC8 without affecting the levels of other HDACs in cellular assays, and inhibited the growth of T-cell leukemia Jurkat cells more potently than a conventional HDAC8 inhibitor.

HCN4 inhibitor EC18 (EC18) is a HCN4-prefering blocker.

H210 is a potent dual Mdm2/MdmX inhibitor with Ki of 9.66/2.89 nM, respectively.

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.

GW440139B is a potent RIPK3 inhibitor, suppresses necroptosis driven by dimerizable RIPK3 with IC50 of 73.6 nM.GW440139B inhibits TNF- and TRIF-mediated necroptosis independent of RIPK1-RIPK3 interaction, directly inhibited RIPK3-mediated MLKL phosphorylation at Ser345, thus inhibiting necroptosis.

GSK812397 is a potent, selective, noncompetitive, orally available antagonist of CXCR4 receptor, inhibits entry of X4-tropic strains of HIV-1 with IC50 of 4.60 nM and 1.50 nM in PBMCs and HOS assays, respectively; does not block CCR5-mediated viral entry in the R5 viral HOS assay (IC50>25 uM); produces a concentration-dependent decrease in both an SDF-1-mediated chemotaxis and intracellular calcium release (IC50=0.34 nM and 2.41 nM, respectively) in cell-based functional assays; demonstrates antiviral activity against a broad range of X4-utilizing strains of HIV-1.

GSK737 (GSK-737) is a potent, highly selective BET BD2 inhibitor with pIC50 of 7.3 (BRD4 BD2), 200-fold selectivity over BRD4 BD1.

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.

GSK669 is a potent, selective NOD2 (nucleotide-binding oligomerization domain 2) inhibitor, inhibits muramyl dipeptide (MDP)-induced NOD2-mediated signaling (IC50=0.5 uM), has an IC50 of 3.2 uM for MDP-stimulated IL-8 secretion in HEK293/hNOD2 cells.GSK669 specifically inhibits MDP-induced NOD2 activation, has no effect on IL-8 secretion induced by over-expression of NOD1.GSK669 significantly inhibits platelet proinflammatory cytokine release induced by muramyl dipeptide, platelet aggregation, ATP release, and ROS generation induced by collagen and collagen related peptide (CRP). GSK669 inhibits thrombosis and oxidative stress via targeting platelet glycoprotein VI (GPVI), decreases malonaldehyde (MDA) and increases superoxide dismutase (SOD) levels in mouse plasma

GSK-588045 is a potent and selective 5-HT1A/B/D receptor antagonist with Ki of 9.5/8.8/9.8, respectively; exhibits high selectivity over human hERG potassium channels, favorable pharmacokinetics, and excellent activity in vivo in rodent pharmacodynamic (PD) models; demonstrates potential as a faster acting antidepressant/anxiolytic with reduced side-effect burden.

GSK-5498A is a potent, selective small molecule blocker of Calcium-Release Activated Calcium (CRAC) channel with IC50 of 1 uM; completely inhibits calcium influx through CRAC channels, inhibits mediator release from mast cells, and pro-inflammatory cytokine release from T-cells from multiple human and rat preparations.

GSK3β-IN-1a is a relatively selective and potent GSK-3β inhibitor with IC50 of 64 nM; induces replication of growth-arrested R7T1 β cells in a dose-dependent manner with EC50 of 1.1 uM, likely mediates β-cell proliferation through the Wnt signaling pathway.

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).

GSK3735967 is a potent, selective, non-nucleoside inhibitor of DNMT1 with IC50 of 40 nM.

GSK3543105 is a potent, selective, non-nucleoside inhibitor of DNMT1 with IC50 of 33 nM.

GSK-2945 is a potent and selective small molecule Rev-Erbα agonist with EC50 of 50 nM, displays >1,000-fold selectivity over LXRα; inhibits LPS induction of IL-6 production and to upregulate expression of ABCA1 in human THP-1 cells; demonstrates in vivo bioavailability and orally active.

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.

GSK-2239633 is a potent, selective, allosteric CCR4 antagonist with pIC50 of 7.96; also inhibits TARC-induced increases in the F-actin content of isolated human CD4+ CCR4+ T-cells with pA2 of 7.1.

GSK2194069 is a potent and specific inhibitor of the β-ketoacyl reductase (KR) activity of human fatty acid synthase (hFAS) with IC50 of 7.7 nM (CoA release); shows an IC50 of 29 nM versus hFAS with acetoacetyl-CoA as the substrate, but shows little or no inhibition with β-hydroxybutyrylCoA and crotonyl-CoA (IC50 >1,000 nM), also does not inhibit the partial activities of the KS domain; decreases phosphatidylcholine levels in A549 cells with IC50 of 15.5 nM without effect on FAS protein levels, reduced A549 cell growth with EC50 of 15 nM.

GSK217 (GSK-217) is a potent, highly selective BET BD2 inhibitor with pIC50 of 7.5 (BRD4 BD2), 300-fold selectivity over BRD4 BD1.

GSK205 derivative 16-8 is a specific small molecule dual-inhibitor of TRPV4 and TRPA1 with IC50 of 0.45 and 0.41 uM, respectively; displays no inhibitory potency toward TRPV1, TRPV2 and TRPV3; effectively attenuates formalin-evoked trigeminal irritant pain in model of acute pancreatitis.

GSK-1842799 is a potent, selective, oral bioavailable S1P1 agonist with bind affinity of 0.52 nM; displays an excellent selectivity (>3,000-fold) for S1P1 over S1P3; significantly reduces blood lymphocyte at 3 mg/kg, achieves efficacy equivalent to FTY720 in the mouse EAE model of MS.

GSK180 (GSK-180) is a potent and specific inhibitor of kynurenine-3-monooxygenase (KMO) with IC50 of 6 nM, shows negligible activity against other enzymes on the tryptophan pathway; inhibits the convertion of kynurenine to 3-hydroxykynurenine with IC50 of 2.0 uM in cell-based assays; prevents multiple organ failure in rodent models of acute pancreatitis.

GSK145A is a small molecule inhibitor of SUMO-conjugating enzyme E2 with IC50 of 12.5 uM, GSK145A is competitive with the sumoylation of the TRPS1 peptide substrates.

GSK143 is a highly potent, selective, orally efficacious Syk inhibitor with pIC50 of 7.5, >600-fold selective over ZAP-70; inhibits anti-IgM induced Erk1/2 phosphorylation in Ramos cells with pIC50 of 7.1, and anti-IgM induced CD69 surface expression in primary B cells with pIC50 of 6.6; shows good efficacy in the rat Arthus model.