ONO-8055 is a highly selective and potent EP2/EP3 dual agonist with EC50 of 0.67/0.7 nM, shows >450-fold selectivity over EP4 receptors (EC50=339 nM); improves the lower urinary tract dysfunctions of neurogenic UAB in a rat lumber spinal canal stenosis model with twice-daily (bid) oral dosing of 0.01 mg/kg, demonstrates much higher in vivo efficacy than the currently used drug for UAB.

ONO-7579 (ONO7579) is a novel potent, selective, orally available pan-TRK inhibitor.BDNF significantly increased TRKB phosphorylation in GBC cells and the effects were abrogated by ONO-7579, suppress proliferation in a dose-dependent manner in TYGBK-1 cells.ONO-7579 inhibited BDNF/TRKB-induced migration and invasiveness, particularly in GBC cells harboring wild-type KRAS.ONO-7579 reduced invasiveness of gallbladder cancer (GBC) cells through inhibiting epithelial–mesenchymal transition (EMT) via the extracellular signal-regulated kinase (ERK) or protein kinase B (AKT) pathway.

NXT629 (NXT-629) is a potent, selective PPARα antagonist with IC50 of 77 nM (human PPARα), no effect against PPARδ and PPARγ (IC50>30 uM).NXT629 inhibited agonist-induced transcription of PPARα-regulated genes, demonstrating target engagement in chronic lymphocytic leukemia (CLL) cells.NXT629 induced apoptosis of CLL cells even in the presence of a protective microenvironment.NXT629 reduces the number of chronic leukemia cells undergoing cell division with IC50 of 9.6 uM.NXT629 reduces CLL tumor burden delays disease progression of CLL in CLL mouse model.

NVS-BPTF-1 is the first highly potent and selective BPTF-bromodomain inhibitor with IC50 of 56 nM in an AlphaScreen assay and Kd of 71 nM in a BLI assay.NVS-BPTF-1 displays no significant interaction in DSF screen and a BROMOscan against a panel of other human bromodomains.In HEK293 cells, NVS-BPTF-1 showed on-target activity with an IC50 of 16 nM, as measured by a nanoBRET assay.NVS-BPTF-1 did not affect the proliferation of multiple human cancer cell lines, and NVS-BPTF-1 did not affect the level of PSMB8 and PSMB9 or TAP1 and TAP2, unlike BPTF siRNA knockdown caused effect.

NU5455 (NU-5455) is a potent, highly selective, oral inhibitor of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) activity with IC50 of 8.2 nM.NU5455 displays selectivity versus Vps34 (8.7-fold), PI3Kδ (33.7-fold), ATM/ATR (both >1200-fold), 228-fold selectivity margin for DNA-PKcs kinase activity versus that of PI3Kα.NU5455 inhibited radiation-induced activation of DNA-PK with an IC50 of 168 nM, but did not inhibit IGF-stimulated activation of AKT in MCF7 cells even at 10 uM.NU5455 inhibited the repair of DNA-DSBs induced by treatment with enzyme AfeI or ScaI restriction endonucleases within a 24-hour period in HEK293T cells, significantly increased the number of colocalized γH2AX and 53BP1 foci.NU5455 is a highly selective inhibitor of DNA-PKcs that is active in cells and that can perturb DNA-DSB repair by NHEJ.NU5455 preferentially augmented radiotherapy in subcutaneous Calu-6 and A549 lung tumor xenografts, increased both the efficacy and the toxicity of a parenterally administered topoisomerase inhibitor, NU5455 enhanced the activity of doxorubicin released locally in liver tumor xenografts without inducing any adverse effect.

NSC81111 is a highly potent EGFR-TK inhibitor with IC50 of 0.15 nM; NSC81111 displays stronger antiproliferative activities than erlotinib with IC50 values of <10 uM overexpressed EGFR-TK cancer cell lines: A431 and HeLa.

NSC290956 is a small molecule inhibitor of KRas with Kd of 21.3 uM.NSC290956 inhibits KRas activity and downstream signaling events in KRas-driven nuytant NSCLC cells, decreases the cellular viability, cell cycle, and migration.NSC290956 changes KRas-dependent metabolic phenotype in Non-small-cell lung cancer cells, regulates mitochondrial dysfunction for apoptosis in both A549 and H358 cells.NSC290956 shows activity in the KRas mutant cell line xenograft.

NRT-870-59 is a potent, reversible PTP4A3 inhibitor (IC50=86 nM) with inhibitory specificity for PTP4A3 versus both PTP4A3 A111S mutant and CDC25B.NRT-870-59 does not inhibit CDC25B and PTP4A3 A111S mutant at 1 uM, and 5- to 6-fold less potent aginst DUSP3.NRT-870-59 inhibits PTP4A1, PTP4A2, PTP4A3 mutants C49S, K144I and A106V with IC50 of 133.2, 264.4, 86.0, 332.2, 180.2 and 57.7 nM, respectively.NRT-870-59 inhibits cancer cell colony formation, which is required PTP4A3 expression.The PTP4A (phosphatase of regenerating liver/PRL) phosphatases are a unique subfamily of protein tyrosine phosphatases (PTPs) comprising three highly homologous members (PTP4A1, PTP4A2, and PTP4A3) with 80% amino acid sequence identity.PTP4A3, and to a lesser extent PTP4A1 and PTP4A2, are overexpressed in many types of cancer, promote tumor invasion and dissemination, and contribute to poor patient prognosis.

NR-160 (NR160) is a novel potent, selective inhibitor of histone deacetylase 6 (HDAC6) with IC50 of 30 nM, shows SI (75-1847 )over all HDAC class I isoforms.NR-160 induced α-tubulin acetylation (ac-α-tubulin) in treated acute myeloid leukemic (AML) cell line HL60, but not histone H3 (ac-H3) (a marker for the inhibition of class I HDACs).NR-160 enhances the cytotoxicity induction of bortezomib, epirubicin and daunorubicin on a panel of seven leukemia cell lines

NPG9 (NSR inhibitor NPG9) is a small molecule inhibitor of streptococcus agalactiaenisin resistance protein (NSR) with 58% inhibition at 100 uM (specific growth inhibition assay).

NPD4928 (NPD 4928) is a small molecule that enhances ferroptosis via inhibition of ferroptosis suppressor protein 1 (FSP1).NPD4928 enhanced the sensitivity of various cancer cells to GPX4 inhibitor RSL3.

NP627 (NP-627) is a specific small-molecule inhibitor of protein kinase C deltaI (PKCδI) with Kd of 1 nM.NP627 inhibits the cleavage of PKCδI in adipocyte (at 10 nM) and decreases PKCδI kinase activity.NP627 does not inhibit other PKC isozyme activities.NP627 prevents caspase-3 mediated cleavage of PKCδI, significantly inhibits PKCδI catalytic fragment release, decreases inflammation and apoptosis, and significantly improves mitochondrial metabolism in human adipocytes from obese individuals.

NP10679 (NP 10679) is a potent, orally active, NMDA receptor subunit 2B (GluN2B)-selective inhibitor of NMDA receptor with IC50 of 23 nM, with no significant effect on GluN2A/C/D (IC50>100 uM).NP10679 demonstrates high pH sensitivity, NP10679 exhibits both a potent IC50 at pH 6.9 of 23 nM with a ratio of IC50 at pH 7.6 to that at pH 6.9 (referred to as pH Boost) of 6.2 fold.NP10679 reduced infarct volume n a dose-dependent manner with an ED50 of 1 mg/kg IP dose and a maximum infarct volume reduction of 52% in MCAo experiments.NP10679 perturbed motor coordination or function in mice.

NOS31 is a potent, selective NADPH oxidase 1 (Nox1) inhibitor with IC50 of 2.0 uM.NOS31 inhibited ROS production in CaCO2 cells in a dose-dependent manner, inhibits NOXO1/NOXA1-induced ROS production.NOS31 is much less potent with other Nox enzymes Nox2, Nox3, Nox4, and Nox5 in HEK293 reconstitution systems (>15-fold selectivity).NOS31 inhibited the proliferation of several colon cancer cell lines in vitro (CaCO2, HT-29, DLD-1, RKO, and HCT-116), with no direct antioxidant activity nor cytotoxity.

NN-390 (NN390) is a potent, selective HDAC6 inhibitor with IC50 of 9.8 nM, >200-550-fold selectivity over other HDAC isoforms.NN-390 inhibits primary cells of treatment-refractory Group 3 MB cells (SU_MB002) with IC50 of 2.33 uM.NN-390 is the first HDAC6-selective inhibitor to show therapeutic potential in metastatic Group 3 medulloblastoma (MB), an aggressive pediatric brain tumor often associated with leptomeningeal metastases and therapy resistance.NN-390 selectively targets cell population with a 44.3-fold therapeutic margin between patient-derived Group 3 MB cells in comparison to healthy neural stem cells.NN-390 demonstrated a 45-fold increased potency over HDAC6-selective clinical candidate citarinostat.

NLRP3-IN-3 is a potent and selective inhibitor of NLRP3 inflammasome with IC50 of 1.26 nM in THP1 cells, showing good pharmacokinetic profiles with oral bioavailability.

NHB1109 is a potent, selective, orally active PTPRD phosphatase inhibitor with IC50 of 0.6 uM, displays selectivity over PTPRS, PTPRF, PTPRJ or PTPN1/PTP1B phosphatases.NHB1109 exhibited no substantial potency at other protein tyrosine phosphatases screened, no significant potency at any of the targets of clinically-useful drugs identified in EUROFINS screens.NHB1109 (200 mg/kg) is well tolerated by mice.NHB1109 is a good candidate to advance to in vivo studies in addiction paradigms and toward human use to reduce reward from addictive substances.

NH4-6 is a potent, selective pan SIRT1-3 inhibitor with IC50 of 3.0/0.032/2.3 uM for SIRT1/2/3, respectively.NH4-6 does not inhibits SIRT5 and SIRT6.NH4-6 (30 mg/kg) significantly impaired tumor growth in HCT-116 tumor xenograft.

NH4-13 is a potent, SIRT2-selective inhibitor with IC50 of 87 nM, no inhibition against SIRT1/3/5/6 (CI50>50 uM).NH4-13 (30 mg/kg) significantly impaired tumor growth in HCT-116 tumor xenograft.

NEU-4438 (NEU4438) is a potent inhibitor of P. falciparum with EC50 of 13 nM (T. brucei), demonstrates improved aqueous solubility (880 uM) compared to NEU-1953; reduced parasitemia 109 fold in trypanosome-infected mice.

NDI-031407 (NDI 031407) is a novel potent, selective TYK2 inhibitor with IC50 of 0.21 nM in radiometric assays, 20 fold selectivity over JAK3 (4.2 nM), 147 fold for JAK2 (31 nM), and 220 fold for JAK1 (46 nM).NDI-031407 has high potency in cell line and primary cell assays for TYK2-dependent cytokines (IL-12, IC50=118 nM) over TYK2-independent cytokines (GM-CSF).NDI-031407 blocks IL-23–induced STAT3 phosphorylation and IL-17A production in human CD4+ T cells.NDI-031407 inhibits disease progression in the SKG model of Spondyloarthritis (SpA).NDI-031407 suppresses systemic IL-23–induced type 3 immunity in vivo.

ND2158 (ND-2158) is a highly potent and selective IRAK4 inhibitor with IC50 of 1.3 nM; ND2158 demonstrates high selectivity against 334 kinases, and >1000-fold over IRAK1. ND2158 blocked TNF production, collagen-induced arthritis, and gout formation in mice, suppressed LPS-induced TNF production, alleviated collagen-induced arthritis, and blocked gout formation in mouse models. IRAK4 inhibition promoted killing of ABC DLBCL lines harboring MYD88 L265P, by down-modulating survival signals, including NF-κB and autocrine IL-6/IL-10 engagement of the JAK-STAT3 pathway. In ABC DLBCL xenograft models, IRAK4 inhibition suppressed tumor growth as a single agent, and in combination with the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib or the Bcl-2 inhibitor ABT-199.

NCATS-SM5637 (NSC 791985) is a potent, selective mutant IDH1 inhibitor with IC50 of 81/72 nM for IDH1 mutant R132H/R132C, respctively.NCATS-SM5637 showed higher tumoral concentrations that corresponded to lower 2-HG concentrations in engineered mIDH1-U87-xenograft mouse model, compared with the approved drug AG-120 (ivosidenib).

NBI-98782 (alpha-dihydrotetrabenazine) is a potent, selective vesicular monoamine transporter (VMAT2, SLC18A2) inhibitor with Ki of 0.97 nM.Acute NBI-98782 decreased mPFC, dSTR, hippocampus, and NAC DA, 5-HT, and NE efflux, while increasing that of DOPAC, HVA, and 5-HIAA.NBI-98782 suppressed clozapine-, olanzapine- and risperidone-induced DA efflux in both mPFC and dSTR, and ACh efflux in mPFC.NBI-98782 attenuated PCP-induced DA, 5-HT, NE and Glu efflux, and AMPH-induced DA and NE efflux, in both mPFC and dSTR, as well as PCP- and AMPH-induced hyperlocomotion.

NBD-14273 is a CD4-mimetic, small-molecule HIV-1 entry inhibitor with IC50 of 0.13 uM.NBD-14273 showed both improved antiviral activity and selectivity index (SI) against HIV-1HXB2 compared to NBD-14136.NBD-14273 displayed potenct against a large panel of 50 HIV-1 Env-pseudotyped viruses representing clinical isolates of diverse subtypes.

NaV1.7 inhibitor 51 is a highly potent, selective, orally active NaV1.7 inhibitor with IC50 of 10.7 nM in FLIPR membrane potential assay, no significant activity against NaV1.5 (IC50>10 uM).NaV1.7 inhibitor 51 shows good selectivity against other NaV isoforms and minimal inhibition at 10 uM for the resting state across different NaV isoforms.NaV1.7 inhibitor 51 exhibits state-dependent block of human, monkey, and mouse NaV1.7 with a similar potency range.NaV1.7 inhibitor 51 shows significant effects on the CCI-induced neuropathic pain model.

NAH-C3-GPKK is a potent, selective protein N-terminal methyltransferase 1 (NTMT1) bisubstrate inhibitor with Kiapp of 7 nM in endogenous proteomes.NAH-C3-GPKK also potently inhibit a methyltransferase complex HemK2-Trm112 (also known as KMT9-Trm112, IC50=0.3 uM).NAH-C3-GPKK is the first potent inhibitor for HemK2/KMT9.

N205 is a novel anti-malaria compound with in vitro IC50 of 1.3 nM against Plasmodium falciparum (3D7); demonstrates excellent rodent pharmacokinetic and in vivo antimalarial efficacy studies in the mouse Plasmodium berghei and Plasmodium falciparum Pf3D70087/N9 severe combined immunodeficiency (SCID) mouse models.

MyoMed-946 is a small moelcule that inhibits MuRF1 (TRIM63) activity and MuRF1/MuRF2 expression; MyoMed-946 inhibits MuRF1 expression/activity in vivo and is able to attenuate skeletal muscle atrophy and dysfunction in mice treated with monocrotaline to induce right ventricular hypertrophy and subsequent cardiac cachexia. MyoMed-946 attenuates skeletal muscle strength loss in mouse model for type 2 diabetes mellitus (T2DM), with no significant effects on serum glucose. MyoMed-946 attenuates induction of MuRF1 in tumor stressed muscles. MyoMed-946 also rescues citrate synthase and complex-1 activities in tumor-stressed muscles. MuRF1 (muscle-specific RING finger protein-1) is a muscle-specific ubiquitin ligase that regulates muscle catabolism during chronic wasting states, both MuRF1 and MuRF2 participate in glucose and, also, in lipid regulation.

MV1035 (MV-1035) is a novel small molecule that reduce U87 GBM cells migration and invasiveness, targeting m6A demethylase ALKBH5, also inhibits ALKBH2; MV1035 directly inhibits active recombinant ALKBH5 protein and, consequently, negatively regulates CD73 protein expression without affecting CD73 mRNA transcription. In PD-GSCs, MV1035 has a synergistic effect with TMZ in reducing cell viability and their ability to form spheres. MV1035 is able both to reduce the expression of MGMT and to inhibit ALKBH2 activity.