A specific inhibitor of MDA-9/Syntenin activity that inhibits MDA-9/Syntenin binding to EGFRvIII.

Selective 5-HT1B serotonin receptor antagonist

Jh-X-119-01 is a novel potent and selective interleukin-1 receptor-associated kinases 1 (IRAK1) inhibitor. JH-X-119-01 irreversibly labels IRAK1 at C302. This compound exhibited cytotoxic activity at single digit micromolar concentrations in a panel of WM, DLBCL, and lymphoma cell lines expressing MYD88. Cotreatment of JH-X-119-01 with the BTK inhibitor ibrutinib resulted in synergistic killing effects in these systems.

SAR405 R enantiomer is the less active enantiomer of SAR405. SAR405 is an inhibitor of PIK3C3/Vps34.

Novel potent and selective NADPH oxidase inhibitor, targeting Nox4 in TGFβ-induced lens epithelial to mesenchymal transition

PRN1371 is an irreversible covalent FGFR1-4 kinase inhibitor, with IC50s of 0.6, 1.3, 4.1, 19.3 and 8.1 nM for FGFR1, 2, 3, 4 and CSF1R, respectively.

Zidebactam, also known as WCK-5107, is a Beta lactamase inhibitor. Zidebactam is a novel Inhibitor of PBP2 Showing Potent "β-Lactam Enhancer" Activity against Pseudomonas aeruginosa, Including Multidrug-Resistant Metallo-β-Lactamase-Producing High-Risk Clones. Zidebactam demonstrated specific high-affinity binding to PBP2 of A. baumannii (0.01 μg/ml for both of the compounds). The MIC of zidebactam was >1,024 μg/ml for wild-type and multidrug-resistant Acinetobacter strains. Zidebactam is a PBP2 inhibitor that show a potent β-lactam enhancer effect against A. baumannii, including a multidrug-resistant OXA-23-producing ST2 international clone.

PAP-1 is a selective inhibitor of Kv1.3, voltage-gated K+ channel. PAP-1 (EC50=2 nM) potently inhibits human T effector memory cell proliferation and delayed hypersensitivity. IC50 value: 2 nM (EC50) [1]in vitro: blocks Kv1.3 in a use-dependent manner, with a Hill coefficient of 2 and an EC50 of 2 nM, by preferentially binding to the C-type inactivated state of the channel. PAP-1 is 23-fold selective over Kv1.5, 33- to 125-fold selective over other Kv1-family channels, and 500- to 7500-fold selective over Kv2.1, Kv3.1, Kv3.2, Kv4.2, HERG, calcium-activated K+ channels, Na+,Ca2+, and Cl- channels [1]. The blockade of Kv1.3 results in membrane depolarization and inhibition of TEM proliferation and function. In this study, the in vitro effects of PAP-1 on T cells and the in vivo toxicity and pharmacokinetics (PK) were examined in rhesus macaques (RM) with the ultimate aim of utilizing PAP-1 to define the role of TEMs in RM infected with simian immunodeficiency virus (SIV). Electrophysiologic studies on T cells in RM revealed a Kv1.3 expression pattern similar to that in human T cells. Thus, PAP-1 effectively suppressed TEM proliferation in RM [2].in vivo: PAP-1 does not exhibit cytotoxic or phototoxic effects, is negative in the Ames test, and affects cytochrome P450-dependent enzymes only at micromolar concentrations. PAP-1 potently inhibits the proliferation of human TEM cells and suppresses delayed type hypersensitivity, a TEM cell-mediated reaction, in rats [1]. When administered intravenously, PAP-1 showed a half-life of 6.4 hrs; the volume of distribution suggested extensive distribution into extravascular compartments. When orally administered, PAP-1 was efficiently absorbed. Plasma concentrations in RM undergoing a 30-day, chronic dosing study indicated that PAP-1 levels suppressive to TEMs in vitro can be achieved and maintained in vivo at a non-toxic dose [2].

Lu AF27139 is a novel rodent-active and CNS-penetrant P2X7 receptor antagonist. Lu AF27139 is highly selective and potent against rat, mouse, and human forms of the receptors. The rat pharmacokinetic profile is favorable with high oral bioavailability, modest clearance (0.79 L/(h kg)), and good CNS permeability. Importantly, Lu AF27139 was without effect in standard in vitro and in vivo toxicity studies. Lu AF27139 is a valuable tool for probing the role of the P2X7 receptor in rodent models of CNS diseases.

Rasarfin is a novel dual Ras and ARF6 inhibitor. Rasarfin blocks agonist-mediated internalization of AT1R and other GPCRs. Rasarfin also potently inhibits agonist-induced ERK1/2 signaling by GPCRs, and MAPK and Akt signaling by EGFR, as well as prevents cancer cell proliferation. In silico modeling and in vitro studies reveal a unique binding modality of Rasarfin within the SOS-binding domain of Ras. Rasarfin is a novel dual Ras and ARF6 inhibitor. Rasarfin blocks agonist-mediated internalization of AT1R and other GPCRs. Rasarfin also potently inhibits agonist-induced ERK1/2 signaling by GPCRs, and MAPK and Akt signaling by EGFR, as well as prevents cancer cell proliferation. In silico modeling and in vitro studies reveal a unique binding modality of Rasarfin within the SOS-binding domain of Ras.

Supinoxin, also known as RX-5902, is orally bioavailable small molecule inhibitor of phosphorylated-p68 RNA helicase (P-p68), with potential anti-proliferative and antineoplastic activity. Upon oral administration, P-p68 inhibitor RX-5902 may both inhibit the activity of the anti-apoptotic B-cell lymphoma 2 (Bcl-2) protein and facilitate the induction of cyclin-dependent kinase inhibitor 1 (p21). This may prevent G2/M cell cycle progression and lead to growth inhibition in tumor cells. P-p68 is overexpressed in various types of solid tumors but absent in normal tissues, and plays a role in tumor progression and metastasis.

MKT-077 (FJ-776) is a highly water-soluble (>200 mg/ml) rhodacyanine dye that exhibits significant antitumor activity, binds to Hsp70 family member, mortalin (mot-2), and abrogates its interactions with p53.

GPR52-IN-43(CAY10786) is a novel GPR52 antagonist, reducing mHTT levels by targeting GPR52 and promoting survival of mouse primary striatal neurons, and also reducing HD-related phenotypes in HdhQ140.

Compound 101 (GRK2 inhibitor 101, Takeda compound 101, Cmpd101) is a novel membrane-permeable, small-molecule inhibitor of GRK2 and GRK3.

D-Luciferin sodium is heterocyclic light-emitting compound and natural ligand for luciferase used to detect cell activity. It requires ATP for its reaction, emitting a greenish-yellow luminescence at a peak wavelength of approximately 530 nm. The salt form of luciferin dissolves in water or other typical buffers.

M1001 is a novel allosteric agonist of hypoxia-inducible factor-2α subunit (hif-2α), significantly displacing pocket residue y281

ZZW-115 (ZZW115, ZZW 115) is a potent inhibitor of NUPR1 (Kd=2.1 uM), an intrinsically disordered protein (IDP) with an entirely disordered conformation.

Cell-permeable, irreversible inhibitor of caspase-3/CPP32; inhibits tumor cell apoptosis. Neuroprotective in rat hippocampus following seizures in vivo.

Z-IETD-FMK is a specific Caspase-8 inhibitor.

ICG amine, as a near-infrared fluorescent probe, binds to amino acid residues without condensing agents. ICG is a tricarbocyanine dye.

Ganaplacide (KAF156, GNF-156) is a novel antimalarial clinical candidate that shows blood schizonticidal activity with IC50 of 6-17.4 nM against P falciparum drug-sensitive and drug-resistant strains.

SKA-31 (Naphtho[1,2-d]thiazol-2-ylamine) is a potent activator of potassium channel with EC50 of 260 nM, 1.9 μM, 2.9 μM, and 2.9 μM for KCa3.1, KCa2.2, KCa2.1 and KCa2.3, respectively.

Alexamorelin is a synthetic growth hormone (GH) secretagogue.

GSK2837808A is a potent, selective lactate dehydrogenase A (LDHA) inhibitor (IC50 values are 1.9 and 14 nM for LDHA and LDHB respectively).

BI 671800 is a potent, oral prostaglandin D2 receptor (CRTH2) antagonist for treatment of asthma..

HCV-IN-30 (compound 48) is a HCV NS5A replication complex inhibitor, with IC50s of 901 and 102 nM for genotypes 1a and 1b replicons, respectively.

SPDB is a disulfide chemical linker for antibody-drug conjugates (ADCs)..

Opicapone(BIA 9-1067) is a long-acting, peripherally selective inhibitor of catechol-O-methyltransferase.

RTICBM-189 is a Urea derivative and a CB1 allosteric modulator. RTICBM-189 showed no activity at >50 protein targets and excellent brain permeation but relatively low metabolic stability in rat liver microsomes. Pharmacokinetic studies in rats confirmed the excellent brain exposure of 31 with a brain/plasma ratio Kp of 2.0. Importantly, intraperitoneal administration of RTICBM-189 significantly and selectively attenuated the reinstatement of the cocaine-seeking behavior in rats without affecting locomotion.