A potent, selective sigma 1 ligand with Ki of 0.08 nM, >3000-fold selectivity over sigma 2 (Ki=1377 nM).

A potent, selective sigma-2 receptor agonist with Ki of 16.5 nM, 200-fold selectivity over sigma 1 (Ki=3063 nM).

A potent, selective sigma-2 receptor agonist with Ki of 3.5 nM, 25-fold selectivity over sigma-1 receptors (Ki=86.6 nM).

A potent, selective small molecule inhibitor of transcription factor STAT5b with Ki of 44 nM, >50-fold selectivity over STAT5a..

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].

A potent, selective small molecule Mcl-1 inhibitor that selectively targets the BH3-binding groove of Mcl-1.

A potent, selective sodium-coupled citrate transporter (NaCT or SLC13A5) with IC50 of 0.51 uM, >20-fold selectivity over NaDC1 and NaDC3.

A potent, selective Src and Syk kinase inhibitor with IC50 of 29.3 uM and 2.5 uM, respectively.

A potent, selective STAT3 inhibitor that blocks STAT3 binding to its phosphopeptide ligand (IC50=20 uM) and inhibits IL-6-mediated phosphorylation of STAT3.

A potent, selective STAT3 inhibitor with IC50 of 9.7 uM, inhibits tyrosine phosphorylation of STAT3 with selectivity over STAT5 and STAT1 in cell-based assays.

A potent, selective STAT3 SH2 domain inhibitor (EC50=5.6 uM) that reduces STAT3 phosphorylation and nuclear transactivation.

A potent, selective TAAR1 agonist with Ki of 1.9, 2.7, 31 and 24 nM for mouse, rat, cynomolgus monkey and human TAAR1 stably expressed in HEK293 cells.

A potent, selective TAK1 inhibitor with IC50 of 8 nM, displays >33-fold and >62-fold selectivity over MEKK1 and MEKK4 respectively.

A potent, selective thrombopoietin (TPO) receptor agonist..

A potent, selective TLR9 antagonist with IC50 of 13 nM (human TLR9), displays 75-fold selectivity over TLR7 and no activity against TLR8 (IC50>10 uM).

A potent, selective transcriptional CDK inhibitor with Ki of 2.3 and 0.38 nM for CDK7 and CDK9, respectively.

A potent, selective translocator protein 18 kDa (TSPO/PBR) agonist with IC50 of 2.59 and 1.03 nM in competing with [3H]-PK11195 for binding to membrane preparations from rat cerebral cortex and ovary, respectively.

A potent, selective TRPC6 channel inhibitor with IC50 of 0.1-0.6 uM, 12- and 5-fold selectivity over related TRPC3 and TRPC7.

A potent, selective TRPM8 agonist with EC50 of 12 uM, a cooling agent.

A potent, selective ubiquitin-specific protease USP8 inhibitor with IC50 of 0.28 uM.

A potent, selective ubiquitin-specific protease USP8 inhibitor with IC50 of 0.56 uM.

A potent, selective ubiquitin-specific protease USP8 inhibitor with IC50 of 0.85 uM.