A potent, selective p38α MAPK inhibitor with IC50 of 9 nM.

A potent, selective PDE3 inhibitor with IC50 of 36 nM, displays >20,000-fold selectivity over PDE1..

A potent, selective PDE3 inhibitor with IC50 of 50 nM.

A potent, selective peptide inhibitor of hERG channel with IC50 of 3.3 nM for hERG1 channels.

A potent, selective phosphodiesterase 4 (PDE4) inhibitor with IC50 of 26.1, 22.8, 21 and 0.28 nM for PDE4A4, PDE4B2, PDE4C2 and PDE4D3, respectively..

A potent, selective PLK1 PBD inhibitor with IC50 of 1.36 uM.

A potent, selective presynaptic dopamine autoreceptor antagonist.

A potent, selective protein tyrosine phosphatase DUSP5, PTP1B and SHP-2 inhibitor with IC50 of 36 uM, 2.1 and 1.1 uM respectively, 8-fold selectivity for PTP1B versus DUSP5.

A potent, selective RARα agonist.

A potent, selective RARβ antagonist that inhibits RA-induced transcriptional activation of RARβ, but not RARα, RARγ or RXRα on a variety of RA response elements.

A potent, selective receptor interacting protein-2 (RIP2) kinase inhibitor..

A potent, selective renal outer medullary potassium channel (ROMK, Kir1.1) inhibitor with IC50 of 0.24 uM in T1+ flux assays.

A potent, selective S1P1 receptor full agonist with EC50 of 13.8 nM, with no activites at the S1P2-5 receptors.

A potent, selective S1P3 antagonist with Ki of 0.25 nM.

A potent, selective S1P3 antagonist with Ki of 0.25 nM.

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.