Procaspase-6 inhibitor 12 is a small molecule, noncovalent, allosteric inhibitor of procaspase-6 with KD of 0.47 uM.Procaspase-6 inhibitor 12 binds to pro-C6 at the dimer interface and contacts amino acids Y198, T199 and E214.Procaspase-6 inhibitor 12 significantly stabilizes procaspase-6.Procaspase-6 inhibitor 12 prevents the activation of the Caspase-6 zymogen by mHTT1–586 in COS-7 cells.

PRC2 EED-IN-1 is a potent, selective, allosteric, orally bioavailable inhibitor of the EED subunit of histone methyltransferase PRC2 with IC50 of 44 nM (H3K27me3 inhibition).PRC2 EED-IN-1 retains efficacy against EZH2 inhibitor-resistant cell lines (Karpas 44 cell IC50=27 nM), exhibits in vivo efficacy in EZH2-driven tumors in vivo.

PRAX-562 (PRAX562) is a novel persistent sodium current (INa) inhibitor, inhibits hNaV1.6 persistent INa induced by ATX-II or SCN8A mutation N1768D with IC50 of 141 and 75 nM, respectively.PRAX-562 displays similar potency for inhibition of persistent INa expressed by other human NaV isoforms (hNaV1.1, hNaV1.2, hNaV1.5) as well as rat, dog, and mouse orthologs (rNaV1.2, dNaV1.2, mNaV1.6, rNaV1.6), with IC50 values ranging 109-180 nM.PRAX-562 exhibits tonic block with lower potency (IC50=8470 nM), demonstrating 60-fold preference for persistent INa, also exhibits preference for persistent INa over peak INa tonic block for hNaV1.1 (173-fold).PRAX-562 reduces intrinsic excitability of hippocampal CA1 pyramidal neurons without compromising action potential (AP) amplitude.PRAX-562 (3 mg/kg, po) produces dose-dependent protection (increase in latency) of mice against MES-induced tonic hindlimb seizures (EC50=90.1 ng/ml), with complete protection at 10 mg/kg.

PPARγ pSer273-IN-10 is a specific, in vivo-active small molecule inhibitor of CDK5-mediated Ser273 phosphorylation of PPARγ without classical PPARγ agonism.PPARγ pSer273-IN-10 is a potent PPARγ binder and in vitro inhibitor of the CDK5-mediated phosphorylation of PPARγ Ser273 and displays negligible PPARγ agonism in a reporter gene assay. PPARγ pSer273-IN-10 demonstrated an improvement in insulin sensitivity in the ob/ob diabetic mouse model in 7 day treatment in vivo testing.

PKUMDL-YC-1205 is a specific small molecule that can specifically bind to the disordered bHLH-LZ domain of c-Myc (SPR kd=18 uM).PKUMDL-YC-1205 abrogates cell proliferation of HL-60 cells with IC50 of 40 uM, blocks the interaction between c-Myc370–409 and Max.

PKM-833 (PKM833) is a potent, selective, and orally active FAAH inhibitor with IC50 of 8.8 and 10 nM against human and rat FAAH, respectively.PKM‐833 showed human and rat K inact/K i values with 34 300 ± 10 800 and 128 000 ± 39 800 mol-1 L−1 s-1, respectively.PKM-833 does not inhibit human MAGL and a panel of 137 molecular targets, exhibits weak inhibitory effects (>50%) in five receptor binding assays [PFA, 5‐HT2B, sigma, Na+ channel and Cl‐ channel (GABA gated) at 20 uM.PKM-833 showed excellent brain penetration and good oral bioavailability, and elevated anandamide (AEA) concentrations in the rat brain.PKM-833 significantly attenuated formalin-induced pain responses (3 mg/kg) and improved mechanical allodynia in CFA-induced inflammatory pain (0.3-3 mg/kg) in rat models, without significant side effects on catalepsy and motor coordination up to 30 mg/kg.

PKCθ inhibitor 22 is a potent, selective, orally bioavailable inhibitor of Protein Kinase Cθ (PKCθ) with IC50 of 6 nM.PKCθ inhibitor 22 inhibits IL-2 release from PBMCs following stimulation with anti-CD3/CD28 (IC50=0.19 uM).PKCθ inhibitor 22 also inhibits the release of IL-17 from CD3/CD28 stimulated Th-17 cells with an IC50 of 1 uM.PKCθ inhibitor 22 demonstrated a reduction of symptoms in a mouse model of multiple sclerosis.

Pipinib is a small molecule Hedgehog signaling inhibitior by selective inhibition of phosphatidylinositol 4-kinase IIIβ (PI4KB, IC50=2.2 uM), inhibits Purmorphamine-induced osteogenesis with IC50 of 0.6 uM.Pipinib inhibited GLI reporter gene activity in Sonic hedgehog (Shh)-LIGHT2 cells (IC50=1.7 uM) and expression of Hh target genes Ptch1 and Gli1 (IC50=3.1 uM and 4.1 uM, respectively).Pipinib does not modulate Hh signaling via SMO.Pipinib is an ATP-competitive inhibitor of PI4KB activity, does not inhibit isoenzymes PI4KA, PI4K2A or PI4K2B up to 50 uM.Pipinib suppresses GLI-mediated transcription and Hh target gene expression by impairing SMO translocation to the cilium.

PHT-7.3 (Cnksr1 (Cnk1) inhibitor PHT-7.3) is a selective inhibitor of connector enhancer of kinase suppressor of Ras 1 (Cnk1) pleckstrin homology (PH) domain (Kd=4.7 μM).PHT-7.3 bound selectively to the PH domain of Cnk1, preventing plasma membrane colocalization with mut-KRas.PHT-7.3 inhibits mut-KRas, but not wild-type KRas cancer cell and tumor growth and signaling.

PG3d (Caspase-6 inhibitor PG3d) is a cell-active, allosteric and irreversible, non-competitive Caspase-6 inhibitor.PG3d preferentially inhibits the cleavage of protein over peptide substrates both with purified proteins and in live cells.PG3d prevents the C6 (Caspase-6)-HTT interaction and prevents mHTT1-586 mediated activation of procaspase-6.PG3d specifically inhibits the cleavage of protein, but not peptide substrates of Caspase-6.

PG-116800 is a selective, oral matrix metalloproteinase (MMPs) inhibitor with significant antiremodeling effects in animal models of MI and ischemic heart failure.

PFI-5 a highly biochemically potent, selective, and cell-active SMYD2 chemical probe with IC50 of 8 nM.PFI-5 inhibits p53 methylation in MCF7 cells with EC50 of 1.3 uM, with no toxicity.

PF-2771 is a potent, selective CENP-E inhibitor with IC50 of 16.1 nM; does not inhibit the ATPase activities of highly related kinesins (Eg5/KSP, chromokinesin and MCAK, IC50> 1 uM); selectively inhibits proliferation of basal breast cancer cell lines; regresses tumor growth correlated with increased phospho-HH3-Ser10 levels in a breast cancer xenograft tumor model.

PF-07284892 (PF 07284892) is a small molecule inhibitor of SHP2 that may block MAPK signaling and lead to tumor growth inhibition.

PF-07284890 (ARRY-461) is an orally bioavailable, brain penetrant, potent, small molecule BRAF V600 mutants inhibitor, inhibits BRAF and CRAF with IC50 of 5.8 and 4.1 nM, respectively.PF-07284890 inhibits the clinically relevant kinase domain BRAF V600 mutants (V600E and V600K) with IC50 of 24-25 nM.PF-07284890 potently inhibits phosphorylation of ERK, a downstream marker of BRAF inhibition, and potently inhibits proliferation of BRAF V600E/K mutant melanoma cell lines (IC50=18-38 nM).PF-07284890 inhibits phosphorylation of ERK in A375 BRAF V600E tumors, achieving maximal target inhibitions at a dose of 10 mg/kg.PF-07284890 (10-30 mg/kg BID) caused significant and durable tumor regressions in the intracranial A375-luc BRAF V600E melanoma xenograft model.

PF-07265807 (PF 07265807) is a potent, selective dual Axl/Mer inhibitor, blocks Axl- and Mer-mediated signal transduction pathways, and inhibits proliferation and migration of Axl- and Mer-overexpressing tumor cells.

PF-06952229 is a potent, selective and orally active TGFbR1 inhibitor, specifically binds to TGFbR1 and prevents TGFbR1-mediated signal transduction, shows with potential antineoplastic activity.

PF-06842874 is a potent, selective CDK4/6 inhibitor.

PF-06669571 (PF 6669571) is a novel dopamine D1 receptor (D1R) partial agonist with Ki of 10 nM, demonstrates efficacy in pre-clinical models of Parkinson’s disease symptoms.

PF-06526290 is a potent, selective Nav1.3 inhibitor with IC50 of 5.1 uM, interact with the Domain 4 voltage sensor domain (D4 VSD and shows no activity for Nav1.7.

PF-06427878 is a potent, selective, oral DGAT2 inhibitor with IC50 of 99/202 nM for human/rat DGAT2, >470-fold selectivity over DGAT1 and MGAT1/2/3.PF-06427878 inhibits DGAT2-dependent triglyceride (TG) synthesis in primary human hepatocytes with IC50 of 11.6 nM.PF-06427878 reduces hepatic and circulating plasma TG levels as well as lipogenic gene expression in rats maintained on a Western-type diet (0.3-30 mg/kg bid. po.).PF-06427878 significantly improves steatosis and hepatocellular ballooning with a decrease in lobular inflammation in a murine nonalcoholic steatohepatitis (NASH) model (2 or 20 mg/kg bid. po.).

PF-04827736 ((S)-PF-04677490) is a potent, selective PDE1 inhibitor with IC50 of 42, 9.1 and 38 nM for PDE1A, PDE1B and PDE1C, respectively; displays >10-fold selectivity over PDE10A1, and >45-fold selectivity over other PDE isoforms.

PD-L1 inhibitor 4 is a small molecule inhibitor of PD-1/PD-L1 with SPR KD of 0.079 nM.PD-L1 inhibitor 4 exhibited substantially increased binding affinity to hPD-L1, as well as PD-1/PD-L1 inhibitory activity in physiological conditions.PD-L1 inhibitor 4 also showed a dose-dependent increase in IFN-γ secretion levels in a mixed lymphocyte reaction assay.

PDE-I2 is a potent and selective inhibitor of malaria proliferation with Pf IC50 of 18 nM.PDE-I2 is a precursor of the anticancer duocarmycin family that preserves the class's sequence-specific DNA binding but lacks its signature DNA alkylating cyclopropyl warhead.PDE-I2 retains comparable antimalarial potency to chloroquine.PDE-I2 is >1,000-fold less toxic to human cell lines than duocarmycin, with mitigated impacts on eukaryotic chromosome stability.PDE-I2 treatment induces severe defects in parasite nuclear segregation leading to impaired daughter cell formation during schizogony.

PCH-1 is a potent antitumor agent that disrupts microtubule assembly, leading to cancer cell death, interacts vinblastine binding site on tubulin; PCH-1 exhibits the strongest cytotoxic activity through interaction with tubulin, leading to cell cycle arrest and induction of apoptosis. PCH-1 efficiently inhibits the growth of NSCLC cancer cell lines at micromolar concentrations (A-549 IC50=4.32 uM, H226 IC50=4.69 uM), and non-toxic to normal cells.

PBI-4547 is an agonist of GPR40/120 and an antagonist of GPR84, also is a partial ligand and activator of PPAR.PBI-4547 dose-dependently inhibits GPR84/Gαi2 activation (reflected by an increase in BRET signal) with IC50 of 17 uM, activates GPR40 (EC50 of 102 µM for Gαq and 16 µM for Gαi2) and dose-dependently promoted β-arrestin-2 recruitment to GPR120 (EC50=148 uM).PBI-4547 prevents progression, improves glucose metabolism in a mouse model of NAFLD, restores hepatic glucose and FA metabolism.

PARPYnD is the first cell-active photoaffinity probe (AfBP) for PARP protein class, based on triple PARP1/2/6 inhibitor AZ9482.PARPYnD is a robust tool for profiling PARP1/2 and is used to profile clinical PARP inhibitor olaparib, identifying several novel off-target proteins.PARPYnD can enrich recombinant PARP6 spiked into cellular lysates and inhibits PARP6 in cell-free assays, it does not label PARP6 in intact cells.PARPYnD inhibits PARP1/2/6 with IC50 of 38/6/230 nM, respectively.

OX2R agonist 1 is a potent, selective, small-molecule agonist of orexin receptor 2 (OX2R) with pEC50 of 8.28, >300-fold selectivity over OX1R.

OX01401 (OX-01401, OX1401) is a potent, selective and cell active inhibitor of the PIM kinase family (PIM1 IC50=15.1 nM).OX01401 inhibited proliferation of two PIM-expressing leukaemic cancer cell lines, MV4-11 (IC50=0.5 uM) and PC3 cell (IC50=1.1 uM), and to reduced intracellular phosphorylated 4EBP1 protein in a concentration dependent manner.

OR-S0 is a potent, selective EZH2 inhibitor with IC50 of 11 nM, weakly inhibitor EZH1 (IC50=91 nM).OR-S0 inhibits H3K27me3 in HCT116 cells with IC50 of 24 nM, inhibited the growth of KARPAS‐422 cells in a dose‐dependent manner with GI50 of 210 nM.