Rat C53 peptide (C53, pGC-B activator C53) is a novel potent, selective particulate guanylyl cyclase B (pGC-B) activator, activates pGC-B/cGMP signaling pathway, and enhances cGMP generating actions.C53 is highly resistant to NEP degradation and has less interaction with NPRC compared to CNP in vitro.C53 activates the protective pGC-B/cGMP signaling pathway and possesses enhanced cGMP generating actions.C53 inhibits fibroblast proliferation chronically and suppresses the differentiation of fibroblasts to myofibroblasts.

Ral inhibitor 1 is a covalent inhibitor of RalB (Ras-like GTPase) activation, inhibits guanine exchange factor Rgl2-mediated nucleotide exchange of Ral GTPase, selectively inhibits Ral over Ras; Ral inhibitor 1 inhibits RalB/Rgl2 interaction through covalent reaction at Tyr-82 with IC50 of 49.5 uM; Ral (Ras-like) GTPases are directly activated by oncogenic Ras GTPases.

R995045 is a novel δ-opioid receptor (δOR) agonist with pKi of 5.94, cAMP pIC50 of 6.01, >10-fold selectivity over µOR and κOR.R995045 acts as a negative allosteric modulator for leu-enkephalin potency in the cAMP glosensor assay.

QZN 34 is a small molecule pseudomonas aeruginosa PQS quorum-sensing system (PqsR) inhibitor with IC50 of 15 uM, kills planktonic Gram-positives (S. aureus, MIC 6.25 uM) but not Gram-negatives.QZN 34 prevented S. aureus biofilm formation, severely damaged established S. aureus biofilms, and perturbed P. aeruginosa biofilm development.QZN 34 killed planktonic Gram-positive pathogens including S. aureus, Staphylococcus epidermidis, Streptococcus pyogenes, and Clostridioides difficile but not Gram-negative bacteria such as P. aeruginosa and Escherichia. coli.QZN 34 eradicated the mixed-species biofilm against mixed S. aureus and P. aeruginosa biofilms when combined with aminoglycoside.

Quabodepistat (OPC-167832) is a highly potent antituberculosis agent with MIC of 0.00024 to 0.002 ug/mL against Mycobacterium tuberculosis, targets DprE1 (IC50=258 nM, recombinant DprE1), an essential enzyme for cell wall biosynthesis.OPC-167832 showed MIC90 of 0.0048 and 0.0027 ug/mL against intracellular M. tuberculosis strains H37Rv and Kurono were 0.0048 and 0.0027, respectively.OPC-167832 showed potent bactericidal activities starting at a dose of 0.625 mg/kg of body weight in a mouse model of chronic TB.OPC-167832 exhibited significant combination effects in 2-drug combinations with delamanid, bedaquiline, or levofloxacin.

PZ-1361 is a potent and selective 5-HT7 receptor antagonist with Ki of 33 nM, exhibit significant in vivo antidepressant and pro-cognitive properties in rodents.

PTG-0861 (JG-265) is a novel potent, selective HDAC6 inhibitor with IC50 of 5.92 nM, >36-fold selectivity over other HDACs.PTG-0861 (JG-265) displays HDAC6 cellular target engagement with EC50 of 0.59 uM (ELISA), has in vitro and cellular selectivity superior to HDAC6-selective inhibitor citarinostat (ACY-241).PTG-0861 (JG-265) demonstrates potency against several blood cancer cell lines (e.g. MV4-11, MM1S), whilst showing limited cytotoxicity against non-malignant cells and CD-1 mice.PTG-0861 (JG-265) exihibits promising in vitro pharmacokinetics achieved with good safety profile in cells and in vivo.

PTC-847 (PTC847) is a novel orally active inhibitor that exhibits a narrow spectrum of activity against Neisseria gonorrhoeae (N. gonorrhoeae, Ng) including MDR isolates (MIC, 0.05 to 0.1 ug/mL), directly inhibits class Ia ribonucleotide reductase (RNR).PTC-847 is inactive against the panel of Gram-negative pathogens and normal gut organism (MICs ranging from 12.5 to ≥62.5 ug/mL).PTC-847 demonstrates clear antibiotic activity preference toward all Neisseria species examined including MDR organisms and the Nm M2092 serogroup B (NMSB) reference strain.PTC-847 targets DNA synthesis and the class Ia RNR large subunit, but not DNA topoisomerases. PTC-847 showed 93% inhibition aginst Ng RNR activity at 4 uM, also inhibits Ec RNR, but does not inhibits human RNR at 100 uM.

PTC-672 (PTC672) is a novel orally active inhibitor that exhibits a narrow spectrum of activity against Neisseria gonorrhoeae (N. gonorrhoeae, Ng) including MDR isolates (MIC, 0.05 to 0.4 ug/mL), directly inhibits class Ia ribonucleotide reductase (RNR).PTC-672 is inactive against the panel of Gram-negative pathogens and normal gut organism (MICs ranging from 12.5 to ≥62.5 ug/mL).PTC-672 demonstrates clear antibiotic activity preference toward all Neisseria species examined including MDR organisms and the Nm M2092 serogroup B (NMSB) reference strain.PTC-672 targets DNA synthesis and the class Ia RNR large subunit, but not DNA topoisomerases. PTC-672 showed 78% inhibition at 2.5 μM aginst Ng RNR activity, also inhibits Ec RNR, but does not inhibits human RNR at 100 uM.PTC-672 (30 mg/kg) demosntrates in vivo efficacy in a mouse model of gonorrhea.

PST-3 (Microtubule inhibitor PST-3) is a novel microtubule inhibitor exhibited broad-spectrum cellular cytotoxicity and in vivo potency with high safety.PST-3 inhibits different cancer cell with high safety (BT549 IC50=15 uM, MDA-MB-468 IC50=16 uM), inhibits human breast cancer cell clonogenic growth with IC50 values rang from 3 uM to 25 uM (MDA-MB-231 cell IC50=11.43 uM).PST-3 binds to the colchicine binding site on microtubule, induces morphological changes, disrupts the structure of microtubule in cells and inhibits tubulin polymerization, arrests BT549 and MDA-MB-468 cells in G2/M phase.PST-3 shows preferential growth inhibition in triple-negative breast cancer xenografts growth without neurotoxicity in vivo.

PSB-17365 is a potent, selective, Gi-biased agonist of GPR84 with EC50 of 2.5 nM, β-arrestin IC50 of 104 nM in human GPR84-expressing cells.

PSB-1584 is a potent, selective agonist of GPR84 with EC50 of 5.0 nM, β-arrestin IC50 of 3.2 nM in human GPR84-expressing cells.

Psalmotoxin 1 (PCTX1) is a potent and selective acid-sensing ion channel 1a (ASIC1a) blocker with IC50 of 0.9 nM.Psalmotoxin 1 displays no effect at ASIC1b, ASIC2a, ASIC3, heteromeric ASIC channels, ENaC and KV2.1/2.2/4.2/4.3 channels expressed in oocytes at 100 nM.Psalmotoxin 1 exhibits potent analgesic properties against thermal, mechanical, chemical, inflammatory and neuropathic pain in rodents.

Procaspase-6 inhibitor 13 is a small molecule, noncovalent, allosteric inhibitor of procaspase-6 with KD of 0.38 uM.Procaspase-6 inhibitor 13 binds to pro-C6 at the dimer interface and contacts amino acids Y198, T199 and E214.Procaspase-6 inhibitor 13 significantly stabilizes procaspase-6.

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.