SBI-0797750 (SBI 0797750) is a potent, fully selective PfGluPho inhibitor with robust nanomolar activity against recombinant PfGluPho, PvG6PD, and P. falciparum blood-stage parasites.SBI-0797750 disturbs the cytosolic glutathione-dependent redox potential, as well as the cytosolic and mitochondrial H2O2 homeostasis of P. falciparum blood stages, at low nanomolar concentrations.SBI-0797750 does not harm red blood cell (RBC) integrity and phagocytosis and thus does not promote anemia.

SBI-0637142 is a potent Smac mimetic that preferentially targets BIRC2, latency-reversing agent (LRA), specifically and potently promote HIV-1 latency reversal activity.SBI-0637142 modestly induced HIV-1 latency ex vivo in CD4+ T cells from ART-suppressed aviremic HIV-infected patients as a single agent, showed robust activity when administered in combination with the HDACi panobinostat.SBI-0637142's latency reversal activity is dependent on the NIK-dependent NF-κB signaling.

S2C3 is a small molecule HIV-1 fusion inhibitor, targets the membrane proximal external region (MPER) of HIV-1 envelope spike.S2C3 interacted with gp41-inter with an affinity of 2.0 uM.S2C3 has been shown to effectively block binding to the intact HIV-1 Env expressed on the cell surface by soluble CD4 but not by CD4 binding the sitedirected NAb VRC01, or the prefusion conformation-specific NAb PG16.S2C3 targets a site in the HIV-1 Env distinct from sites targeted by small-molecule entry inhibitors that have been identified so far.S2C3 could stabilize HIV-1 Env in the prefusion conformation, making it potentially useful in a vaccine preparation to reduce the conformational flexibility of Env.

S1g-2 (Hsp70-Bim inhibitor S1g-2) is a selective inhibitor to block interactions of Hsp70-Bim with IC50 of 0.4 uM in FPA assays, > 40-fold selectivity to target Hsp70-Bim over Bcl-2-Bim. S1g-2 induces cell-type-specific apoptosis in CML cells through selectively disrupting the Hsp70-Bim PPI. S1g-2 progressively enhanced lethality along with the increase in BCR-ABL-independent TKI resistance in the K562 cell lines. S1g-2 is more effective in primary samples from BCR-ABL-independent TKI-resistant patients than those from TKI-sensitive patients.

RTICBM-74 is a potent, selective, brain-penetrant CB1 negative allosteric modulator (NAM) with IC50 of 23 nM in Ca2+ assays.RTICBM-74 displays excellent half-life and low clearance against rat liver microsomes and hepatocytes, and excellent brain penetrance in rats.RTICBM-74 specifically reduces alcohol intake across a range of doses in male or female Wistar or Long-Evans rats, reduces alcohol intake and does not affect locomotion or sucrose self-administration.

RTICBM-229 is a potent, selective, brain-penetrant CB1 negative allosteric modulator (NAM) with IC50 of 169 nM in Ca2+ assay, 40 nM in GTPγS assay.

RS-1748 is a highly potent, selective, orallu active CCR4 antagonist, inhibits [125I]CCL17 binding to human CCR4 with IC50 of 59.9 nM.RS-1748 displays no competitive displacement in the binding of [125I]CCL3 (MIP-1α) to CCR1 and [125I]CCL2 (MCP-1) to CCR2b. dose-dependently inhibited 50 nM CCL22-induced [Ca2+]i mobilization with IC50 of 28.3 nM, inhibited the binding of [35S]GTPgS to human CCR4-expressing CHO cells with IC50 of 18.4 nM.Orally administered RS-1748 (30 mg/kg) significantly lowered the total cell numbers and the eosinophils numbers in ovalbumin-sensitized guinea pigs.

RS-1269 is a highly potent, selective CCR4 antagonist, inhibits [125I]CCL17 binding to human CCR4 with IC50 of 27.7 nM.RS-1269 also has strong affinity to displace the CCL17 binding with IC50 of 27.0 nM in CCR4-expressing CHO cells.RS-1269 displays no competitive displacement in the binding of [125I]CCL3 (MIP-1α) to CCR1 and [125I]CCL2 (MCP-1) to CCR2b.RS-1269 dose-dependently inhibited CCL17-induced migration of Th2 cells with IC50 of 5.5 nM.Orally administered RS-1269 (30 mg/kg) ameliorates ovalbumin-induced ear swelling in mice.RS-1269 also inhibited LPS-induced TNF-α production in vivo.

RP12146 (RP12146) is a novel, selective, and potent small molecule inhibitor of PARP1/2 with IC50 of 0.6/0.5 nM, with several fold selectivity over other isoforms.RP12146 inhibited cell growth in both BRCA mutant and non-BRCA mutant cancer cell lines with a GI50 range of 0.043 to 19.83 µM in a dose dependent manner.RP12146 demonstrated anti-tumor activities in both tumor size and tumor weight in OVCAR3 xenograft model.

Rohinitib is a potent and specific inhibitor of eIF4A1, inhibits growth and survival of AML cells especially cells with FLT3-ITD.

RO 5459072 (RG-7625) is a potent, highly selective of cathepsin S with IC50 of 0.1 nM and 0.3 nM for human and murine Cathepsin S, respectively; shows no sub-micro molar inhibition against others cathepsins (Cat L, B, K, and F) with the exception of Cat V (IC50=700  nM); dose-dependently reverses aberrant systemic autoimmunity, e.g. plasma cytokines, activation of myeloid cells and hypergammaglobulinemia, especially suppresses IgG autoantibody production.

RJR-2403 (Rivanicline, Metanicotine) is a potent, selective neuronal nicotinic ACh (nAChR) agonist with high affinity to rat brain cortex (Ki=26 nM), does not significantly activate muscle type nAChRs or muscarinic receptors; RJR-2403 is comparable to nicotine in activating rat thalamic synaptosomes with EC50 of 732 nM; significantly improves passive avoidance retention after scopolamine-induced amnesia and enhanced both working and reference memory in rats, also demonstrates greatly reduced cardiovascular effects; exerts its antinociceptive effect via nicotinic rather than either opioid or muscarinic mechanisms.

RGM8-51 is a β-lactam derivative, potent, selective TRPM8 antagonist with IC50 of 1.06 and 1.74 uM for rat and human TRPM8, respectively.RGM8-51 does not have any ability to activate TRPM8 channels, but produces a concentration-dependent inhibition of menthol activation.RGM8-51 is selective for cold-activated TRPM8 channels, displays no agonist or antagonist profile in cool-activated TRPA1 channels and has negligible activity as TRPV3 and ASIC3 channel antagonists.RGM8-51 (1 µM) inhibited menthol-activated currents in rTRPM8-expressing HEK293 cells.RGM8-51 exhibits in vivo antinociceptive activity in response to cold, in a mouse model of oxaliplatin-induced peripheral neuropathy.RGM8-51 reduces cold, mechanical and heat hypersensitivity in a rat model of neuropathic pain arising after chronic constriction of the sciatic nerve.RGM8-51 exhibits mechanical hypersensitivity-relieving activity, in a mouse model of NTG-induced hyperesthesia.

RGM079 (RGM-079) is a potent, selective α7 nAChR positive allosteric modulator (PAM) with EC50 of 8.3 uM.RGM079 exhibited a balanced pharmacokinetic profile and antioxidant properties comparable or even higher than well-known natural polyphenols.RGM079 shows neuroprotective properties in Alzheimer's disease (AD)-toxicity related models.RGM079 causes a concentration-dependent neuroprotective effect against the toxicity induced by okadaic acid (OA) in the human neuroblastoma cell line SH-SY5Y.RGM079 is able to restore the cellular viability after exposure to OA and amyloid peptide Aβ1–42, with cell death almost completely prevented at 10 and 30 μM, respectively, in primary cultures of rat cortical neurons;RGM079 shows in vivo analgesic activity in the complete CFA-induced paw inflammation model after intraperitoneal administration.

Rencofilstat (CRV431) is a non-immunosuppressive analogue of cyclosporine A and pan-cyclophilin inhibitor, potently inhibits cyclophilin isoforms A, B, D, and G with IC50 of 1-7 nM.Rencofilstat (CRV431) is more than 13 times more potent than the parent compound, cyclosporine A (CsA).Rencofilstat (CRV431) inhibits liver HBV DNA and HBsAg, reduces liver HBV DNA levels and moderately decreased serum HBsAg levels in HBV transgenic mouse model.Rencofilstat (CRV431) shows potential as a drug candidate for chronic liver diseases.

Rebimastat (BMS-275291, D2163) is a potent, broad spectrum matrix metalloproteinase (MMPs) inhibitor with potential antineoplastic activity, shows nM potency against MMP-1/2/7/9/14.BMS-275291 inhibits tumor growth in a B16BL6 model of experimental metastasis, BMS-275291 treatment results in a dose-dependent reduction in the number of lung metastases.BMS-275291 also inhibits angiogenesis in a murine angiogenesis model with a dose-dependent inhibition of endothelial cell migration.Rebimastat (BMS-275291) induces extracellular matrix degradation, and inhibiting angiogenesis, tumor growth and invasion, and metastasis.

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.