BAY-678 racemate is a racemate of BAY-678. BAY-678 is an orally bioavailable, highly potent, selective and cell-permeable inhibitor of human neutrophil elastase (HNE), with an IC50 of 20 nM. BAY-678 is also nominated as a chemical probe to the public via the Structural Genomics Consortium (SGC).
FGTI-2734 is a RAS C-terminal mimetic dual farnesyl transferase (FT) and geranylgeranyl transferase-1 (GGT) inhibitor with IC50s of 250 nM and 520 nM for FT and GGT, respectively. FGTI-2734 can prevent membrane localization of KRAS, hence solving KRAS resistance problem and thwarting mutant KRAS patient-derived pancreatic tumors[1].
Dabigatran(BIB-953; BIBR 953ZW) is a reversible and selective, direct thrombin inhibitor (DTI) with Ki value of 4.5 nM.IC50 Value: 4.5 nM (Ki); 10 nM(Thrombin-induced platelet aggregation) [1]Target: thrombinin vitro: Dabigatran selectively and reversibly inhibited human thrombin(Ki: 4.5 nM) as well as thrombin-induced platelet aggregation (IC(50): 10 nM), while showing no inhibitory effect on other platelet-stimulating agents.Thrombin generation in platelet-poor plasma (PPP), measured as the endogenous thrombin potential (ETP) was inhibited concentration-dependently (IC(50): 0.56 microM). Dabigatran demonstrated concentration-dependent anticoagulant effects in various species in vitro, doubling the activated partial thromboplastin time (aPTT), prothrombin time (PT) and ecarin clotting time (ECT) in human PPP at concentrations of 0.23, 0.83 and 0.18 microM, respectively [1]. in vivo: Dabigatran prolonged the aPTT dose-dependently after intravenous administration in rats (0.3, 1 and 3 mg/kg) and rhesus monkeys (0.15, 0.3 and 0.6 mg/kg). Dose- and time-dependent anticoagulant effects were observed with dabigatran etexilate administered orally to conscious rats (10, 20 and 50 mg/kg) or rhesus monkeys (1, 2.5 or 5 mg/kg), with maximum effects observed between 30 and 120 min after administration, respectively [1]. Patients treated with dabigatran etexilate experienced fewer ischaemic strokes (3.74 dabigatran etexilate vs 3.97 warfarin) and fewer combined intracranial haemorrhages and haemorrhagic strokes (0.43 dabigatran etexilate vs 0.99 warfarin) per 100 patient-years [2].Clinical trial: An Evaluation of the Pharmacokinetics and Pharmacodynamics of Oral Dabigatran Etexilate in Hemodialysis Patients . Phase1
U27391 is a metalloproteinase inhibitor. U27391 inhibits rhIL-1β Induced proteoglycan loss[1].
BMS-214662 is a potent and selective farnesyl transferase inhibitor with potent antitumor activity with an IC50 of 1.35 nM.
Feprazone (DA2370; Prenazone), an analogue of Phenylbutazone (HY-B0230), is a nonsteroidal anti-inflammatory agent with analgesic and antipyretic activities. Feprazone acts by inhibiting the activity of cyclooxygenase (COX)-2. Feprazone ameliorates free fatty acid (FFA)-induced oxidative stress by reducing the production of mitochondrial reactive oxygen species (ROS). Feprazone can decrease the expression of MMP-2 and MMP-9. Besides, Feprazone can suppress adipogenesis and increase lipolysis in differentiating 3 T3-L1 cells. Feprazone also can be used to research atherosclerosis and obesity[1][2][3].
12-O-Methylcarnosic acid (12-Methoxycarnosic acid), a diterpene carnosic acid isolated from the acetone extract of Salvia microphylla, is an active constituent of 5α-reductase inhibition with an IC50 value of 61.7 μM. 12-O-Methylcarnosic acid inhibits proliferation in LNCaP cells. 12-O-Methylcarnosic acid has antioxidant, anti-cancer and antimicrobial activity[1][2].
OBAA is a potent phospholipase A2 (PLA2) inhibitor with an IC50 of 70 nM. OBAA blocks Melittin-induced Ca2+ influx in Trypanosoma brucei with an IC50 of 0.4 μM[1][2][3].
Lorundrostat is a aldosterone synthase inhibitor[1].
Flavokawain 1i (DiNap) is an Hsp90 inhibitor. Flavokawain 1i (DiNap) has anti-cell proliferation activity and can be used in cancer research[1].
Lonafarnib is an orally bioavailable farnesyl protein transferase (FPTase) inhibitor for H-ras, K-ras and N-ras with IC50 of 1.9 nM, 5.2 nM and 2.8 nM, respectively.
MSI-1436 is a selective, non-competitive inhibitor of the enzyme protein tyrosine phosphatase 1B (PTB-1B), with an IC50 of appr 1 μM, 200-fold preference over TC-PTP (IC50, 224 μM).
Isosilybin (Isosilybinin) is a flavonoid from milk thistle; inhibits CYP3A4 induction with an IC50 of 74 μM.
Nefazodone is an orally active phenylpiperazine antidepressant. Nefazodone can potently and selectively block postsynaptic 5-HT2A receptors, and moderately inhibit 5-HT and noradrenaline reuptake. Nefazodone can also relieve the adverse effects of stress on the the immune system of mice. Nefazodone has a high affinity for CYP3A4 isoenzyme, which indicates that it has certain risk of drug-drug interaction[1][2][3].
Rosiptor is an activator of SH2-containing inositol-5'-phosphatase 1 (SHIP1).
Resorufin methyl ether (Methoxyresorufin) is a cytochrome P450 fluorometric substrate[1]. Resorufin methyl ether is a relatively specific substrate for CYP1A2 activity in rodents[1][2].
Avanafil(TA-1790) is a potent and highly selective phosphodiesterase-5(PDE-5) inhibitor(IC50=5.2 nM) for erectile dysfunction; lower selectivity against PDE1, PDE6, and PDE11.IC50 value: 5.2 nM [1]Target: PDE5Avanafil is highly selective toward PDE5 and against all other PDE isozymes tested. Lower selectivity against PDE1, PDE6, and PDE11 is consistent with results from randomized, placebo-controlled, phase 3 trials in which musculoskeletal and hemodynamic adverse events were reported in <2% of patients and no color vision-related abnormalities were reported with avanafil doses up to 200mg once daily [2]. Intraduodenal doses of avanafil or sildenafil (0.1 and 1 mg/kg) potentiated the AUC of nitroglycerin induced hypotension. However, the potentiating effect of avanafil at 1 mg/kg was significantly weaker than that of sildenafil (p <0.05) [3].
HIV-1 protease-IN-12 (compound 35b) is a HIV-1 protease inhibitor with an IC50 of 0.51 nM. HIV-1 protease-IN-12 also inhibits drug-resistant variant[1].
hACC2-IN-1 is a potent acetyl-CoA carboxylase 2 (ACC2) inhibitor, with an IC50 value of 2.5 μM (hACC2). hACC2-IN-1 could be used for obesity research[1].
MMPI-1154 is a small molecule MMP-2 inhibitor with IC50 of 10/6.6/13/1.8 uM for MMP1/2/9/13, respectively; shows significant cardio-cytoprotecion, significantly decreases infarct size when applied at 1 μM in an ex vivo model for acute myocardial infarction.
KC7F2 is a potent HIF-1 pathway inhibitor and that its potential as a cancer therapy agent warrants further study.Target：HIFin vitro: KC7F2 is the second HIF-1α inhibitor. KC7F2 is shown to inhibit the proliferation of cancer cells, an effect that is increased in hypoxia, while non-tumor cells are less sensitive. KC7F2 decreases HIF-1α levels by downregulating HIF-1α protein synthesis. [2] KC7F2 markedly inhibits HIF-mediated transcription in cells derived from different tumor types, including glioma, breast and prostate cancers and exhibited enhanced cytotoxicity under hypoxia. KC7F2 prevents the activation of HIF-target genes such as Carbonic Anhydrase IX, Matrix Metalloproteinase 2 (MMP2), Endothelin 1 and Enolase 1. KC7F2 works through the down-regulation of HIF-1α protein synthesis, an effect accompanied by the suppression of the phosphorylation of eukaryotic translation initiation factor 4E binding protein 1 (4EBP1) and p70 S6 kinase (S6K), key regulators of HIF-1α protein synthesis.[1]
MY-5445 is a specific phosphodiesterase type 5 (PDE5) inhibitor[1].
CMI977 is a potent 5-Lipoxygenase (5-LO) inhibitor.
IDO5L is a potent indoleamine 2,3-dioxygenase (IDO) inhibitor with an IC50 of 67 nM.
Sildenafil-d3 is deuterium labeled Sildenafil-d3. Sildenafil (UK-92480) is a potent phosphodiesterase type 5 (PDE5) inhibitor with an IC50 of 5.22 nM.
Otamixaban (FXV673) is a potent, selective, rapid-acting, competitive, and reversible fXa inhibitor (Ki=0.5 nM) that effectively inhibits both free and prothrombinase-bound fXa[1].
RORγt agonist 3 is a potent agonist of RORγt. RORγt agonist 3 promotes the differentiation of Th17 cells and enhances the levels of pro-inflammatory cytokines, thereby increasing the cytotoxicity of lymphocytes. RORγt agonist 3 inhibits the production of regulatory T cells, which suppresses the immune response (extracted from patent WO2021136326A1, compound 23)[1].
Xanthine oxidase-IN-8 (Icarisids J) (Compound 7) is a XOD inhibitor with an IC50 of 29.71 μM[1].
PQ-10 is a potent inhibitor of Phosphodiesterase 10A (PDE10A) with IC50 andED50 of 4.6 nM and 13 mg/kg, respectively. PQ-10 induces patterns of brain glucose metabolism which can be a potential translational biomarker. PQ-10 has the potential for researching psychiatric disorders like schizophrenia[1].
Sacubitril sodium is a potent and orally active NEP (neprilysin) inhibitor, with an IC50 of 5 nM. Sacubitril sodium enhances the tone of the natriuretic peptide (NP) system and exerts significant antihypertensive effects. Sacubitril sodium is a component of the heart failure medicine LCZ696. Sacubitril sodium can be used for the research of heart failure, hypertension and COVID-19[1][2][3].