RORγt Inverse agonist 2 is a selective, orally active RORγt inverse agonist with an EC50 of 119 nM[1].
Ilexoside O is a triterpene saponin isolated from the roots of Ilex pubescens. Ilexoside O exhibits weak xanthine oxidase (XOD) inhibitory activity (IC50=53.05 μM)[1].
(3R,5S)-Fluvastatin ((3R,5S)-XU 62-320) sodium is the 3R,5S-isomer Fluvastatin. Fluvastatin (XU 62-320 free acid) is a first fully synthetic, competitive HMG-CoA reductase inhibitor with an IC50 of 8 nM. Fluvastatin protects vascular smooth muscle cells against oxidative stress through the Nrf2-dependent antioxidant pathway[1][2][3].
Isothymusin is a potent anti-oxidant agent. Isothymusin shows radical scavenging activities. Isothymusin shows anti-proliferative activities in cancer cell lines. Isothymusin inhibited the enzymes associated with the promotion stage of cancer, including cycloxygenase- 2 and lipoxygenase-5[1][2].
Chlorzoxazone is a centrally acting muscle relaxant used to treat muscle spasm and the resulting pain or discomfort. It acts on the spinal cord by depressing reflexes.Chlorzoxazone is currently being used as a marker substrate in vitro/vivo studies to quantify cytochrome P450 2E1 (CYP2E1) activity in humans.
PTPN22-IN-1 is a potent PTPN22 inhibitor (IC50=1.4 µM; Ki=0.50 µM). PTPN22-IN-1 exhibits >7-10 fold selectivity for PTPN22 over similar phosphatases. PTPN22-IN-1 augments antitumor immune responses[1]. From WO2021007491A1 compound L-1.
BRL-50481 is a novel and selective inhibitor of PDE7 with IC50s of 0.15, 12.1, 62 and 490 μM for PDE7A, PDE7B, PDE4 and PDE3, respectively.
Mefentrifluconazole is a novel azole derivative and used as an agrochemical broad-spectrum antifungal agent. Mefentrifluconazole is a potent, selective and orally active fungal CYP51 (Kd= 0.5 nM) inhibitor, but shows less inhibitory activity on human aromatase (IC50=0.92 μM)[1].
Cathepsin L-IN-3 is a tripeptide-sized cathepsin L inhibitor.
Falcarinol (Panaxynol) is a natural, orally active Hsp90 inhibitor targeting both the N-terminal and C-terminal of Hsp90 with limited toxicities. Falcarinol (Panaxynol) induces apoptosis[1].
Hsp90-Cdc37-IN-3 (Compound 9) is a novel celastrol−imidazole derivative with anticancer activity. Hsp90-Cdc37-IN-3 inhibits Hsp90−Cdc37 by covalent-binding, and induces apoptosis[1].
Win 18446 is an orally active testes-specific enzyme ALDH1a2 inhibitor, with an IC50 of 0.3 μM. Win 18446 reversibly inhibits spermatogenesis in many species and inhibits Retinoic acid (HY-14649) biosynthesis from Retinol (HY-B1342) within the testes[1][2].
Methyl rosmarinate is a noncompetitive tyrosinase inhibitor which is isolated from Rabdosia serra, with an IC50 of 0.28 mM for mushroom tyrosinase, and also inhibits a-glucosidase[1].
PDK4-IN-1 is an anthraquinone derivative and a potent and orally active pyruvate dehydrogenase kinase 4 (PDK4) inhibitor with an IC50 value of 84 nM. PDK4-IN-1 potently represses cellular transformation and cellular proliferation and induces apoptosis. PDK4-IN-1 has antidiabetic, anticancer and anti-allergic activity[1].
Tovinontrine (IMR-687) is a highly potent and selective phosphodiesterase-9 (PDE9) inhibitor specifically for the treatment of sickle cell disease. IC50s are 8.19 nM and 9.99 nM for PDE9A1 and PDE9A2, respectively[1].
Dabigatran etexilate(BIBR-1048) is the orally active prodrug of dabigatran; Dabigatran 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]in 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
1-Linoleoyl glycerol (1-LG) is a fatty acid glycerol that has been isolated from S. chinensis roots.
Glucosamine (hydrochloride) is a natural product.IC50 value:Target:In vitro: Glucosamine hydrochloride exhibited dose-dependent DPPH antioxidant activity [1]. Short-term (4 h) glucosamine hydrochloride treatment inhibited HIF-1α at the protein level, decreased phosphorylation of p70S6K and S6, translation-related proteins [2]. In the obstructed kidneys and TGF-β1-treated renal cells, glucosamine hydrochloride significantly decreased renal expression of α-smooth muscle actin, collagen I, and fibronectin [3]. In vivo:
Calyculin A is a potent and cell-permeable protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A) inhibitor with IC50s of 0.5 to 1 nM.
7-Hydroxycoumarinyl-γ-linolenate is a cytosolic phospholipase A2 (cPLA2) fluorogenic substrate. 7-Hydroxycoumarinyl-γ-linolenate can be used to monitor the enzymatic activity of cPLA2[1].
BAY 73-6691 is a potent, selective brain penetrant PDE9A inhibitor.
INT-767 is a dual farnesoid X receptor/TGR5 agonist with mean EC50s of 30 and 630 nM, respectively.
BMS961 is a selective retinoic acid receptor-γ (RARγ) agonist. BMS961 shows anti-inflammatory activity[1].
Fipronil is an insecticide that acts as a selective antagonist of insect GABA receptors (IC50s = 30 nM and 1,600 nM for cockroach and rat receptors, respectively). Fipronil also inhibits desensitizing and non-desensitizing glutamate-induced chloride currents in cockroach neurons (IC500s = 800 nM and 10 nM, respectively). Fipronil induces activity of the cytochrome P450 (CYP) isoforms CYP1A1/2, CYP2B1/2, and CYP3A1/2 in isolated rat liver microsomes.
CETP-IN-3 (Compound 13) is an small molecule inhibitor of the plasma glycoprotein cholesterol ester transfer protein (CETP), elevating HDL-C through inhibition of CETP. CETP-IN-3 for the CETP inhibitory activity in the scintillation proximity (SPA) and whole plasma assay (WPA) with IC50s of 0.002 μM and 0.06 μM, respectively[1].
Quinaprilat is an orally active non-mercapto Angiotensin Converting Enzyme (ACE) inhibitor, the active metabolite of Quinapril. Quinaprilat specifically blocks the conversion of angiotensin I to the vasoconstrictor angiotensin II and inhibits the degradation of bradykinin. Quinaprilat acts as anti-hypertensive agent and vasodilator[1][2].
AZ876 is a novel high-affinity LXR agonist. AZ876 was 25-fold and 2.5-fold more potent than GW3965 (HY-10627) on human (h)LXRα and hLXRβ respectively.(1) AZ876 suppressed up-regulation of hypertrophy- and fibrosis-related genes, and further inhibited prohypertrophic and profibrotic transforming growth factor β (TGFβ)-Smad2/3 signalling.(2) AZ876 prevented TGFβ- and angiotensin II-induced fibroblast collagen synthesis, and inhibited up-regulation of the myofibroblastic marker, α-smooth muscle actin.(3) The reference for administration is 20 umol/kg/day in vivo.
NPD-001 is a potent Trypanosoma brucei phosphodiesterases TbrPDEB1 and TbrPDEB2 inhibitor, with IC50 values of 4 and 3 nM, respectively. NPD-001 also inhibits human PDEs (phosphodiesterases). NPD-001 shows good anti trypanosomal activity, with an IC50 of 80 nM[1].
AAA-pNA is a chromogenic substrate of Tripeptidyl-peptidase II. AAA-pNA can be used to test Tripeptidyl-peptidase II activity[1].
Veledimex S enantiomer is the S enantiomer of veledimex. Veledimex is an oral activator ligand for a proprietary gene therapy promoter system, and a moderate inhibitor of and substrate for CYP3A4/5.