SHP836 is a distinct, allosteric site 2 SHP2 inhibitor with IC50 of 12 uM (SHP2 1-525), and selective over the phosphatase domain (SHP2 PTP IC50>100 uM).downregulates DUSP6 mRNA, a downstream MAPK pathway marker, in KYSE-520 cancer cells; enhances pharmacological pathway inhibition in cells combined with SHP099.
GYKI-47261 dihydrochloride is a competitive, orally active, and selective AMPA receptor antagonist with an IC50 of 2.5 μM. GYKI-47261 has broad spectrum anticonvulsive activity and neuroprotective effects. GYKI-47261 dihydrochloride is also a potent inducer of CYP2E1[1][2].
Calcineurin autoinhibitory peptide is a selective inhibitor of Ca2+/calmodulin-dependent protein phosphatase (calcineurin), with an IC50 of ~10 μM. Calcineurin autoinhibitory peptide could protect neurons from excitatory neuronal death[1][2].
Seviteronel (VT-464) racemate is the racemate form of Seviteronel (VT-464), which is a potent CYP17 lyase inhibitor(h-Lyase IC50=nM)inhibition.
2'-Ethyl Simvastatin (compound 6) is a Mevinolin analog, with HMG-CoA reductase inhibition[1].
GSK805 is a potent, orally bioavailable RORγγ Inhibitor with pIC50 of 8.4 and >8.2 for RORγ FRET assay and Th17 assay.
RORγt Inverse agonist 2 is a selective, orally active RORγt inverse agonist with an EC50 of 119 nM[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].
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
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:
INT-767 is a dual farnesoid X receptor/TGR5 agonist with mean EC50s of 30 and 630 nM, respectively.
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].
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.
COX/5-LO-IN-1 is an inhibitor of cylooxygenase and 5-lipoxygenase, used for the research of inflammatory and allergic disease states.
Lycopodine, a pharmacologically important bioactive component derived from Lycopodium clavatumspores, triggers apoptosis by modulating 5-lipoxygenase, and depolarizing mitochondrial membrane potential in refractory prostate cancer cells without modulating p53 activity[1]. Lycopodine inhibits proliferation of HeLa cells through induction of apoptosis via caspase-3 activation[2].
CMS-121 is a quinolone derivative and an orally active acetyl-CoA carboxylase 1 (ACC1) inhibitor. CMS-121 protects HT22 cells against ischemia and oxidative damage with EC50 values of 7 nM and 200 nM, respectively. CMS-121 has strong neuroprotective, anti-inflammatory, antioxidative and renoprotective activities[1][2][3].
(-)-PX20606 trans isomer is a FXR agonist with EC50s of 18 and 29 nM for FXR in FRET and M1H assay, respectively.
E6446 is a potent and orally acitve TLR7 and TLR9 antagonist, used in the research of deleterious inflammatory responses.
Tetrapeptide-30 is a skin-brightening peptide consisting of four amino acids. Tetrapeptide-30 can act as a tyrosinase inhibitor, lightening hyperpigmentation and evening out skin tone by reducing the amount of tyrosinase and inhibiting melanocyte activation[1].
AMG-1694 is a potent glucokinase–glucokinase regulatory protein (GK-GKRP) disruptors and promotes the dissociation of the GK-GKRP complex with an IC50 of 7 nM, indirectly increasing GK enzymatic activity. AMG-1694 potently reverses the inhibitory effect of GKRP on GK activity and promotes GK translocation. AMG-1694 normalizes blood glucose levels in several rodent models of diabetes and lowes blood glucose restricted to diabetic and not normoglycaemic animals[1].
Raltegravir is a potent integrase (IN) inhibitor, used to treat HIV infection.
Vatiquinone is a potent cellular oxidative stress protectant, which could be used to treat mitochondrial diseases.
Rentiapril racemate is the racemate of Rentiapril. Rentiapril is an angiotensin converting enzyme (ACE) inhibitor.
PDE5/HDAC-IN-1 (Compound 26) is a potent phosphodiesterase 5 (PDE5) and HDAC inhibitor with IC50 values of 46.3 nM and 14.5 nM, respectively. PDE5/HDAC-IN-1 induces cell apoptosis and shows anticancer activities[1].
Adjudin is an extensively studied male contraceptive with a superior mitochondria-inhibitory effect. Adjudin is also a potent Cl- channel blocker.
Polmacoxib (CG100649) is a first-in-class, orally active nonsteroidal anti-inflammatory drug (NSAID) which is a dual inhibitor of COX-2 (IC50 around 0.1 μg/ml) and carbonic anhydrase[1]. Polmacoxib inhibits colorectal adenoma and tumor growth in mouse models[2].
SA57 is a potent, selective FAAH inhibitor with IC50s of 3.2 nM and 1.9 nM for mouse and human FAAH. SA57 also inhibits the 2-arachidonoylglycerol hydrolases MAGL (IC50s of 410 nM and 1.4 μM for mouse and human MAGL) and mouse α/β-hydrolase domain-containing protein 6 (mABHD6; IC50 of 850 nM), but not other brain serine hydrolases[1][2].
PD 113413 is formed by subsequent hydrolysis of the diketopiperazine quinapril analog. PD 113413 is a potent angiotensin-converting enzyme inhibitor. PD 113413 can be used for research of hypertension and congestive heart failure[1].