Doxazosin mesylate(UK 33274) is a quinazoline-derivative that selectively antagonizes postsynaptic α1-adrenergic receptors.Target: α1-adrenergic receptorDoxazosin (mesylate) is the mesylate salt form of doxazosin, which is a long-lasting inhibitor of α1-adrenoceptors that is widely used to treat benign prostatic hyperplasia and lower urinary tract symptoms [1]. doxazosin may have a direct inhibitory effect on cholesterol synthesis independent of the LDL receptor. The inhibition of cholesterol synthesis by doxazosin may cause cells to compensate by upregulating the LDL receptor, thereby increasing the importation of lipoprotein cholesterol and reducing LDL cholesterol in the medium [2]. Doxazosin monotherapy was effective in eight of 12 patients (66.7%), and combined therapy with a beta-blocker was effective in 11 of 12 patients (91.7%). The mean pulse rate remained constant throughout therapy. Adverse reactions were minor and transient and occurred in only three patients. Urinary and plasma catecholamine levels tended to decrease or remained unchanged during doxazosin therapy [3].
Salvianolic acid B is an active ingredient of Salvia miltiorrhiza, which has been widely applied in China for the management of various microcirculation-related disorders, such as cardiovascular disease, cerebrovascular disease, and diabetic vascular complication.IC50 value:Target:In vitro: Salvianolic acid B (SA-B) 1 and 10 micromol/L decrease the cell active TGF-beta1 secretion by 63.3 % and 15.6 % of the control, down-regulat pro-collgen alpha1(I) mRNA expression to 77.0% and 51.8% respectively (P<0.05). SA-B 1 and 10 micromol/L also inhibit MAPK activity by 1 to 2 fold respectively [3].In vivo: Salvianolic acid B (SalB) (5 mg · kg-1 · h-1) significantly attenuates LPS-induced pulmonary microcirculatory disturbance, including the increase in leukocyte adhesion and albumin leakage. In addition, LPS increases pulmonary tissue wet-to-dry weight ratio and tumor necrosis factor [alpha] and interleukin 8 levels in plasma and bronchoalveolar lavage fluid enhances the expression of E-selectin, intercellular adhesion molecule 1, myeloperoxidase, MMP-2, and MMP-9, whereas it decreases the expression of AQP-1 and AQP-5 in pulmonary tissue, all of which are attenuated by SalB pretreatment[1]. SalB administration (10 mg/kg) significantly ameliorate the Aβ25-35 peptide-induced memory impairment in the passive avoidance task (P<0.05). SalB treatment also reduced the number of activated microglia and astrocytes that are observed during the inflammatory reaction after the administration of the Aβ25-35 peptide. Moreover, SalB markedly reduce inducible nitric oxide synthase and cyclooxygenase-2 expression levels and thiobarbituric acid reactive substances, which are increased by the administration of the Aβ25-35 peptide. Furthermore, SalB administration significantly rescue the Aβ25-35 peptide-induced decrease of choline acetyltransferase and brain-derived neurotrophic factor protein levels[2].
Lapatinib-d7 (GW572016-d7) ditosylate is the deuterium labeled Lapatinib. Lapatinib (GW572016) is a potent inhibitor of the ErbB-2 and EGFR tyrosine kinase domains with IC50 values against purified EGFR and ErbB-2 of 10.2 and 9.8 nM, respectively[1][2].
Apatinib free base (YN968D1 free base) is an orally bioavailable tyrosine kinase inhibitor, which selectively targets VEGFR-2 (IC50=1 nM). Apatinib free base (YN968D1 free base) is an anti-angiogenic drug for the treatment of advanced or metastatic gastric cancer. Apatinib free base (YN968D1 free base) potently inhibits Ret, c-Kit and c-Src with IC50s of 13, 429 and 530 nM, respectively. It also inhibits cellular phosphorylation of VEGFR-2, c-kit and PDGFRβ[1][2][3].
Diazoxide-d3 is deuterium labeled Diazoxide. Diazoxide (Sch-6783) is an ATP-sensitive potassium channel activator, has the potential for hyperinsulinism treatment.
Latrepirdine dihydrochloride is a neuroactive compound with antagonist activity at histaminergic, α-adrenergic, and serotonergic receptors. Latrepirdine stimulates amyloid precursor protein (APP) catabolism and amyloid-β (Aβ) secretion.
Enzalutamide (MDV3100) is an androgen receptor (AR) antagonist with an IC50 of 36 nM in LNCaP prostate cells.
Bergapten-d3 is deuterium labeled Bergapten. Bergapten is a natural anti-inflammatory and anti-tumor agent. Bergapten is inhibitory towards mouse and human CYP isoforms.
Curcumin 5-8 (CUR5-8) is a potent and orally active naturally active curcumin (CUR) analog. Curcumin 5-8 inhibits lipid droplet formation. Curcumin 5-8 increases autophagy and inhibits Apoptosis. Curcumin 5-8 improves insulin resistance and insulin sensitivity[1].
AG-490 is a tyrosine kinase inhibitor that inhibits EGFR, Stat-3 and JAK2/3.
LY294002 is a broad-spectrum inhibitor of PI3K with IC50s of 0.5, 0.57, and 0.97 μM for PI3Kα, PI3Kδ and PI3Kβ, respectively. It also inhibits CK2 with an IC50 of 98 nM.
Tempol-d17,15N is the deuterium labeled Tempol[1]. Tempol is a general superoxide dismutase (SOD)-mimetic drug that efficiently neutralizes reactive oxygen species (ROS)[2][3].
Calcimycin hemicalcium salt (A-23187 hemicalcium salt) is an antibiotic and a unique divalent cation ionophore (like calcium and magnesium). Calcimycin hemicalcium salt induces Ca2+-dependent cell death by increasing intracellular calcium concentration. Calcimycin hemicalcium salt inhibits the growth of Gram-positive bacteria and some fungi. Calcimycin hemicalcium salt also inhibits the activity of ATPase and uncouples oxidative phosphorylation of mammalian cells. Calcimycin hemicalcium salt induces apoptosis[1][2][3][4].
Amiodarone is an antiarrhythmic drug for inhibition of ATP-sensitive potassium channel with IC50 of 19.1 μM. Target: Potassium ChannelAmiodarone shows beta blocker-like and potassium channel blocker-like actions on the SA and AV nodes, increases the refractory period via sodium- and potassium-channel effects, and slows intra-cardiac conduction of the cardiac action potential, via sodium-channel effects. Amiodarone (2-butyl, 3-(4-diethylaminoethoxy, 3,5-diiodo, benzoyl) benzofuran hydrochloride), an anti-anginal drug which causes coronary dilatation and depresses myocardial oxygen consumption, was found to protect anaesthetized guinea-pigs against ouabain-induced ventricular fibrillation.2. A 5% (73.4 mM) solution of amiodarone had no local anaesthetic action on guinea-pig skin [1]. Amiodarone proved safe in patients with severe congestive heart failure and severe myocardial damage. Its clinical efficacy was related to its electrophysiologic properties and to two unique properties: its wide safety margin and its cumulative effect [2].
Irinotecan-d10 ((+)-Irinotecan-d10) hydrochloride is the deuterium labeled Irinotecan. Irinotecan ((+)-Irinotecan) is a topoisomerase I inhibitor, preventing religation of the DNA strand by binding to topoisomerase I-DNA complex[1][2].
Niclosamide olamine is an anthelmintic that disrupts mitochondrial metabolism in parasitic worms and animal models. Niclosamide olamine inhibits STAT3 (IC50 = 0.25 μM) and stimulates autophagy by reversibly inhibiting mammalian target of Rapamycin complex 1 (mTORC1) signaling.
Clematichinenoside AR is a major active ingredient that could be extracted from the traditional Chinese herb Clematis chinensis and has potent pharmacological effects on various diseases, including atherosclerosis (AS)[1].
Dioscin(CCRIS 4123; Collettiside III) is a natural steroid saponin derived from several plants, showing potent anti-cancer effect against a variety of tumor cell lines. IC50 value:Target: Anticancer agentin vitro: dioscin (1, 2 and 4 μmol/L) could significantly inhibit the viability of LNCaP cells in a time- and concentration-dependent manner. Flow cytometry revealed that the apoptosis rate was increased after treatment of LNCaP cells with dioscin for 24 h, indicating that apoptosis was an important mechanism by which dioscin inhibited cancer [1]. dioscin abrogated AKT phosphorylation, which subsequently impaired RANKL-induced nuclear factor-kappaB (NF-κB) signaling pathway and inhibited NFATc1 transcriptional activity. Moreover, in vivo studies further verified the bone protection activity of dioscin in osteolytic animal model [2]. Dioscin reduced cell death and lactate dehydrogenase (LDH) release in cells subjected to I/R. I/R induced apoptosis and cytochrome c release from mitochondria to the cytosol and this was prevented by dioscin. In support, dioscin decreased Bax but increased Bcl-2 mRNA expression. Dioscin prevented I/R induced dissipation of ΔΨm [3].
Tolvaptan-D7 (OPC-41061-D7) is the deuterium labeled Tolvaptan. Tolvaptan is a selective, competitive arginine vasopressin receptor 2 antagonist with an IC50 of 1.28μM for the inhibition of AVP-induced platelet aggregation[1][2].
Clioquinol(Iodochlorhydroxyquin) is an antifungal drug and antiprotozoal compound that shows effectivity for Alzheimer's disease treatment and induce cancer cell death.
Pseudolaric Acid B is a diterpene isolated from the root of Pseudolarix kaempferi Gorden (pinaceae), has anti-cancer, antifungal, and antifertile activities, and shows immunosuppressive activity on T lymphocytes[1][2][3]. Pseudolaric Acid B inhibits hepatitis B virus (HBV) secretion through apoptosis and cell cycle arrest. Pseudolaric Acid B induces autophagy[4][5].
Carfilzomib is an irreversible proteasome inhibitor with an IC50 of 5 nM in ANBL-6 and RPMI 8226 cells.
Nampt-IN-3 (Compound 35) simultaneously inhibit nicotinamide phosphoribosyltransferase (NAMPT) and HDAC with IC50s of 31 nM and 55 nM, respectively. Nampt-IN-3 effectively induces cell apoptosis and autophagy and ultimately leads to cell death[1].
(±)-Taxifolin ((±)-Dihydroquercetin) is the racemate of Taxifolin. Taxifolin exhibits important anti-tyrosinase activity. Taxifolin exhibits significant inhibitory activity against collagenase with an IC50 value of 193.3 μM[1].
Oxidopamine hydrobromide is a selective catecholaminergic neurotoxin, depletes brain catecholamine levels via uptake and accumulation by a transport mechanism specific to these neurons. In vitro: Oxidopamine hydrobromide-induced apoptosis of PC12 cells was initiated by superoxide generation followed by caspase cascade activation, which was associated with the suppressed Akt phosphorylation and increased p38 phosphorylation. It is likely that pCPT-cAMP prevented the Oxidopamine hydrobromide-induced apoptosis via activation of the PI3-kinase/Akt pathway without any effect on superoxide generation or mitochondrial membrane depolarization. [1]In vivo the presence of sulfhydryl antioxidants protected against neuronal degeneration in the striatum, which was particularly remarkable in the case of CySH and was attributed to its capacity to remove the H2O2 produced in the autoxidation of Oxidopamine hydrobromide.
6-Mercaptopurine-13C2,15N (Mercaptopurine-13C2,15N) is the 13C- and 15N-labeled 6-Mercaptopurine. 6-Mercaptopurine is a purine analogue which acts as an antagonist of the endogenous purines and has been widely used as antileukemic agent and immunosuppressive drug.
Heparin is a highly sulfated glycosaminoglycan,that is widely used as an injectable anticoagulant, and has the highest negative charge density of any known biological molecule.
Gemcitabine (NSC 613327;LY188011) is a DNA synthesis inhibitor which inhibits the growth of BxPC-3, Mia Paca-2, PANC-1, PL-45 and AsPC-1 cells with IC50s of 37.6, 42.9, 92.7, 89.3 and 131.4 nM, respectively.