Virtual screening-based discovery and mechanistic characterization of the acylthiourea MRT-10 family as smoothened antagonists.

abstract：:Histone deacetylase inhibitors (HDACi), which have emerged as a new class of anticancer agents, act by modulating expression of genes controlling apoptosis or cell proliferation. Here, we compared the effect of HDACi on transcriptional activation by estrogen or glucocorticoid receptors (ER and GR, respectively), two m...

journal_title：Molecular pharmacology

authors： Rocha W,Sanchez R,Deschênes J,Auger A,Hébert E,White JH,Mader S

更新日期：2005-12-01 00:00:00

abstract：:Phosphodiesterase-9 (PDE9) inhibitors have been studied as potential therapeutics for treatment of central nervous system diseases and diabetes. Here, we report the discovery of a new category of PDE9 inhibitors by rational design on the basis of the crystal structures. The best compound, (S)-6-((1-(4-chlorophenyl)eth...

journal_title：Molecular pharmacology

authors： Huang M,Shao Y,Hou J,Cui W,Liang B,Huang Y,Li Z,Wu Y,Zhu X,Liu P,Wan Y,Ke H,Luo HB

更新日期：2015-11-01 00:00:00

abstract：:Isoproterenol increases and decreases contractile force at low and high concentrations, respectively, through beta(2)-adrenoceptors overexpressed in transgenic mouse heart (TG4), consistent with activation of both G(s) and G(i) proteins. Using TG4 hearts, we demonstrated that epinephrine behaves like isoproterenol, bu...

journal_title：Molecular pharmacology

authors： Heubach JF,Ravens U,Kaumann AJ

更新日期：2004-05-01 00:00:00

abstract：:To study the functional role of individual alpha1-adrenergic (AR) subtypes in blood pressure (BP) regulation, we used mice lacking the alpha1B-AR and/or alpha1D-AR with the same genetic background and further studied their hemodynamic and vasoconstrictive responses. Both the alpha1D-AR knockout and alpha1B-/alpha1D-AR...

journal_title：Molecular pharmacology

authors： Hosoda C,Koshimizu TA,Tanoue A,Nasa Y,Oikawa R,Tomabechi T,Fukuda S,Shinoura H,Oshikawa S,Takeo S,Kitamura T,Cotecchia S,Tsujimoto G

更新日期：2005-03-01 00:00:00

abstract：:Recently, several classes of compounds have been shown to be potent, selective, and specific inhibitors of human immunodeficiency virus type 1 replication in vitro. These include the tetrahydroimidazo[4,5,1-jk][1,4]-benzodiazepin-2(1H)-one and -thione (TIBO) and the 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (H...

journal_title：Molecular pharmacology

authors： Debyser Z,Pauwels R,Baba M,Desmyter J,De Clercq E

更新日期：1992-05-01 00:00:00

abstract：:Schizophrenia (SZ), schizoaffective (SZA), and bipolar (BP) disorder are neurodevelopmental psychopathological conditions related, in part, to genetic load and, in part, to environmentally induced epigenetic dysregulation of chromatin structure and function in neocortical GABAergic, glutamatergic, and monoaminergic ne...

journal_title：Molecular pharmacology

authors： Dong E,Locci V,Gatta E,Grayson DR,Guidotti A

更新日期：2019-01-01 00:00:00

abstract：:Tritiated dextromethorphan ([3H]DM) binds to two distinct sites in guinea pig brain, a high-affinity site (Kd = 13-20 nM) and a low-affinity site (Kd greater than 200 nM). Binding of [3H] DM to the high-affinity site is rapid, reversible, saturable, proportional to tissue concentration, and pH-dependent. The sites hav...

journal_title：Molecular pharmacology

authors： Craviso GL,Musacchio JM

更新日期：1983-05-01 00:00:00

abstract：:Ethanol (ETOH) can cause apoptotic death of neurons by depleting GSH with an associated increase in oxidative stress. The current study illustrates a means to overcome this ETOH-induced neurotoxicity by enhancing GSH through boosting Nrf2, a transcription factor that controls GSH homeostasis. ETOH treatment caused a s...

journal_title：Molecular pharmacology

authors： Narasimhan M,Mahimainathan L,Rathinam ML,Riar AK,Henderson GI

更新日期：2011-12-01 00:00:00

abstract：:High-affinity glycine transport in neurons and glial cells is a primary means of inactivating synaptic glycine. We have synthesized a potent selective inhibitor of glycine transporter 1 (GlyT1), and characterized its activity using a quail fibroblast cell line (QT6). The glycine transporters GlyT1A, GlyT1B, GlyT1C, an...

journal_title：Molecular pharmacology

authors： Atkinson BN,Bell SC,De Vivo M,Kowalski LR,Lechner SM,Ognyanov VI,Tham CS,Tsai C,Jia J,Ashton D,Klitenick MA

更新日期：2001-12-01 00:00:00

abstract：:The synthetic alpha-conotoxin Vc1.1 is a small disulfide bonded peptide currently in development as a treatment for neuropathic pain. Unlike Vc1.1, the native post-translationally modified peptide vc1a does not act as an analgesic in vivo in rat models of neuropathic pain. It has recently been proposed that the primar...

journal_title：Molecular pharmacology

authors： Nevin ST,Clark RJ,Klimis H,Christie MJ,Craik DJ,Adams DJ

更新日期：2007-12-01 00:00:00

abstract：:As noted previously, in N1E-115 neuroblastoma cells, carbamylcholine, a muscarinic cholinergic agonist, increased cGMP over 15-fold and decreased basal and prostaglandin E1 (PGE1)-stimulated cAMP content. In contrast to the stimulatory effects of PGE1 on cAMP, which were immediate, the carbamylcholine-induced decrease...

journal_title：Molecular pharmacology

authors： Bruni P,Burns DL,Hewlett EL,Moss J

更新日期：1985-08-01 00:00:00

abstract：:Endothelin (ET) receptors are present in pituitary cells and stimulate hormone release through the phosphoinositide/Ca2+ signaling system. In pituitary cell suspensions, ET caused [Ca2+]i elevations of much higher amplitudes than those induced by other vasoactive hormones, including angiotensin II, vasopressin, and no...

journal_title：Molecular pharmacology

authors： Stojilković SS,Iida T,Merelli F,Catt KJ

更新日期：1991-06-01 00:00:00

abstract：:Adenosine receptors of the A1 and A2 subtypes were characterized in membranes from DDT1 MF-2 smooth muscle cells. These cells possess a high density of A1 adenosine receptors (Bmax = 0.8-0.9 pmol/mg of protein), as measured by both agonist and antagonist radioligands. Agonists compete for [125I]N6-[2-(4-amino-3-iodoph...

journal_title：Molecular pharmacology

authors： Ramkumar V,Barrington WW,Jacobson KA,Stiles GL

更新日期：1990-02-01 00:00:00

abstract：:Previously, we showed that the human kappa-opioid receptor (hkor) stably expressed in Chinese hamster ovary (CHO) cells underwent down-regulation after prolonged U50,488H treatment. In the present study, we determined the mechanisms underlying this process. U50, 488H caused a significant down-regulation of the hkor, a...

journal_title：Molecular pharmacology

authors： Li JG,Benovic JL,Liu-Chen LY

更新日期：2000-10-01 00:00:00

abstract：:The molecular determinants of high-affinity human ether-a-go-go-related gene (HERG) potassium channel blockade by methanesulfonanilides include two aromatic residues (Phe656 and Tyr652) on the inner helices (S6) and residues on the pore helices that face into the inner cavity, but determinants for lower-affinity HERG ...

journal_title：Molecular pharmacology

authors： Witchel HJ,Dempsey CE,Sessions RB,Perry M,Milnes JT,Hancox JC,Mitcheson JS

更新日期：2004-11-01 00:00:00

abstract：:The sulfoconjugation of tyrosyl residues is a widespread post-translational modification of biologically active proteins and peptides. The rat liver Golgi enzyme tyrosylprotein sulfotransferase has previously been shown to catalyze the transfer of a sulfate moiety from 5'-phosphoadenosine-3'-phosphosulfate to the synt...

journal_title：Molecular pharmacology

authors： Rens-Domiano S,Hortin GL,Roth JA

更新日期：1989-10-01 00:00:00

abstract：:An alteration in the balance between a T-helper type 2 cell (Th2) response and a Th1 response may predispose to the development of bronchial asthma. Interleukin-18 (IL-18) has an ability to promote both Th1 and Th2 responses, depending on the surrounding cytokine environment. Reactive oxygen species (ROS) play a cruci...

journal_title：Molecular pharmacology

authors： Lee KS,Kim SR,Park SJ,Min KH,Lee KY,Jin SM,Yoo WH,Lee YC

更新日期：2006-10-01 00:00:00

abstract：:To identify novel factors or mechanisms that are important for the resistance of tissues to chemical toxicity, we have determined the mechanisms underlying the previously observed increases in resistance to acetaminophen (APAP) toxicity in the lateral nasal gland (LNG) of the male Cyp2g1-null/Cyp2a5-low mouse. Initial...

journal_title：Molecular pharmacology

authors： Zhou X,Wei Y,Xie F,Laukaitis CM,Karn RC,Kluetzman K,Gu J,Zhang QY,Roberts DW,Ding X

更新日期：2011-04-01 00:00:00

abstract：:Westernization of dietary habits increases lipid intake and is responsible for increased numbers of patients with atherosclerotic diseases. Niemann-Pick C1-Like 1 (NPC1L1)-a cholesterol importer-plays a crucial role in dietary cholesterol absorption in the intestine and is closely associated with several lipid-related...

journal_title：Molecular pharmacology

authors： Yamamoto H,Yamanashi Y,Takada T,Mu S,Tanaka Y,Komine T,Suzuki H

更新日期：2019-07-01 00:00:00

abstract：:Previous studies have established that two Xbal polymorphic restriction fragments [11.5 and 44 kilobases (kb)] hydridizing to a full length debrisoquin hydroxylase cDNA are associated with two different mutant alleles for the debrisoquin hydroxylase gene (IID6). An independent allele, defined by Xbal 16- and 9-kb frag...

journal_title：Molecular pharmacology

authors： Evans WE,Relling MV

更新日期：1990-05-01 00:00:00

abstract：:The effects of saturating concentrations of DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane] and the pyrethroid insecticides cismethrin and deltamethrin on alkaloid-dependent activation of the voltage-sensitive sodium channel were studied using measurements of 22Na+ uptake into mouse brain synaptosomes. In survey e...

journal_title：Molecular pharmacology

authors： Bloomquist JR,Soderlund DM

更新日期：1988-05-01 00:00:00

abstract：:Human and bovine dopamine transporters (DAT) demonstrate discrete functional differences in dopamine (DA), 1-methyl-4-phenylpyridium (MPP(+)) transport, and cocaine analog binding. In a previous study, the functional analyses on the chimeras of human and bovine DAT have revealed that the region from residues 133 throu...

journal_title：Molecular pharmacology

authors： Lee SH,Chang MY,Lee KH,Park BS,Lee YS,Chin HR,Lee YS

更新日期：2000-05-01 00:00:00

abstract：:Rat cerebellar granule cells express 5-hydroxytryptamine (5-HT)2 receptors that mediate phosphoinositide turnover by a pertussis toxin-sensitive mechanism. Prestimulation of these neurons with 10 microM 5-HT or (+/-)-2,5-dimethoxy-4-iodophenyl-2-aminopropane [(+/-)-DOI], a putative 5-HT2 receptor agonist, resulted in ...

journal_title：Molecular pharmacology

authors： Akiyoshi J,Hough C,Chuang DM

更新日期：1993-03-01 00:00:00

abstract：:Understanding the molecular basis of ligand binding to receptors provides insights useful for rational drug design. This work describes development of a new antagonist radioligand of the type 1 cholecystokinin receptor (CCK1R), (2-fluorophenyl)-2,3-dihydro-3-[(3-isoquinolinylcarbonyl)amino]-6-methoxy-2-oxo-l-H-indole-...

journal_title：Molecular pharmacology

authors： Dong M,Vattelana AM,Lam PC,Orry AJ,Abagyan R,Christopoulos A,Sexton PM,Haines DR,Miller LJ

更新日期：2015-01-01 00:00:00

abstract：:The relationship between the phospholipase-stimulating and immunosuppressive properties of cyclosporin A (CsA) has been investigated in vitro. At concentrations of 0.025 microM and upwards, CsA caused dose-related inhibition of both mitogen- and alloantigen-stimulated uptake of tritiated thymidine by human mononuclear...

journal_title：Molecular pharmacology

authors： Anderson R,Smit MJ,Van Rensburg CE

更新日期：1993-09-01 00:00:00

abstract：:In the last years, reactive oxygen species (ROS) have been proposed as mediators of proliferative/hypertrophic responses to angiotensin II (Ang II), both in vivo and in vitro. However, the hypothesis that the Ang II-dependent cell contraction could be mediated by ROS, particularly H2O2, has not been tested. Present ex...

journal_title：Molecular pharmacology

authors： Torrecillas G,Boyano-Adánez MC,Medina J,Parra T,Griera M,López-Ongil S,Arilla E,Rodríguez-Puyol M,Rodríguez-Puyol D

更新日期：2001-01-01 00:00:00

abstract：:Poly(A)+ RNA from mammalian retina expresses bicuculline/baclofen-insensitive gamma-aminobutyric acid (GABA) receptors in Xenopus oocytes with properties similar to those of homooligomeric GABA rho 1 receptors. The pharmacological profile of these rho-like receptors was extended by measuring sensitivities to various G...

journal_title：Molecular pharmacology

authors： Woodward RM,Polenzani L,Miledi R

更新日期：1993-04-01 00:00:00

abstract：:The L-type amino acid transporter 1 (LAT1) is an Na(+)-independent neutral amino acid transporter subserving the amino acid transport system L. Because of its broad substrate selectivity, system L has been proposed to be responsible for the permeation of amino acid-related drugs through the plasma membrane. To underst...

journal_title：Molecular pharmacology

authors： Uchino H,Kanai Y,Kim DK,Wempe MF,Chairoungdua A,Morimoto E,Anders MW,Endou H

更新日期：2002-04-01 00:00:00

abstract：:The mechanisms underlying mastoparan-induced elevation of the intracellular free calcium concentration ([Ca2+]i) were investigated in the insulin-secreting cell lines RINm5F and HIT. In both cell types, micromolar concentrations of mastoparan induced a prompt increase of [Ca2+]i, measured as an increase in fura-2 fluo...

journal_title：Molecular pharmacology

authors： Eddlestone GT,Komatsu M,Shen L,Sharp GW

更新日期：1995-04-01 00:00:00

abstract：:The action of tetrahydroaminoacridine (THA), a centrally active cholinesterase inhibitor that may provide symptomatic benefit in Alzheimer's disease, was studied on responses to the excitatory amino acid N-methyl-D-aspartate (NMDA) in cultured hippocampal neurons, using whole-cell voltage-clamp and single-channel reco...

journal_title：Molecular pharmacology

authors： Hershkowitz N,Rogawski MA

更新日期：1991-05-01 00:00:00