Abstract：
:Histone deacetylase inhibitors (HDACis) are currently in trial or are in clinical use for the treatment of a number of tumor types. The clinical efficacy of HDACis can be partly attributed to the modulation of the cell cycle by the HDACis. Here, we have examined the effects of N-(2-aminophenyl)-4-((4-pyridin-3-ylpyrimidin-2-ylamino)methyl)benzamide (MGCD0103), a class I-selective histone deacetylase inhibitor, on the cell cycle and cell killing. Surprisingly, MGCD0103 treatment failed to initiate a G(1)-phase arrest but caused marked accumulation of cells in G(2)/M at 6 and 12 h after treatment and was cytotoxic 24 h after treatment. These cell cycle effects were considerably distinct from the effects of suberic bishydroxamic acid, a representative of the pan-isoform HDACi used in this study. MGCD0103 shared the ability of the pan-isoform HDACi to trigger defective mitosis and promote mitotic slippage. Likewise, it also specifically targeted tumor cells and was nontoxic to normal nontransformed cells. However, MGDC0103 also seemed to disrupt normal microtubule spindle formation, whereas HDACis generally have only a minor effect on spindle formation. The effect of MGCD0103 on spindle formation was shown to be a consequence of microtubule destabilization. This is the first example of an HDACi with microtubule destabilizing activity, and the combined effects of this drug have advantages for its therapeutic use.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Chia K,Beamish H,Jafferi K,Gabrielli Bdoi
10.1124/mol.110.065169subject
Has Abstractpub_date
2010-09-01 00:00:00pages
436-43issue
3eissn
0026-895Xissn
1521-0111pii
mol.110.065169journal_volume
78pub_type
杂志文章abstract：:The ability of dopamine agonists and antagonists to compete with [3H]spiperone binding to rat striatal membrane preparations at 4, 15, 26, and 37 degrees varied markedly with temperature. Dopamine and the dopamine agonist 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene hydrobromide (ADTN) were more potent at lower...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1986-09-01 00:00:00
abstract：:The relationship between receptor number and agonist-induced intracellular responses has been well studied in receptors coupled to adenylate cyclase; however, for receptors coupled to phospholipase C (PLC), very little is known about the effect of receptor number on receptor-mediated processes. To explore this issue, ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.51.5.721
更新日期：1997-05-01 00:00:00
abstract：:Tetrodotoxin-sensitive Na(+) currents have been extensively studied because they play a major role in neuronal firing and bursting. In this study, we showed that voltage-dependent Na(+) currents are regulated in a slow manner by oxotremorine (oxo-M) and angiotensin II in rat sympathetic neurons. We found that these cu...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.115.101931
更新日期：2016-04-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.52.6.1010
更新日期：1997-12-01 00:00:00
abstract：:Typical equilibrium binding experiments cannot be quantitatively analyzed on the basis of classical mathematical equations when the receptor concentration is so high that a significant fraction of the added radioligand concentration is in the bound form. In this paper, the appropriate equations are derived and used in...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1995-06-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1983-05-01 00:00:00
abstract：:Nitric oxide (NO) possesses potent anti-inflammatory properties; however, an over-production of NO will promote inflammation and induce cell and tissue dysfunction. Thus, the ability to precisely regulate NO production could prove beneficial in controlling damage. In this study, advantage was taken of the well charact...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.59.4.939
更新日期：2001-04-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.115.101808
更新日期：2016-04-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/molpharm.120.000079
更新日期：2021-01-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.53.1.128
更新日期：1998-01-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-09-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1988-09-01 00:00:00
abstract：:In rat pancreatic zymogen granules (ZG), an ATP-sensitive K(+) conductance and a Cl(-) conductance have been characterized that are inversely regulated by an approximately 65-kDa multidrug resistance P-glycoprotein (mdr1) gene product. In search of a label for purification of this protein, we found that the dihydropyr...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：2000-02-01 00:00:00
abstract：:Mitsuya and Broder [Proc. Natl. Acad. Sci. USA 83:1911-1915 (1986)] demonstrated that every purine (adenosine, guanosine, and inosine) and pyrimidine (cytidine and thymidine) nucleoside containing the 2',3'-dideoxyribose configuration, when evaluated against human immunodeficiency virus (HIV) in vitro, significantly s...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1988-10-01 00:00:00
abstract：:We describe the nucleic acid sequence encoding a human 5-hydroxytryptamine1D (5-HT1D) serotonin receptor and some of the functional characteristics of the gene product. The receptor gene was isolated by hybridization to a probe based on a canine thyroid cDNA (called RDC4) previously isolated by others and believed to ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-08-01 00:00:00
abstract：:Thymidine phosphorylase (TPase) is one of the key enzymes involved in the pyrimidine nucleoside salvage pathway. However, TPase also stimulates angiogenesis, and its expression correlates well with microvessel density and metastasis in a variety of human tumors. We have shown recently that 5'-O-trityl-inosine (KIN59) ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.105.021188
更新日期：2006-08-01 00:00:00
abstract：:Seven transmembrane G protein-coupled receptors (GPCRs) are often phosphorylated at the C terminus and on intracellular loops in response to various extracellular stimuli. Phosphorylation of GPCRs by GPCR kinases and certain other kinases can promote the recruitment of arrestin molecules. The arrestins critically regu...
journal_title：Molecular pharmacology
pub_type： 杂志文章,评审
doi：10.1124/mol.116.107839
更新日期：2017-09-01 00:00:00
abstract：:The c-Myc (MYC) transcription factor is a major cancer driver and a well-validated therapeutic target. However, directly targeting MYC has been challenging. Thus, identifying proteins that interact with and regulate MYC may provide alternative strategies to inhibit its oncogenic activity. In this study, we report the ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.116.107623
更新日期：2017-04-01 00:00:00
abstract：:The aryl hydrocarbon receptor (AHR) binds planar aromatic compounds and up-regulates the transcription of a battery of xenobiotic-metabolizing enzymes. To identify proteins involved in the biosynthesis of endogenous AHR ligands, we screened extracts of various mouse tissues for AHR signaling activity. We found heart e...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.64.3.550
更新日期：2003-09-01 00:00:00
abstract：:Bioassay-guided fractionation was used to isolate the lignan polygamain as the microtubule-active constituent in the crude extract of the Mountain torchwood, Amyris madrensis. Similar to the effects of the crude plant extract, polygamain caused dose-dependent loss of cellular microtubules and the formation of aberrant...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.111.075838
更新日期：2012-03-01 00:00:00
abstract：:A collection of analogues of atrial natriuretic peptide (ANP) were screened for their ability to inhibit ANP-induced cGMP stimulation. The antagonists revealed through this screen are structurally related; almost all are substituted at either aspartate-13 or phenylalanine-26. This tendency is consistent throughout sev...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1990-12-01 00:00:00
abstract：:Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are members of the phospholipid growth factor family. A major limitation in the field to date has been a lack of receptor subtype-specific agonists and antagonists. Here, we report that dioctylglycerol pyrophosphate and dioctylphosphatidic acid are selectiv...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：2001-10-01 00:00:00
abstract：:Chimeric receptors of the beta2-adrenergic receptor in which the extracellular loops were replaced with the corresponding amino acids of the alpha1a-adrenergic receptor were generated to measure changes in alpha1-antagonist affinity. Although no changes in alpha1-antagonist affinity were measured in the beta2/alpha1a ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.53.3.524
更新日期：1998-03-01 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
pub_type： 杂志文章
doi：10.1124/mol.118.113415
更新日期：2019-01-01 00:00:00
abstract：:Several structurally related series of folate analogs were studied as substrates for mouse liver folylpolyglutamate synthetase (FPGS). A comparison of the kinetics of the interaction of this enzyme with folate analogs that contained the quinazoline ring in place of the pteridine ring with those of the analogous pterid...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1989-11-01 00:00:00
abstract：:The human dopamine and norepinephrine transporters (hDAT and hNET, respectively) control neurotransmitter levels within the synaptic cleft and are the site of action for amphetamine (AMPH) and cocaine. We investigated the role of a threonine residue within the highly conserved and putative phosphorylation sequence RET...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.110.069039
更新日期：2011-03-01 00:00:00
abstract：:Bryostatin 1 and phorbol-12-myristate-13-acetate (PMA) are both potent activators of protein kinase C (PKC), although in primary mouse keratinocytes bryostatin 1 does not induce differentiation and blocks PMA-induced differentiation. We report here that in primary mouse keratinocytes PMA caused translocation of PKC-ep...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1994-11-01 00:00:00
abstract：:Fusion proteins between the human 5-hydroxytryptamine (5-HT)(1A) receptor and either wild type or certain pertussis toxin-resistant forms of G(o1)alpha and G(i1)alpha display constitutive GTPase activity that can be inhibited by the inverse agonist spiperone. Addition of recombinant regulator of G protein signaling (R...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.61.5.1211
更新日期：2002-05-01 00:00:00
abstract：:The effect of mercuric acetate on the activities of deoxyuridine triphosphate nucleotidohydrolase (dUTPase), DNA polymerase (alpha, beta), and uracil-DNA glycosylase has been studied in cultured human KB cells. There was a dose- and time-dependent inactivation of both dUTPase and DNA polymerase alpha activities by mer...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1987-02-01 00:00:00
abstract：:Acute desensitization of mu opioid receptors is thought to be an initial step in the development of tolerance to opioids. Given the resistance of the respiratory system to develop tolerance, desensitization of neurons in the Kölliker-Fuse (KF), a key area in the respiratory circuit, was examined. The activation of G p...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.117.109603
更新日期：2018-01-01 00:00:00
