Abstract：
:We examined the tyrosine kinase inhibitor erbstatin and several derivatives for their ability to inhibit serine/threonine protein kinases in vitro. Erbstatin was found to inhibit protein kinase C (PKC) with an IC50 of 19.8 +/- 3.2 microM. A trihydroxy derivative of erbstatin inhibited PKC with similar potency, whereas the corresponding methoxy derivatives were inactive. Inhibition by erbstatin was competitive with ATP (Ki = 11.0 +/- 2.3 microM) and non-competitive with the phosphate acceptor, either histone or the synthetic peptide kemptide. Action of erbstatin at the catalytic site of PKC was further indicated by the findings that it inhibited the catalytic fragment of PKC but did not inhibit the interaction of phorbol ester with the intact enzyme. Erbstatin had a similar potency against three PKC isozymes (alpha, beta, and gamma) examined. In addition, erbstatin was found to inhibit other serine/threonine kinases (assayed at their Km for ATP). The greatest potency was observed versus the cyclic nucleotide-dependent kinases, while lower potency was seen versus myosin light chain kinase. These observations are discussed in terms of the structure and kinetic properties of PKC and the epidermal growth factor receptor tyrosine kinase.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Bishop WR,Petrin J,Wang L,Ramesh U,Doll RJdoi
10.1016/0006-2952(90)90245-gsubject
Has Abstractpub_date
1990-11-01 00:00:00pages
2129-35issue
9eissn
0006-2952issn
1873-2968pii
0006-2952(90)90245-Gjournal_volume
40pub_type
杂志文章abstract：:A selected number of 1,3-diaminobenzo[f]quinazolines and 1,3-diamino-5,6-dihydrobenzo[f]quinazolines, which may be viewed as tricyclic analogues of the lipid-soluble antifolates pyrimethamine (PM), metoprine (DDMP), and etoprine (DDEP), were tested as inhibitors of purified dihydrofolate reductase (DHFR) from WI-L2 ly...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(89)90554-6
更新日期：1989-08-15 00:00:00
abstract：:Irradiation of a cytosolic fraction from vascular smooth muscle in the presence of [3H]felodipine resulted in the labelling of a protein with an apparent molecular weight of 62 kDa. The labelling was seen on UV-irradiation at 360 nm, but not at 254, 278 or at wavelengths above 410 nm. The photolabelling was enhanced i...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(89)90516-9
更新日期：1989-12-01 00:00:00
abstract：:Autophagy is generally regarded as a mechanism to promote cell survival. However, autophagy can occasionally be the mechanism responsible of cell demise. We have found that a concomitant depletion of glucose, nutrients and growth factors provoked cell death in a variety of cell lines. This death process was contingent...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2015.09.021
更新日期：2015-12-15 00:00:00
abstract：:Leydig and Sertoli cells of the rat testes differ with respect to the activities of the enzymes of the heme and hemoprotein degradative pathway and in their responses to Cd2+ treatment. The microsomal heme oxygenase activity in the Leydig cell preparations was nearly 9- to 10-fold greater than in Sertoli cell preparat...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(84)90418-0
更新日期：1984-05-01 00:00:00
abstract：:The role of specific cytochrome P450 (P450) isoforms in the formation of adducts of 7,12-dimethylbenz(a)anthracene metabolites and membrane proteins has been investigated in vitro with microsomal fractions prepared from rats pretreated with various isoenzyme selective inducers. The effects of isoenzyme selective inhib...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(91)90421-z
更新日期：1991-09-27 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90021-n
更新日期：1993-05-25 00:00:00
abstract：:An abnormally high rate of aerobic glycolysis is characteristic of many transformed cells. Here we report the polyphenolic compound, resveratrol, inhibited phosphatidylinositol 3-kinase (PI-3K) signaling and glucose metabolism, coinciding with cell-cycle arrest, in germinal center (GC)-like LY1 and LY18 human diffuse ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2006.08.009
更新日期：2006-11-15 00:00:00
abstract：:Change in the membrane fluidity of human erythrocytes on transformation to stomatocytes was observed by ESR spectroscopy using 12-doxyl stearic acid or its methyl ester as a probe. When the transformation to stomatocytes was induced by four qualitatively different methods, i.e. (a) addition of cationic amphiphilic age...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(82)90546-9
更新日期：1982-10-15 00:00:00
abstract：:Mineralocorticoid receptor (MR) overactivation promotes cardiac fibrosis. We studied the ability of the non-steroidal MR antagonist finerenone to prevent fibrotic remodeling. In neonatal rat cardiac fibroblasts, finerenone prevented aldosterone-induced nuclear MR translocation. Treatment with finerenone decreased the ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2019.07.001
更新日期：2019-10-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(83)90112-0
更新日期：1983-06-01 00:00:00
abstract：:A major problem in the treatment of cancer is cellular resistance to cytotoxic drugs. In tumor cells in vitro, the development of multidrug resistance is usually accompanied by increased expression of drug transporters, either P-glycoprotein (P-gp) or multidrug resistance-associated protein (MRP(1)). Both proteins bel...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(00)00453-6
更新日期：2000-11-15 00:00:00
abstract：:The flavone L86-8275 [(-)cis-5,7-dihydroxy-2-(2-chlorophenyl)-8-[4-(3-hydroxy-1-methyl)- piperidinyl]-4H-1-benzopyran-4-one] delayed the progression of aphidicolin-synchronized MDA-468 breast carcinoma cells through S phase and prevented progression through G2. L86-8275 prevented the G2-related increase in histone H1 ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90590-s
更新日期：1993-11-17 00:00:00
abstract：:Griseofulvin is an anti-fungal drug whose mechanism of action is directed against microtubules. Although it inhibits the assembly of mammalian brain tubulin, its binding to tubulin has not been directly measured successfully. We have examined the interaction of griseofulvin with tubulin fluorometrically by measuring t...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(95)02406-9
更新日期：1996-04-12 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/0006-2952(95)02036-5
更新日期：1996-01-26 00:00:00
abstract：:Enhanced aggregation of platelets was observed in platelet-rich plasma, but not in washed platelet suspension (WPS), during acute inflammation in rats. Incubation of WPS with inflammatory plasma increased the aggregatory response to ADP, but the plasma itself did not cause aggregation of platelets. It potentiated the ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(90)90699-l
更新日期：1990-07-15 00:00:00
abstract：:Rat liver microsomes and purified NADPH-cytochrome c reductase metabolized [14C]misonidazole anaerobically to a reactive intermediate that covalently binds to tissue macromolecules. Air strongly inhibited the binding whereas carbon monoxide had no effect, indicating that misonidazole is activated via reduction and not...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(82)90158-7
更新日期：1982-02-15 00:00:00
abstract：:Zinc protoporphyrin (ZnPP), a known inhibitor of heme oxygenase-1 (HO-1), has been reported to have anticancer activity in both in vitro and in vivo model systems. While the mechanisms of ZnPP's anticancer activity remain to be elucidated, it is generally believed that ZnPP suppresses tumor growth through inhibition o...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2013.03.011
更新日期：2013-06-01 00:00:00
abstract：:In the present study, a screen of adenosine analogs as potential modulators of arylamine-N-acetyltransferase 1 activity identified ATP as an inhibitor within its range of physiological concentrations. Kinetically, ATP was a non-competitive inhibitor with respect to the acetyl acceptor but a competitive inhibitor with ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2018.10.013
更新日期：2018-12-01 00:00:00
abstract：:Matrix metalloproteinases (MMPs), A Disintegrin and Metalloproteinase (ADAM) and A Disintegrin and Metalloproteinase with Thrombospondin Motif (ADAMTS) are zinc-dependent endopeptidases that play a critical role in the destruction of extracellular matrix proteins and, the shedding of membrane-bound receptor molecules ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2019.02.033
更新日期：2019-07-01 00:00:00
abstract：:CYP3A4 is the most important drug-metabolizing enzyme that is involved in biotransformation of more than 50% of drugs. Pregnane X receptor (PXR) dominantly controls CYP3A4 inducibility in the liver, whereas vitamin D receptor (VDR) transactivates CYP3A4 in the intestine by secondary bile acids. Four major functional P...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2009.08.017
更新日期：2010-01-15 00:00:00
abstract：:Hepatic stellate cells (HSCs) are the primary source of matrix components in hepatic fibrosis. Ferulic acid (FA) has antifibrotic potential in renal and cardiac disease. However, whether FA comprises inhibitive effects of HSCs activation remains to be clarified. This study aims at evaluating the hypothesis that FA inh...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2014.10.016
更新日期：2015-01-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(90)90024-f
更新日期：1990-01-15 00:00:00
abstract：:Cancer chemoprevention is a new approach in the management of cancer. Traditional cytotoxic chemotherapeutic approaches cannot cure most advanced solid malignancies. Chemoprevention can be defined as the use of non-cytotoxic drugs and natural agents to block the progression to invasive cancer. Recently, isothiocyanate...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2004.03.044
更新日期：2004-09-15 00:00:00
abstract：:The discipline of biochemical pharmacology emerged in the late 1940s as a result of an increasing emphasis on understanding drug mechanisms at the cellular level. This research approach has contributed significantly to the development of many new drug classes including antihypertensive, antifective, cholesterol loweri...
journal_title：Biochemical pharmacology
pub_type： 历史文章,杂志文章
doi：10.1016/j.bcp.2008.03.024
更新日期：2008-07-01 00:00:00
abstract：:A serine peptidase (RLK1) was partially purified from rat liver homogenates. Its molecular weight was 80,000, and its optimum pH was 7.5. Bz-Tyr-O-Et was hydrolyzed by the enzyme, which was inhibited by Ip2PF, PMSF and by Tos-Phe-CH2Cl. The bonds cleaved by the enzyme were Phe5-Ser6 and Phe8-Arg9, when bradykinin was ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(82)90466-x
更新日期：1982-03-01 00:00:00
abstract：:We recently found that simvastatin can modulate the nuclear factor-kappaB (NF-kappaB) activation pathway, but whether other statins have similar effects to those of simvastatin is unknown. Therefore, we evaluated the effect six different statins on TNF-induced NF-kappaB activation in human myeloid leukemia cells. We t...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2007.10.010
更新日期：2008-02-15 00:00:00
abstract：:A newly synthesized compound, 2-[N-(2-aminoethyl)-N-(5-isoquinolinesulfonyl)]amino-N-(4-chlorocinnamyl )-N-methylbenzylamine (CKA-1306), was found to inhibit cyclic AMP-dependent protein kinase (PKA) and Ca2+/calmodulin-dependent protein kinase I (CaMK I) with IC50 values of 1.6+/-0.14 and 2.5+/-0.16 microM, respectiv...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(98)00157-9
更新日期：1998-08-01 00:00:00
abstract：:The tissue distribution of captopril, an antihypertensive drug possessing a free sulfhydryl group, and its sulfur-conjugated metabolites was studied in rats by gas chromatography-mass spectrometry at 15, 30 and 60 min following a single 10 mg/kg oral dose of captopril. It was found that tissue accumulation of captopri...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(83)90328-3
更新日期：1983-05-15 00:00:00
abstract：:Sulfation of tyrosyl residue(s) has been found to be a post-translational modification that precedes the secretion of many biologically active proteins or peptides. In the present paper, we report on the characterization of human liver tyrosylprotein sulfotransferase (TPST), the enzyme responsible for sulfation of tyr...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(90)90566-4
更新日期：1990-08-01 00:00:00
abstract：:Deoxycytidine kinase (dCK) and deoxycytidine deaminase (dCDA) are two key enzymes in the activation and inactivation, respectively, of deoxycytidine (dCyd) and several chemotherapeutically important nucleoside analogues. To investigate whether supplementation of docosahexaenoic acid, an n-3 fatty acid found mainly in ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(01)00900-5
更新日期：2002-02-15 00:00:00
