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<< Dasatinib >> (BMS-354825) is a novel orally bioavailable SRC/[[ ABL ]] inhibitor that has activity against multiple imatinib-resistant BCR-ABL isoforms in vitro that is presently showing considerable promise in early-phase clinical trials of chronic myeloid leukemia (CML).

Dasatinib (<< BMS-354825 >>) is a novel orally bioavailable [[ SRC ]]/ABL inhibitor that has activity against multiple imatinib-resistant BCR-ABL isoforms in vitro that is presently showing considerable promise in early-phase clinical trials of chronic myeloid leukemia (CML).

Dasatinib (<< BMS-354825 >>) is a novel orally bioavailable SRC/[[ ABL ]] inhibitor that has activity against multiple imatinib-resistant BCR-ABL isoforms in vitro that is presently showing considerable promise in early-phase clinical trials of chronic myeloid leukemia (CML).

In this study, we demonstrate significant inhibitory activity of << dasatinib >> against both wild-type [[ KIT ]] and the KITD816V mutation in the nanomolar range in in vitro and cell-based kinase assays.

In this study, we demonstrate significant inhibitory activity of << dasatinib >> against both wild-type KIT and the [[ KIT ]]D816V mutation in the nanomolar range in in vitro and cell-based kinase assays.

In this study, we demonstrate significant inhibitory activity of << dasatinib >> against both wild-type KIT and the KIT[[ D816V ]] mutation in the nanomolar range in in vitro and cell-based kinase assays.

Additionally, << dasatinib >> leads to growth inhibition of a [[ KIT ]]D816V-harboring human masto-cytosis cell line.

Additionally, << dasatinib >> leads to growth inhibition of a KIT[[ D816V ]]-harboring human masto-cytosis cell line.

Dopamine D(2) receptor-induced << COX-2 >>-mediated production of [[ prostaglandin E(2) ]] in D(2)-transfected Chinese hamster ovary cells without simultaneous administration of a Ca(2+)-mobilizing agent.

The effect was counteracted by the << D(2) >> antagonist [[ eticlopride ]], pertussis toxin, the inhibitor of intracellular Ca(2+) release TMB-8, incubation in Ca(2+)-free experimental medium, and PKC desensitization obtained by chronic pretreatment with the phorbol ester TPA.

It was also antagonized by the non-specific << cyclooxygenase >> (COX) inhibitor, [[ indomethacin ]], and by the selective COX-2 inhibitor, NS-398, but not by the specific COX-1 inhibitor, valeryl salicylate.

It was also antagonized by the non-specific cyclooxygenase (<< COX >>) inhibitor, [[ indomethacin ]], and by the selective COX-2 inhibitor, NS-398, but not by the specific COX-1 inhibitor, valeryl salicylate.

It was also antagonized by the non-specific cyclooxygenase (COX) inhibitor, indomethacin, and by the selective << COX-2 >> inhibitor, [[ NS-398 ]], but not by the specific COX-1 inhibitor, valeryl salicylate.

It was also antagonized by the non-specific cyclooxygenase (COX) inhibitor, indomethacin, and by the selective COX-2 inhibitor, NS-398, but not by the specific << COX-1 >> inhibitor, [[ valeryl salicylate ]].

Both the non-specific << phospholipase A(2) >> inhibitor, [[ quinacrine ]], and an inhibitor of cPLA(2) and iPLA(2), AACOF3, counteracted the effect; in contrast, a selective iPLA(2) inhibitor, BEL, and a selective sPLA(2) inhibitor, TAPC, were ineffective.

The results reinforce previous assumptions that << dopamine >> may interact with eicosanoid metabolism by means of [[ D(2) receptor ]] activation, and implicate an involvement of cPLA(2) and COX-2 in this effect.

A high throughput assay for the glucuronidation of << 7-hydroxy-4-trifluoromethylcoumarin >> by recombinant [[ human UDP-glucuronosyltransferases ]] and liver microsomes.

2.  We have developed a convenient quantitative multi-well plate assay to measure the glucuronidation rate of << 7-hydroxy-4-trifluoromethylcoumarin >> (HFC) for several [[ UGTs ]].

2.  We have developed a convenient quantitative multi-well plate assay to measure the glucuronidation rate of 7-hydroxy-4-trifluoromethylcoumarin (<< HFC >>) for several [[ UGTs ]].

3.  We have used this method to screen 11 recombinant << human UGTs >> for [[ HFC ]] glucuronidation activity and studied the reaction kinetics with the most active enzymes.

4.  At a substrate concentration of 20 µM, the most active << HFC >> glucuronidation catalysts were [[ UGT1A10 ]] followed by UGT1A6 >UGT1A7 >UGT2A1, whereas at 300 µM UGT1A6 was about 10 times better catalyst than the other recombinant UGTs.

4.  At a substrate concentration of 20 µM, the most active << HFC >> glucuronidation catalysts were UGT1A10 followed by [[ UGT1A6 ]] >UGT1A7 >UGT2A1, whereas at 300 µM UGT1A6 was about 10 times better catalyst than the other recombinant UGTs.

4.  At a substrate concentration of 20 µM, the most active << HFC >> glucuronidation catalysts were UGT1A10 followed by UGT1A6 >[[ UGT1A7 ]] >UGT2A1, whereas at 300 µM UGT1A6 was about 10 times better catalyst than the other recombinant UGTs.

4.  At a substrate concentration of 20 µM, the most active << HFC >> glucuronidation catalysts were UGT1A10 followed by UGT1A6 >UGT1A7 >[[ UGT2A1 ]], whereas at 300 µM UGT1A6 was about 10 times better catalyst than the other recombinant UGTs.

4.  At a substrate concentration of 20 µM, the most active << HFC >> glucuronidation catalysts were UGT1A10 followed by UGT1A6 >UGT1A7 >UGT2A1, whereas at 300 µM [[ UGT1A6 ]] was about 10 times better catalyst than the other recombinant UGTs.

4.  At a substrate concentration of 20 µM, the most active << HFC >> glucuronidation catalysts were UGT1A10 followed by UGT1A6 >UGT1A7 >UGT2A1, whereas at 300 µM UGT1A6 was about 10 times better catalyst than the other recombinant [[ UGTs ]].

UGT1A6 exhibited a significantly higher Vmax and Km values toward both << HFC >> and UDP-glucuronic acid than the other [[ UGTs ]].

<< UGT1A6 >> exhibited a significantly higher Vmax and Km values toward both [[ HFC ]] and UDP-glucuronic acid than the other UGTs.

UGT1A6 exhibited a significantly higher Vmax and Km values toward both HFC and << UDP >>-glucuronic acid than the other [[ UGTs ]].

<< UGT1A6 >> exhibited a significantly higher Vmax and Km values toward both HFC and [[ UDP ]]-glucuronic acid than the other UGTs.

UGT1A6 exhibited a significantly higher Vmax and Km values toward both HFC and UDP-<< glucuronic acid >> than the other [[ UGTs ]].

<< UGT1A6 >> exhibited a significantly higher Vmax and Km values toward both HFC and UDP-[[ glucuronic acid ]] than the other UGTs.

This inhibition was blocked when mice were pretreated with the selective << H3R >> agonist [[ R-(alpha)-methyl-histamine ]] (10 mg/kg).

The 5-HT(1/2/5/7)-receptor antagonist methysergide and the 5-HT(2A/2B/2C)-receptor antagonist LY 53857 enhanced clomipramine-induced hyperglycemia, while the << 5-HT(1A/1B)-receptor >> antagonist [[ (-)-propranolol ]] and the 5-HT(3/4)-receptor antagonist tropisetron did not affect it.

The 5-HT(1/2/5/7)-receptor antagonist methysergide and the 5-HT(2A/2B/2C)-receptor antagonist LY 53857 enhanced clomipramine-induced hyperglycemia, while the 5-HT(1A/1B)-receptor antagonist (-)-propranolol and the << 5-HT(3/4)-receptor >> antagonist [[ tropisetron ]] did not affect it.

The 5-HT(1/2/5/7)-receptor antagonist methysergide and the << 5-HT(2A/2B/2C)-receptor >> antagonist [[ LY 53857 ]] enhanced clomipramine-induced hyperglycemia, while the 5-HT(1A/1B)-receptor antagonist (-)-propranolol and the 5-HT(3/4)-receptor antagonist tropisetron did not affect it.

The << 5-HT(2B/2C)-receptor >> antagonist [[ SB 206553 ]] facilitated hyperglycemia induced by clomipramine, although the 5-HT(2A)-receptor antagonist ketanserin was without effect.

The 5-HT(2B/2C)-receptor antagonist SB 206553 facilitated hyperglycemia induced by clomipramine, although the << 5-HT(2A) >>-receptor antagonist [[ ketanserin ]] was without effect.

These results suggest that << clomipramine >> induces hyperglycemia in mice by blocking the [[ 5-HT(2B ) ]]and/or 5-HT(2C) receptors, which results in facilitation of adrenaline release.

These results suggest that << clomipramine >> induces hyperglycemia in mice by blocking the 5-HT(2B )and/or [[ 5-HT(2C) ]] receptors, which results in facilitation of adrenaline release.

<< Phosphatidylserine >> (PtdSer) is made in mammalian cells by two [[ PtdSer synthases ]], PSS1 and PSS2.

<< Phosphatidylserine >> (PtdSer) is made in mammalian cells by two PtdSer synthases, [[ PSS1 ]] and PSS2.

<< Phosphatidylserine >> (PtdSer) is made in mammalian cells by two PtdSer synthases, PSS1 and [[ PSS2 ]].

Moreover, a normal level of expression of << PSS1 >> and/or PSS2 is not required for generating the pool of [[ PtdSer ]] externalized during apoptosis.

Moreover, a normal level of expression of PSS1 and/or << PSS2 >> is not required for generating the pool of [[ PtdSer ]] externalized during apoptosis.

<< PKC >> isoforms did show different sensitivity and selectivity for down-regulation by [[ I3A ]] and phorbol 12-myristate 13-acetate (PMA) in WEHI-231, HOP-92, and Colo-205 cells.

<< PKC >> isoforms did show different sensitivity and selectivity for down-regulation by I3A and [[ phorbol 12-myristate 13-acetate ]] (PMA) in WEHI-231, HOP-92, and Colo-205 cells.

<< PKC >> isoforms did show different sensitivity and selectivity for down-regulation by I3A and phorbol 12-myristate 13-acetate ([[ PMA ]]) in WEHI-231, HOP-92, and Colo-205 cells.

<< I3A >> induced a higher level of secretion of the inflammatory cytokine [[ interleukin 6 ]] compared with PMA in the WEHI-231 cells and displayed a marked biphasic dose-response curve for the induction.

<< I3A >> induced a higher level of secretion of the inflammatory [[ cytokine ]] interleukin 6 compared with PMA in the WEHI-231 cells and displayed a marked biphasic dose-response curve for the induction.

I3A induced a higher level of secretion of the inflammatory cytokine << interleukin 6 >> compared with [[ PMA ]] in the WEHI-231 cells and displayed a marked biphasic dose-response curve for the induction.

I3A induced a higher level of secretion of the inflammatory << cytokine >> interleukin 6 compared with [[ PMA ]] in the WEHI-231 cells and displayed a marked biphasic dose-response curve for the induction.

The in vitro kinase activity of << PKC-alpha >> induced by [[ I3A ]] was lower than that induced by PMA.

The in vitro kinase activity of << PKC-alpha >> induced by I3A was lower than that induced by [[ PMA ]].

<< Type I deiodinase >>, liver fatty-acid binding protein and cytochrome P450 (CYP) 3A37 mRNA levels were significantly induced by [[ TCPP ]], while TDCPP induced CYP3A37 and CYP2H1.

Type I deiodinase, << liver fatty-acid binding protein >> and cytochrome P450 (CYP) 3A37 mRNA levels were significantly induced by [[ TCPP ]], while TDCPP induced CYP3A37 and CYP2H1.

Type I deiodinase, liver fatty-acid binding protein and << cytochrome P450 (CYP) 3A37 >> mRNA levels were significantly induced by [[ TCPP ]], while TDCPP induced CYP3A37 and CYP2H1.

Type I deiodinase, liver fatty-acid binding protein and cytochrome P450 (CYP) 3A37 mRNA levels were significantly induced by TCPP, while << TDCPP >> induced [[ CYP3A37 ]] and CYP2H1.

Type I deiodinase, liver fatty-acid binding protein and cytochrome P450 (CYP) 3A37 mRNA levels were significantly induced by TCPP, while << TDCPP >> induced CYP3A37 and [[ CYP2H1 ]].

The results suggested that both the << EtOAc >> extract and berberine were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine.

The results suggested that both the EtOAc extract and << berberine >> were able to activate [[ PPARα/β/γ ]], and Rhizoma Coptis contains potential natural agonists of PPARs besides berberine.

The results suggested that both the EtOAc extract and berberine were able to activate << PPARα/β/γ >>, and Rhizoma Coptis contains potential natural agonists of PPARs besides [[ berberine ]].

The results suggested that both the EtOAc extract and berberine were able to activate PPARα/β/γ, and Rhizoma Coptis contains potential natural agonists of << PPARs >> besides [[ berberine ]].

This hypothesis was tested by investigating whether, in subjects with essential hypertension, the natriuretic response to specific << renin >>-angiotensin-aldosterone system (RAAS) blockade by renin-inhibitor [[ remikiren ]] could be predicted from pretreatment renal vascular tone.

This hypothesis was tested by investigating whether, in subjects with essential hypertension, the natriuretic response to specific renin-<< angiotensin >>-aldosterone system (RAAS) blockade by renin-inhibitor [[ remikiren ]] could be predicted from pretreatment renal vascular tone.

This hypothesis was tested by investigating whether, in subjects with essential hypertension, the natriuretic response to specific renin-angiotensin-aldosterone system (RAAS) blockade by << renin >>-inhibitor [[ remikiren ]] could be predicted from pretreatment renal vascular tone.

TREK-1 currents are insensitive to pharmacological agents that block << TWIK-1 >> activity such as [[ quinine ]] and quinidine.

TREK-1 currents are insensitive to pharmacological agents that block << TWIK-1 >> activity such as quinine and [[ quinidine ]].

<< CGP 12177A >> mediates cardiostimulation by activation of the 'putative' [[ beta(4)-adrenoceptor ]]; however, it has recently been reported that disruption of the beta(1)-adrenoceptor gene abolishes this effect.

<< CGP 12177A >> mediates cardiostimulation by activation of the 'putative' beta(4)-adrenoceptor; however, it has recently been reported that disruption of the [[ beta(1)-adrenoceptor ]] gene abolishes this effect.

<< CGP 12177A >> but not isoprenaline initiated arrhythmias at lower concentrations following [[ beta(1)-adrenoceptor ]] overexpression.

<< (125)I-Cyanopindolol >> saturation binding in Adv.beta(1) myocytes demonstrated approximately 18-fold increase in [[ beta(1)-adrenoceptors ]].

(3)H-CGP 12177A saturation binding, in the presence of << propranolol >>, increased approximately 5-fold following overexpression of [[ beta(1)-adrenoceptors ]].

<< (3)H-CGP 12177A >> saturation binding, in the presence of propranolol, increased approximately 5-fold following overexpression of [[ beta(1)-adrenoceptors ]].

In contrast, in the presence of << Ca >> UFH accelerated the inhibition of [[ factor Xa ]] by antithrombin 10-fold more efficiently than comparable concentrations of the high affinity fractions of enoxaparin and fragmin.

In contrast, in the presence of << Ca >> UFH accelerated the inhibition of factor Xa by [[ antithrombin ]] 10-fold more efficiently than comparable concentrations of the high affinity fractions of enoxaparin and fragmin.

INTRODUCTION: The principal aim of this study was to assess the efficacy of << quinidine >> in suppressing [[ IKr ]] in vitro and in modulating the rate dependence of the QT interval in the "SQT1" form of the short QT syndrome.

CONCLUSION: Oral << quinidine >> is effective in suppressing the gain of function in [[ IKr ]] responsible for some cases of short QT syndrome with a mutation in HERG and thus restoring normal rate dependence of the QT interval and rendering ventricular tachycardia/ventricular fibrillation noninducible.

The IC50-values obtained for the inhibition of lipopolysaccharide (LPS)-induced release of prostaglandin E2 (PGE2) reflecting << cyclooxygenase (COX)-2 >>-mediated [[ PGE2 ]] release were 47 microg/ml and 0.6 microg/ml, for the Salix extract 1520L and rofecoxib-like research compound L745337, respectively.

Our results indicate that Salix extract 1520L inhibits << COX-2 >>-mediated [[ PGE2 ]] release through compounds other than salicin or salicylate.

<< Follicle-stimulating hormone >> (FSH), a dimeric glycoprotein synthesized in the anterior pituitary gland, is important for the production of sex [[ steroids ]] and gametes.

Follicle-stimulating hormone (<< FSH >>), a dimeric glycoprotein synthesized in the anterior pituitary gland, is important for the production of sex [[ steroids ]] and gametes.

Humans with << FSH beta >> gene mutations tend to have a more severe phenotype than those with FSHR gene mutations, although infertility and varying degrees of impaired sex [[ steroid ]] production occur in both types of mutations.

OBJECTIVES: The aim of the current study was to assess the activity of << rolipram >>, a nonsubtype-selective [[ PDE4 ]] inhibitor, in several animal models predictive of antipsychotic-like efficacy and side-effect liability and to use PDE4B wild-type and knockout mice to begin to understand the subtypes involved in the activity of rolipram.

These results suggest that PDE4B mediates the antipsychotic effects of rolipram in CAR and that the << PDE4B >>-regulated [[ cyclic adenosine monophosphate ]] signaling pathway may play a role in the pathophysiology and pharmacotherapy of psychosis.

<< Cat-1 >>, the transporter for the essential [[ amino acids ]], arginine and lysine, is one of the up-regulated genes.

<< Cat-1 >>, the transporter for the essential amino acids, [[ arginine ]] and lysine, is one of the up-regulated genes.

<< Cat-1 >>, the transporter for the essential amino acids, arginine and [[ lysine ]], is one of the up-regulated genes.

RESULTS: Fractionated bulb extracts and the two isolated << steroidal glycoalkaloids >> (1) and (2) induced NO production and [[ TGF-β receptor I ]] mRNA expression in fibroblast cell culture.

On the basis of data obtained in rabbits, the imidazoline receptor ligand << rilmenidine >> has been suggested to decrease blood pressure in humans by activating central [[ alpha(2A)-adrenoceptors ]].

A prerequisite for this hypothesis was the unproved assumption that rabbit and human << alpha(2A)-adrenoceptors >> are equally activated by [[ rilmenidine ]].

Human atrial appendages and rabbit pulmonary arteries were used to determine the potencies of alpha(2)-adrenoceptor agonists in inhibiting the electrically (2 Hz) evoked [(3)H]norepinephrine release and of antagonists in counteracting the << alpha(2)-adrenoceptor >>-mediated inhibition induced by [[ moxonidine ]].

In the rabbit pulmonary artery, << rilmenidine >> and oxymetazoline are potent full agonists, whereas in the human atrial appendages they are antagonists at the [[ alpha(2)-autoreceptors ]], sharing this property with rauwolscine, phentolamine, and idazoxan.

In the rabbit pulmonary artery, rilmenidine and << oxymetazoline >> are potent full agonists, whereas in the human atrial appendages they are antagonists at the [[ alpha(2)-autoreceptors ]], sharing this property with rauwolscine, phentolamine, and idazoxan.

In the rabbit pulmonary artery, rilmenidine and oxymetazoline are potent full agonists, whereas in the human atrial appendages they are antagonists at the << alpha(2)-autoreceptors >>, sharing this property with [[ rauwolscine ]], phentolamine, and idazoxan.

In the rabbit pulmonary artery, rilmenidine and oxymetazoline are potent full agonists, whereas in the human atrial appendages they are antagonists at the << alpha(2)-autoreceptors >>, sharing this property with rauwolscine, [[ phentolamine ]], and idazoxan.

In the rabbit pulmonary artery, rilmenidine and oxymetazoline are potent full agonists, whereas in the human atrial appendages they are antagonists at the << alpha(2)-autoreceptors >>, sharing this property with rauwolscine, phentolamine, and [[ idazoxan ]].

The sympathetic nerves of both the human atrial appendages and rabbit pulmonary artery are endowed with << alpha(2A)-autoreceptors >>, at which, however, both rilmenidine and [[ oxymetazoline ]] exhibit different properties (antagonism and agonism, respectively).

The sympathetic nerves of both the human atrial appendages and rabbit pulmonary artery are endowed with << alpha(2A)-autoreceptors >>, at which, however, both [[ rilmenidine ]] and oxymetazoline exhibit different properties (antagonism and agonism, respectively).

The antagonistic property of << rilmenidine >> at [[ human alpha(2A)-adrenoceptors ]] indicates that in contrast to the suggestion based on rabbit data, the hypotensive property of the drug in humans is not due to activation of alpha(2A)-adrenoceptors but other, presumably I(1)-imidazoline receptors, are probably involved.