JNJ-42041935
(Synonyms: HIF-PHD Inhibitor II) 目录号 : GC15379
A selective inhibitor of HIF-PH enzymes
Cas No.:1193383-09-3
Sample solution is provided at 25 µL, 10mM.
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JNJ-42041935 is a potent, competitive and selective inhibitor of prolyl hydroxylase PHD; inhibits PHD1, PHD2, and PHD3 with pKi values of 7.91±0.04, 7.29 ±0.05, and 7.65±0.09, respectively.
JNJ-42041935 is the most potent inhibitor of PHD2181–417 with a pIC50 value of 7.0±0.03. JNJ-42041935 also inhibits full-length PHD1, PHD2, andPHD3 enzymes (pKi values 7.91±0.04, 7.29 ±0.05, and 7.65±0.09, respectively) [1].
JNJ-42041935 is used to compare the effect of selective inhibition of PHD to intermittent, high doses (50 μg/kg i.p.) of an exogenous erythropoietin receptor agonist in an inflammation induced anemia model in rats. JNJ-42041935 (100 μmol/kg, once a day for 14 days) is effective in reversing inflammation induced anemia, whereas erythropoietin has no effect. Administration of JNJ-42041935 (100 μmol/kg p.o.) for 5 consecutive days resulted in a 2-fold increase in reticulocytes, an increase in hemoglobin by 2.3 g/dl, and an increase in the hematocrit of 9%. Two hours after oral administration of 300 μmol/kg JNJ-42041935, the bioluminescence over the peritoneal area is increased by 2.2 ± 0.3-fold relative to luciferase-treated vehicle controls in the mouse [1].
References:
[1]. Barrett TD, et al. Pharmacological characterization of 1-(5-chloro-6-(trifluoromethoxy)-1H-benzoimidazol-2-yl)-1H-pyrazole-4-carboxylic acid (JNJ-42041935), a potent and selective hypoxia-inducible factor prolyl hydroxylase inhibitor. Mol Pharmacol. 2011
Kinase experiment: | The potency of JNJ-42041935 for inhibition of the structurally related enzyme FIH is assessed by methods similar to those described for PHD2. In brief, activity of FIH is determined using purified glutathione transferase-tagged full-length FIH amino acids 1 to 350 and a synthetic HIF-1α peptide corresponding to residues Asp788 to Leu822. Compounds are preincubated with 17.1 nM FIH for 30 min, followed by a 10-min incubation with 1 μM [2-14C]2-oxoglutarate, in the presence of 10 μM FeNH4SO4 in reaction buffer. The selectivity of JNJ-42041935 for inhibition of a range of other targets available for testing in commercial assays is also assessed at concentrations of 1 and 10 μM[1]. |
Animal experiment: | Mice: JNJ-42041935 is administered at doses of 30, 100, and 300 μmol/kg to Balb/C mice . Plasma is collected 6 h after the dose. Plasma erythropoietin concentration is measured. The hematological effects of JNJ-42041935 are assessed by administering the 100 μmol/kg dose on 5 consecutive days and collecting blood anticoagulated with EDTA on day 8 (3 days after the last dose)[1]. |
References: [1]. Barrett TD, et al. Pharmacological characterization of 1-(5-chloro-6-(trifluoromethoxy)-1H-benzoimidazol-2-yl)-1H-pyrazole-4-carboxylic acid (JNJ-42041935), a potent and selective hypoxia-inducible factor prolyl hydroxylase inhibitor. Mol Pharmacol. 2011 | |
| Cas No. | 1193383-09-3 | SDF | |
| 别名 | HIF-PHD Inhibitor II | ||
| 化学名 | 1-[6-chloro-5-(trifluoromethoxy)-1H-benzimidazol-2-yl]-1H-pyrazole-4-carboxylic acid | ||
| Canonical SMILES | ClC1=CC2=C(NC(N3C=C(C(O)=O)C=N3)=N2)C=C1OC(F)(F)F | ||
| 分子式 | C12H6ClF3N4O3 | 分子量 | 346.7 |
| 溶解度 | ≤10mg/ml in ethanol;30mg/ml in DMSO;25mg/ml in dimethyl formamide | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.8843 mL | 14.4217 mL | 28.8434 mL |
| 5 mM | 0.5769 mL | 2.8843 mL | 5.7687 mL |
| 10 mM | 0.2884 mL | 1.4422 mL | 2.8843 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
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2.
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Quality Control & SDS
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- Purity: >99.50%
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