生物活性

• 靶点	HIF1α IC50:10μM

• 描述Oltipraz is a potent chemopreventive agent which can inhibit the carcinogenicity of many environmental carcinogens in multiple target organs^[6]. It is regarded as an activator of Nrf2. Treatment with Oltipraz led increased nuclear Nrf2 protein in liver sections from Oltipraz -treated mice. Also it led an induction of hepatic Mrp transporters through the Nrf2 transcriptional pathway^[7]. Oltipraz coordinately increases multiple hepatic xenobiotic transporter mRNA levels. Sprague-Dawley rats treated with OPZ exhibited CAR-dependent increased mRNA and protein levels of both Nqo1 and Cyp2b1/2 by 24 h. But it induced microsomal epoxide hydrolase, NAD(P)H quinone oxidoreductase, and Cyp3a1/23, independent of CAR^[8].

• 动物研究
  剂量	Rat: 10 mg/kg[4] (i.v.), 5 mg/kg - 20 mg/kg[5] (i.v.); 30 mg/kg[4] (p.o.), 25 mg/kg - 100 mg/kg[5] (p.o.) Mice: 5 mg/kg - 20 mg/kg[5] (i.v.); 15 mg/kg - 50 mg/kg[5] (p.o.)
  给药途径	i.v., p.o.
  动物药代数据	Animal Rats[4] Dose 10 mg/kg (i.v.) 30 mg/kg (p.o.) Administration i.v. p.o. MRT 61.5 ± 15.6 h (i.v.) F 30.3% (p.o.) T1/2 76.5 ± 18.2 h (i.v.) 129 ± 54.6 h (p.o.) Tmax 390 ± 239 h (p.o.) Cmax 0.286 ± 0.0929 μg/ml (p.o.) Vss 4120 ± 1490 ml/kg (i.v.) AUC 155 ± 26.7 μg·min/ml (i.v.) 141 ± 28.8 μg·min/ml (p.o.)

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT01393678	Chronic Liver Disease	Phase 3	Completed	-	Korea, Republic of ... more >> Hanyang University Hospital Seoul, Seongdong-gu,, Korea, Republic of Collapse <<
  NCT00006457	Lung Cancer	Phase 1	Completed	-	United States, Illinois ... more >> Robert H. Lurie Comprehensive Cancer Center, Northwestern University Chicago, Illinois, United States, 60611-3013 United States, North Carolina Duke Comprehensive Cancer Center Durham, North Carolina, United States, 27710 Collapse <<
  NCT01373554	Non-alcoholic Fatty Liver Dise... more >>ase Collapse <<	Phase 2	Completed	-	Korea, Republic of ... more >> Inje University Ilsan Paik Hospital Dahwa-dong, Ilsanseo-gu, Goyang-si, Gyeonggi-do, Korea, Republic of, 411-706 NHUS Ilsan Hospital Ilsan-ro Ilsan-donggu, Goyang-si, Korea, Republic of, 410-719 Seoul National University Hospital Daehak-ro Jongno-gu, Seoul, Korea, Republic of, 110-744 Korea University Guro hospital Gurodong-ro, Seoul, Korea, Republic of, 152-703 Boramae Hospital Sindaebang-dong Dongjak-gu, Seoul, Korea, Republic of, 156-707 Collapse <<

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• 参考文献

• [1] Manandhar S, Cho JM, et al. Induction of Nrf2-regulated genes by 3H-1, 2-dithiole-3-thione through the ERK signaling pathway in murine keratinocytes. Eur J Pharmacol. 2007 Dec 22;577(1-3):17-27. Epub 2007 Aug 23.

  [2] Maher JM, Dieter MZ, et al. Oxidative and electrophilic stress induces multidrug resistance-associated protein transporters via the nuclear factor-E2-related factor-2 transcriptional pathway. Hepatology. 2007 Nov;46(5):1597-610.

  [3] Merrell MD, Augustine LM, et al. Induction of drug metabolism enzymes and transporters by oltipraz in rats. J Biochem Mol Toxicol. 2008 Mar-Apr;22(2):128-35.

  [4] Lee DY, Kim JW, et al. Pharmacokinetic interaction between oltipraz and omeprazole in rats: Competitive inhibition of metabolism of oltipraz by omeprazole via CYP1A1 and 3A2, and of omeprazole by oltipraz via CYP1A1/2, 2D1/2, and 3A1/2. Eur J Pharm Sci. 2007 Dec;32(4-5):328-39. Epub 2007 Aug 31.

  [5] Bae SK, Lee SJ, et al. Interspecies pharmacokinetic scaling of oltipraz in mice, rats, rabbits and dogs, and prediction of human pharmacokinetics. Biopharm Drug Dispos. 2005 Apr;26(3):99-115.

  [6] Manandhar S, Cho JM, Kim JA, Kensler TW, Kwak MK. Induction of Nrf2-regulated genes by 3H-1, 2-dithiole-3-thione through the ERK signaling pathway in murine keratinocytes. Eur J Pharmacol. 2007 Dec 22;577(1-3):17-27. doi: 10.1016/j.ejphar.2007.08.018. Epub 2007 Aug 23. PMID: 17854798.

  [7] Maher JM, Dieter MZ, Aleksunes LM, Slitt AL, Guo G, Tanaka Y, Scheffer GL, Chan JY, Manautou JE, Chen Y, Dalton TP, Yamamoto M, Klaassen CD. Oxidative and electrophilic stress induces multidrug resistance-associated protein transporters via the nuclear factor-E2-related factor-2 transcriptional pathway. Hepatology. 2007 Nov;46(5):1597-610. doi: 10.1002/hep.21831. PMID: 17668877.

  [8] Merrell MD, Augustine LM, Slitt AL, Cherrington NJ. Induction of drug metabolism enzymes and transporters by oltipraz in rats. J Biochem Mol Toxicol. 2008 Mar-Apr;22(2):128-35. doi: 10.1002/jbt.20225. PMID: 18418891.

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