Pactimibe (BioDeep_00000182044)
human metabolite blood metabolite
代谢物信息卡片
化学式: C25H40N2O3 (416.3039)
中文名称: 帕替麦布
谱图信息:
最多检出来源 () 0%
分子结构信息
SMILES: CCCCCCCCN1CCC2=C(C(=C(C(=C21)NC(=O)C(C)(C)C)C)CC(=O)O)C
InChI: InChI=1S/C25H40N2O3/c1-7-8-9-10-11-12-14-27-15-13-19-17(2)20(16-21(28)29)18(3)22(23(19)27)26-24(30)25(4,5)6/h7-16H2,1-6H3,(H,26,30)(H,28,29)
描述信息
D006133 - Growth Substances > D010937 - Plant Growth Regulators > D007210 - Indoleacetic Acids
C471 - Enzyme Inhibitor
Pactimibe (CS-505 free base) is a dual ACAT1/2 inhibitor with IC50s of 4.9 μM and 3.0 μM, respectively. Pactimibe (CS-505 free base) inhibits ACAT with IC50s of 2.0 μM, 2.7 μM, 4.7 μM in the liver, macrophages and THP-1 cells, respectively[1]. Pactimibe (CS-505 free base) noncompetitively inhibits oleoyl-CoA with a Ki value of 5.6 μM. Moreover, Pactimibe (CS-505 free base) obviously inhibits cholesteryl ester formation with an IC50 of 6.7 μM. Pactimibe (CS-505 free base) possesses anti-atherosclerotic potential with lowering plasma cholesterol activity[2].
同义名列表
6 个代谢物同义名
2-{7-[(1-hydroxy-2,2-dimethylpropylidene)amino]-4,6-dimethyl-1-octyl-2,3-dihydro-1H-indol-5-yl}acetate; 2-[7-(2,2-dimethylpropanamido)-4,6-dimethyl-1-octyl-2,3-dihydro-1H-indol-5-yl]acetic acid; (7-(2,2-dimethylpropanamido)-4,6-Dimethyl-1-octylindolin-5-yl)acetic acid hemisulfate; Pactimibe sulfate; Pactimibe; CS-505 (free base)
数据库引用编号
7 个数据库交叉引用编号
- PubChem: 3081927
- HMDB: HMDB0256074
- DrugBank: DB12971
- ChEMBL: CHEMBL478858
- chemspider: 2339427
- CAS: 189198-30-9
- medchemexpress: HY-100401
分类词条
相关代谢途径
Reactome(0)
BioCyc(0)
PlantCyc(0)
代谢反应
0 个相关的代谢反应过程信息。
Reactome(0)
BioCyc(0)
WikiPathways(0)
Plant Reactome(0)
INOH(0)
PlantCyc(0)
COVID-19 Disease Map(0)
PathBank(0)
PharmGKB(0)
1 个相关的物种来源信息
在这里通过桑基图来展示出与当前的这个代谢物在我们的BioDeep知识库中具有相关联信息的其他代谢物。在这里进行关联的信息来源主要有：
- PubMed: 来源于PubMed文献库中的文献信息，我们通过自然语言数据挖掘得到的在同一篇文献中被同时提及的相关代谢物列表，这个列表按照代谢物同时出现的文献数量降序排序，取前10个代谢物作为相关研究中关联性很高的代谢物集合展示在桑基图中。
- NCBI Taxonomy: 通过文献数据挖掘，得到的代谢物物种来源信息关联。这个关联信息同样按照出现的次数降序排序，取前10个代谢物作为高关联度的代谢物集合展示在桑吉图上。
- Chemical Taxonomy: 在物质分类上处于同一个分类集合中的其他代谢物
- Chemical Reaction: 在化学反应过程中，存在为当前代谢物相关联的生化反应过程中的反应底物或者反应产物的关联代谢物信息。
点击图上的相关代谢物的名称，可以跳转到相关代谢物的信息页面。
文献列表
- Keisuke Eguchi, Yukio Fujiwara, Akinori Hayashida, Hasita Horlad, Hikaru Kato, Henki Rotinsulu, Fitje Losung, Remy E P Mangindaan, Nicole J de Voogd, Motohiro Takeya, Sachiko Tsukamoto. Manzamine A, a marine-derived alkaloid, inhibits accumulation of cholesterol ester in macrophages and suppresses hyperlipidemia and atherosclerosis in vivo.
Bioorganic & medicinal chemistry.
2013 Jul; 21(13):3831-8. doi:
10.1016/j.bmc.2013.04.025. [PMID: 23665143] - Sung-Hee Cho, Eun-Jung Park, Eun-Ok Kim, Sang-Won Choi. Study on the hypochlolesterolemic and antioxidative effects of tyramine derivatives from the root bark of Lycium chenese Miller.
Nutrition research and practice.
2011 Oct; 5(5):412-20. doi:
10.4162/nrp.2011.5.5.412. [PMID: 22125678] - Yasunobu Yoshinaka, Haruki Shibata, Hideyuki Kobayashi, Hiroki Kuriyama, Kimiyuki Shibuya, Sohei Tanabe, Takuya Watanabe, Akira Miyazaki. A selective ACAT-1 inhibitor, K-604, stimulates collagen production in cultured smooth muscle cells and alters plaque phenotype in apolipoprotein E-knockout mice.
Atherosclerosis.
2010 Nov; 213(1):85-91. doi:
10.1016/j.atherosclerosis.2010.08.048. [PMID: 20843517] - Kenji Takahashi, Masaru Ohta, Yoshimichi Shoji, Masayasu Kasai, Kazuyoshi Kunishiro, Tomohiro Miike, Mamoru Kanda, Hiroaki Shirahase. Novel acyl-CoA: cholesterol acyltransferase inhibitor: indoline-based sulfamide derivatives with low lipophilicity and protein binding ratio.
Chemical & pharmaceutical bulletin.
2010 Aug; 58(8):1057-65. doi:
10.1248/cpb.58.1057. [PMID: 20686260] - Masaru Ohta, Kenji Takahashi, Masayasu Kasai, Yoshimichi Shoji, Kazuyoshi Kunishiro, Tomohiro Miike, Mamoru Kanda, Chisato Mukai, Hiroaki Shirahase. Novel tetrahydroisoquinoline derivatives with inhibitory activities against acyl-CoA: cholesterol acyltransferase and lipid peroxidation.
Chemical & pharmaceutical bulletin.
2010 Aug; 58(8):1066-76. doi:
10.1248/cpb.58.1066. [PMID: 20686261] - Yoshimichi Shoji, Kenji Takahashi, Masaru Ohta, Masayasu Kasai, Kazuyoshi Kunishiro, Mamoru Kanda, Satoko Yogai, Yasuo Takeuchi, Hiroaki Shirahase. Novel indoline-based acyl-CoA: cholesterol acyltransferase inhibitor: Effects of introducing a methanesulfonamide group on physicochemical properties and biological activities.
Bioorganic & medicinal chemistry.
2009 Aug; 17(16):6020-31. doi:
10.1016/j.bmc.2009.06.047. [PMID: 19608421] - Marijn C Meuwese, Eric de Groot, Raphaël Duivenvoorden, Mieke D Trip, Leiv Ose, Frans J Maritz, Dick C G Basart, John J P Kastelein, Rafik Habib, Michael H Davidson, Aeilko H Zwinderman, Lee R Schwocho, Evan A Stein. ACAT inhibition and progression of carotid atherosclerosis in patients with familial hypercholesterolemia: the CAPTIVATE randomized trial.
JAMA.
2009 Mar; 301(11):1131-9. doi:
10.1001/jama.301.11.1131. [PMID: 19293413] - M Kotsuma, T Tokui, S Freudenthaler, K Nishimura. Effect of CYP2D6 polymorphism on pharmacokinetics of a novel ACAT inhibitor, pactimibe and its unique metabolite, R-125528.
International journal of clinical pharmacology and therapeutics.
2008 Nov; 46(11):545-55. doi:
10.5414/cpp46545. [PMID: 19000552] - Kenji Takahashi, Masayasu Kasai, Masaru Ohta, Yoshimichi Shoji, Kazuyoshi Kunishiro, Mamoru Kanda, Kazuyoshi Kurahashi, Hiroaki Shirahase. Novel indoline-based acyl-CoA:cholesterol acyltransferase inhibitor with antiperoxidative activity: improvement of physicochemical properties and biological activities by introduction of carboxylic acid.
Journal of medicinal chemistry.
2008 Aug; 51(15):4823-33. doi:
10.1021/jm800248r. [PMID: 18620381] - Masakatsu Kotsuma, Taro Tokui, Stefan Freudenthaler, Kenji Nishimura. Effects of ketoconazole and quinidine on pharmacokinetics of pactimibe and its plasma metabolite, R-125528, in humans.
Drug metabolism and disposition: the biological fate of chemicals.
2008 Aug; 36(8):1505-11. doi:
10.1124/dmd.108.021394. [PMID: 18448569] - Masakatsu Kotsuma, Taro Tokui, Tomoko Ishizuka-Ozeki, Tomoyo Honda, Haruo Iwabuchi, Takahiro Murai, Toshihiko Ikeda, Hideo Saji. CYP2D6-Mediated metabolism of a novel acyl coenzyme A:cholesterol acyltransferase inhibitor, pactimibe, and its unique plasma metabolite, R-125528.
Drug metabolism and disposition: the biological fate of chemicals.
2008 Mar; 36(3):529-34. doi:
10.1124/dmd.107.018853. [PMID: 18056254] - Naoki Terasaka, Atsuhiro Miyazaki, Naomi Kasanuki, Kayoko Ito, Naoko Ubukata, Tadashi Koieyama, Ken Kitayama, Tatsuo Tanimoto, Naoyuki Maeda, Toshimori Inaba. ACAT inhibitor pactimibe sulfate (CS-505) reduces and stabilizes atherosclerotic lesions by cholesterol-lowering and direct effects in apolipoprotein E-deficient mice.
Atherosclerosis.
2007 Feb; 190(2):239-47. doi:
10.1016/j.atherosclerosis.2006.03.007. [PMID: 16626720] - Ken Kitayama, Teiichiro Koga, Toshimori Inaba, Tomoyuki Fujioka. Multiple mechanisms of hypocholesterolemic action of pactimibe, a novel acyl-coenzyme A:cholesterol acyltransferase inhibitor.
European journal of pharmacology.
2006 Aug; 543(1-3):123-32. doi:
10.1016/j.ejphar.2006.05.036. [PMID: 16814766] - Ken Kitayama, Tatsuo Tanimoto, Teiichiro Koga, Naoki Terasaka, Tomoyuki Fujioka, Toshimori Inaba. Importance of acyl-coenzyme A:cholesterol acyltransferase 1/2 dual inhibition for anti-atherosclerotic potency of pactimibe.
European journal of pharmacology.
2006 Jul; 540(1-3):121-30. doi:
10.1016/j.ejphar.2006.04.022. [PMID: 16730694] - Stephen J Nicholls, Ilke Sipahi, Paul Schoenhagen, Lisa Wisniewski, Tammy Churchill, Timothy Crowe, Marlene Goormastic, Kathy Wolski, E Murat Tuzcu, Steven E Nissen. Intravascular ultrasound assessment of novel antiatherosclerotic therapies: rationale and design of the Acyl-CoA:Cholesterol Acyltransferase Intravascular Atherosclerosis Treatment Evaluation (ACTIVATE) Study.
American heart journal.
2006 Jul; 152(1):67-74. doi:
10.1016/j.ahj.2005.10.025. [PMID: 16824833]
