Abemaciclib (BioDeep_00000175525)
human metabolite blood metabolite
代谢物信息卡片
N-{5-[(4-ethylpiperazin-1-yl)methyl]pyridin-2-yl}-5-fluoro-4-[4-fluoro-2-methyl-1-(propan-2-yl)-1H-1,3-benzodiazol-6-yl]pyrimidin-2-amine
化学式: C27H32F2N8 (506.27178559999993)
中文名称: 阿贝西利
谱图信息:
最多检出来源 Homo sapiens(blood) 11.76%
分子结构信息
SMILES: CCN1CCN(CC1)CC2=CN=C(C=C2)NC3=NC=C(C(=N3)C4=CC5=C(C(=C4)F)N=C(N5C(C)C)C)F
InChI: InChI=1S/C27H32F2N8/c1-5-35-8-10-36(11-9-35)16-19-6-7-24(30-14-19)33-27-31-15-22(29)25(34-27)20-12-21(28)26-23(13-20)37(17(2)3)18(4)32-26/h6-7,12-15,17H,5,8-11,16H2,1-4H3,(H,30,31,33,34)
描述信息
L - Antineoplastic and immunomodulating agents > L01 - Antineoplastic agents > L01E - Protein kinase inhibitors > L01EF - Cyclin-dependent kinase (cdk) inhibitors
C274 - Antineoplastic Agent > C2189 - Signal Transduction Inhibitor > C129824 - Antineoplastic Protein Inhibitor
C471 - Enzyme Inhibitor > C1404 - Protein Kinase Inhibitor > C2185 - Cyclin-Dependent Kinase Inhibitor
C471 - Enzyme Inhibitor > C129825 - Antineoplastic Enzyme Inhibitor
C274 - Antineoplastic Agent > C163758 - Targeted Therapy Agent
同义名列表
6 个代谢物同义名
N-{5-[(4-ethylpiperazin-1-yl)methyl]pyridin-2-yl}-5-fluoro-4-[4-fluoro-2-methyl-1-(propan-2-yl)-1H-1,3-benzodiazol-6-yl]pyrimidin-2-amine; N-{5-[(4-ethylpiperazin-1-yl)methyl]pyridin-2-yl}-5-fluoro-4-(7-fluoro-3-isopropyl-2-methyl-1,3-benzodiazol-5-yl)pyrimidin-2-amine; 5-(4-Ethylpiperazin-1-ylmethyl)pyridin-2-yl)-(5-fluoro-4-(7-fluoro-3-isopropyl-2-methyl-3H-benzimidazol-5-yl)pyrimidin-2-yl)amine; LY-2835219abemaciclib; Abemaciclib; LY2835219
数据库引用编号
7 个数据库交叉引用编号
- PubChem: 46220502
- HMDB: HMDB0247749
- DrugBank: DB12001
- ChEMBL: CHEMBL3301610
- Wikipedia: Abemaciclib
- chemspider: 29340700
- CAS: 1231929-97-7
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
- Zübeyir Huyut, Bünyamin Uçar, Fikret Altındağ, Kenan Yıldızhan, Mehmet Tahir Huyut. Effect of curcumin on lipid profile, fibrosis, and apoptosis in liver tissue in abemaciclib-administered rats.
Drug and chemical toxicology.
2023 Nov; 46(6):1138-1146. doi:
10.1080/01480545.2022.2135007. [PMID: 36259448] - Sen Sun, Lu Liu, Hongming Song, Hong Li. Pharmacokinetic study on the co-administration of abemaciclib and astragaloside IV in rats.
Pharmaceutical biology.
2022 Dec; 60(1):1944-1948. doi:
10.1080/13880209.2022.2125539. [PMID: 36226863] - Alejandra Martínez-Chávez, Nancy H C Loos, Maria C Lebre, Matthijs M Tibben, Hilde Rosing, Jos H Beijnen, Alfred H Schinkel. ABCB1 and ABCG2 limit brain penetration and, together with CYP3A4, total plasma exposure of abemaciclib and its active metabolites.
Pharmacological research.
2022 04; 178(?):105954. doi:
10.1016/j.phrs.2021.105954. [PMID: 34700018] - Jingjing Duan, Zhuo Wang, Ran Duan, Chenxinhui Yang, Ruolin Zhao, Qi Feng, Yuanyuan Qin, Jingwei Jiang, Shouyong Gu, Kaiyan Lv, Libo Zhang, Bixia He, Lutz Birnbaumer, Song Yang, Zhen Chen, Yong Yang. Therapeutic targeting of hepatic ACSL4 ameliorates NASH in mice.
Hepatology (Baltimore, Md.).
2022 01; 75(1):140-153. doi:
10.1002/hep.32148. [PMID: 34510514] - Alejandra Martínez-Chávez, Matthijs M Tibben, Karen A M de Jong, Hilde Rosing, Alfred H Schinkel, Jos H Beijnen. Simultaneous quantification of abemaciclib and its active metabolites in human and mouse plasma by UHPLC-MS/MS.
Journal of pharmaceutical and biomedical analysis.
2021 Sep; 203(?):114225. doi:
10.1016/j.jpba.2021.114225. [PMID: 34242947] - Enaksha R Wickremsinhe, Lisa B Lee. Quantification of abemaciclib and metabolites: evolution of bioanalytical methods supporting a novel oncolytic agent.
Bioanalysis.
2021 May; 13(9):711-724. doi:
10.4155/bio-2021-0039. [PMID: 33870730] - Jing Li, Jun Jiang, Jianmei Wu, Xun Bao, Nader Sanai. Physiologically Based Pharmacokinetic Modeling of Central Nervous System Pharmacokinetics of CDK4/6 Inhibitors to Guide Selection of Drug and Dosing Regimen for Brain Cancer Treatment.
Clinical pharmacology and therapeutics.
2021 02; 109(2):494-506. doi:
10.1002/cpt.2021. [PMID: 32799335] - Akimitsu Maeda, Kei Irie, Naoya Hashimoto, Shoji Fukushima, Hitoshi Ando, Akira Okada, Hiromichi Ebi, Masaki Kajita, Hiroji Iwata, Masataka Sawaki. Serum concentration of the CKD4/6 inhibitor abemaciclib, but not of creatinine, strongly predicts hematological adverse events in patients with breast cancer: a preliminary report.
Investigational new drugs.
2021 02; 39(1):272-277. doi:
10.1007/s10637-020-00994-3. [PMID: 32856274] - Nadia Harbeck. Risk-adapted adjuvant therapy of luminal early breast cancer in 2020.
Current opinion in obstetrics & gynecology.
2021 02; 33(1):53-58. doi:
10.1097/gco.0000000000000679. [PMID: 33337614] - Stefanie L Groenland, Alejandra Martínez-Chávez, Marloes G J van Dongen, Jos H Beijnen, Alfred H Schinkel, Alwin D R Huitema, Neeltje Steeghs. Clinical Pharmacokinetics and Pharmacodynamics of the Cyclin-Dependent Kinase 4 and 6 Inhibitors Palbociclib, Ribociclib, and Abemaciclib.
Clinical pharmacokinetics.
2020 12; 59(12):1501-1520. doi:
10.1007/s40262-020-00930-x. [PMID: 33029704] - P Kellie Turner, Stephen D Hall, Sonya C Chapman, Jessica L Rehmel, Jane E Royalty, Yingying Guo, Palaniappan Kulanthaivel. Abemaciclib Does Not Have a Clinically Meaningful Effect on Pharmacokinetics of CYP1A2, CYP2C9, CYP2D6, and CYP3A4 Substrates in Patients with Cancer.
Drug metabolism and disposition: the biological fate of chemicals.
2020 09; 48(9):796-803. doi:
10.1124/dmd.119.090092. [PMID: 32581049] - Maria M Posada, Bridget L Morse, P Kellie Turner, Palaniappan Kulanthaivel, Stephen D Hall, Gemma L Dickinson. Predicting Clinical Effects of CYP3A4 Modulators on Abemaciclib and Active Metabolites Exposure Using Physiologically Based Pharmacokinetic Modeling.
Journal of clinical pharmacology.
2020 07; 60(7):915-930. doi:
10.1002/jcph.1584. [PMID: 32080863] - Pooja Dhakne, Amit Kumar Sahu, Manish Kumar Sharma, Pinaki Sengupta. Simultaneous quantification of abemaciclib and letrozole in rat plasma: method development, validation and pharmacokinetic application.
Biomedical chromatography : BMC.
2020 Jun; 34(6):e4825. doi:
10.1002/bmc.4825. [PMID: 32166756] - Sara M Tolaney, Andrew M Wardley, Stefania Zambelli, John F Hilton, Tiffany A Troso-Sandoval, Francesco Ricci, Seock-Ah Im, Sung-Bae Kim, Stephen Rd Johnston, Arlene Chan, Shom Goel, Kristen Catron, Sonya C Chapman, Gregory L Price, Zhengyu Yang, M Corona Gainford, Fabrice André. Abemaciclib plus trastuzumab with or without fulvestrant versus trastuzumab plus standard-of-care chemotherapy in women with hormone receptor-positive, HER2-positive advanced breast cancer (monarcHER): a randomised, open-label, phase 2 trial.
The Lancet. Oncology.
2020 06; 21(6):763-775. doi:
10.1016/s1470-2045(20)30112-1. [PMID: 32353342] - Disha Thakkar, Abhijeet S Kate. Update on metabolism of abemaciclib: In silico, in vitro, and in vivo metabolite identification and characterization using high resolution mass spectrometry.
Drug testing and analysis.
2020 Mar; 12(3):331-342. doi:
10.1002/dta.2725. [PMID: 31697023] - Hilary E Nicholson, Zeshan Tariq, Benjamin E Housden, Rebecca B Jennings, Laura A Stransky, Norbert Perrimon, Sabina Signoretti, William G Kaelin. HIF-independent synthetic lethality between CDK4/6 inhibition and VHL loss across species.
Science signaling.
2019 10; 12(601):. doi:
10.1126/scisignal.aay0482. [PMID: 31575731] - Alejandra Martínez-Chávez, Hilde Rosing, Michel Hillebrand, Matthijs Tibben, Alfred H Schinkel, Jos H Beijnen. Development and validation of a bioanalytical method for the quantification of the CDK4/6 inhibitors abemaciclib, palbociclib, and ribociclib in human and mouse matrices using liquid chromatography-tandem mass spectrometry.
Analytical and bioanalytical chemistry.
2019 Aug; 411(20):5331-5345. doi:
10.1007/s00216-019-01932-w. [PMID: 31209549] - Jill C Chappell, P Kellie Turner, Y Anne Pak, James Bacon, Alan Y Chiang, Jane Royalty, Stephen D Hall, Palaniappan Kulanthaivel, Joseph V Bonventre. Abemaciclib Inhibits Renal Tubular Secretion Without Changing Glomerular Filtration Rate.
Clinical pharmacology and therapeutics.
2019 05; 105(5):1187-1195. doi:
10.1002/cpt.1296. [PMID: 30449032] - Edward S Kim, Karen Kelly, Luis G Paz-Ares, Pilar Garrido, Shadia Jalal, Daruka Mahadevan, Martin Gutierrez, Mariano Provencio, Eric Schaefer, Monte Shaheen, Erica L Johnston, P Kellie Turner, Siva Rama Prasad Kambhampati, Richard Beckmann, Anwar Hossain, William J John, Jonathan W Goldman. Abemaciclib in Combination with Single-Agent Options in Patients with Stage IV Non-Small Cell Lung Cancer: A Phase Ib Study.
Clinical cancer research : an official journal of the American Association for Cancer Research.
2018 11; 24(22):5543-5551. doi:
10.1158/1078-0432.ccr-18-0651. [PMID: 30082474] - Niloy Jafar Iqbal, Zhonglei Lu, Shun Mei Liu, Gary J Schwartz, Streamson Chua, Liang Zhu. Cyclin-dependent kinase 4 is a preclinical target for diet-induced obesity.
JCI insight.
2018 09; 3(17):. doi:
10.1172/jci.insight.123000. [PMID: 30185666] - Sonya C Tate, Amanda K Sykes, Palaniappan Kulanthaivel, Edward M Chan, P Kellie Turner, Damien M Cronier. A Population Pharmacokinetic and Pharmacodynamic Analysis of Abemaciclib in a Phase I Clinical Trial in Cancer Patients.
Clinical pharmacokinetics.
2018 03; 57(3):335-344. doi:
10.1007/s40262-017-0559-8. [PMID: 28540640] - Lei Yin, Heng Li, Wenjian Liu, Zhenglin Yao, Zhenzhen Cheng, Huabei Zhang, Hui Zou. A highly potent CDK4/6 inhibitor was rationally designed to overcome blood brain barrier in gliobastoma therapy.
European journal of medicinal chemistry.
2018 Jan; 144(?):1-28. doi:
10.1016/j.ejmech.2017.12.003. [PMID: 29247857] - Amita Patnaik, Lee S Rosen, Sara M Tolaney, Anthony W Tolcher, Jonathan W Goldman, Leena Gandhi, Kyriakos P Papadopoulos, Muralidhar Beeram, Drew W Rasco, John F Hilton, Aejaz Nasir, Richard P Beckmann, Andrew E Schade, Angie D Fulford, Tuan S Nguyen, Ricardo Martinez, Palaniappan Kulanthaivel, Lily Q Li, Martin Frenzel, Damien M Cronier, Edward M Chan, Keith T Flaherty, Patrick Y Wen, Geoffrey I Shapiro. Efficacy and Safety of Abemaciclib, an Inhibitor of CDK4 and CDK6, for Patients with Breast Cancer, Non-Small Cell Lung Cancer, and Other Solid Tumors.
Cancer discovery.
2016 07; 6(7):740-53. doi:
10.1158/2159-8290.cd-16-0095. [PMID: 27217383] - Thomas J Raub, Graham N Wishart, Palaniappan Kulanthaivel, Brian A Staton, Rose T Ajamie, Geri A Sawada, Lawrence M Gelbert, Harlan E Shannon, Concepcion Sanchez-Martinez, Alfonso De Dios. Brain Exposure of Two Selective Dual CDK4 and CDK6 Inhibitors and the Antitumor Activity of CDK4 and CDK6 Inhibition in Combination with Temozolomide in an Intracranial Glioblastoma Xenograft.
Drug metabolism and disposition: the biological fate of chemicals.
2015 Sep; 43(9):1360-71. doi:
10.1124/dmd.114.062745. [PMID: 26149830] - Sonya C Tate, Shufen Cai, Rose T Ajamie, Teresa Burke, Richard P Beckmann, Edward M Chan, Alfonso De Dios, Graham N Wishart, Lawrence M Gelbert, Damien M Cronier. Semi-mechanistic pharmacokinetic/pharmacodynamic modeling of the antitumor activity of LY2835219, a new cyclin-dependent kinase 4/6 inhibitor, in mice bearing human tumor xenografts.
Clinical cancer research : an official journal of the American Association for Cancer Research.
2014 Jul; 20(14):3763-74. doi:
10.1158/1078-0432.ccr-13-2846. [PMID: 24850847]