Lonafarnib (BioDeep_00000229516)

 

Secondary id: BioDeep_00000015000

human metabolite


代谢物信息卡片


4-(2-{4-[(2R)-6,15-dibromo-13-chloro-4-azatricyclo[9.4.0.0³,⁸]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-yl]piperidin-1-yl}-2-oxoethyl)piperidine-1-carboxamide

化学式: C27H31Br2ClN4O2 (636.0502135999999)
中文名称: 氯那法尼
谱图信息: 最多检出来源 () 0%

分子结构信息

SMILES: C1CN(CCC1CC(=O)N2CCC(CC2)C3C4=C(CCC5=C3N=CC(=C5)Br)C=C(C=C4Br)Cl)C(=O)N
InChI: InChI=1S/C27H31Br2ClN4O2/c28-20-12-19-2-1-18-13-21(30)14-22(29)24(18)25(26(19)32-15-20)17-5-9-33(10-6-17)23(35)11-16-3-7-34(8-4-16)27(31)36/h12-17,25H,1-11H2,(H2,31,36)/t25-/m1/s1

描述信息

A - Alimentary tract and metabolism > A16 - Other alimentary tract and metabolism products > A16A - Other alimentary tract and metabolism products > A16AX - Various alimentary tract and metabolism products
C471 - Enzyme Inhibitor > C2020 - Farnesyl Transferase Inhibitor
D004791 - Enzyme Inhibitors
Lonafarnib (Sch66336) is a potent and orally active farnesyl transferase (FTase) inhibitor. Lonafarnib inhibits the activities of H-ras, K-ras and N-ras with IC50 values of 1.9 nM, 5.2 nM and 2.8 nM, respectively. Lonafarnib also has anti-hepatitis delta virus (HDV) activities.

同义名列表

8 个代谢物同义名

4-(2-{4-[(2R)-6,15-dibromo-13-chloro-4-azatricyclo[9.4.0.0³,⁸]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-yl]piperidin-1-yl}-2-oxoethyl)piperidine-1-carboxamide; 4-(2-(4-(8-Chloro-3,10-dibromo-6,11-dihydro-5H-benzo-(5,6)-cyclohepta(1,2-b)-pyridin-11(R)-yl)-1-piperidinyl)-2-oxo-ethyl)-1-piperidinecarboxamide; (+)4-(2-(4-(8-Chloro-3,10-dibromo-6,11-dihydro-5H-benzo(5,6)cyclohepta(1,2-b)pyridin-11-yl)-1-piperidinyl)-2-oxoethyl)-1-piperidinecarboxamide; Lonafarnibum; Lonafarnib; SCH 66336; Zokinvy; Sch66336



数据库引用编号

10 个数据库交叉引用编号

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)

2 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

  • Ramona Hartinger, Eva-Maria Lederer, Elisa Schena, Giovanna Lattanzi, Karima Djabali. Impact of Combined Baricitinib and FTI Treatment on Adipogenesis in Hutchinson-Gilford Progeria Syndrome and Other Lipodystrophic Laminopathies. Cells. 2023 05; 12(10):. doi: 10.3390/cells12101350. [PMID: 37408186]
  • Ying Zhou, Jia-Jie Yang, Yuan Cheng, Ge-Xuan Feng, Rong-Hui Yang, Yuan Yuan, Li-Yong Wang, Miao Wang, Lu Kong. Loss of Mature Lamin A/C Triggers a Shift in Intracellular Metabolic Homeostasis via AMPKα Activation. Cells. 2022 12; 11(24):. doi: 10.3390/cells11243988. [PMID: 36552752]
  • Cihan Yurdaydin, Onur Keskin, Esra Yurdcu, Aysun Çalişkan, Soner Önem, Fatih Karakaya, Çağdaş Kalkan, Ersin Karatayli, Senem Karatayli, Ingrid Choong, David Apelian, Christopher Koh, Theo Heller, Ramazan Idilman, A Mithat Bozdayi, Jeffrey S Glenn. A phase 2 dose-finding study of lonafarnib and ritonavir with or without interferon alpha for chronic delta hepatitis. Hepatology (Baltimore, Md.). 2022 06; 75(6):1551-1565. doi: 10.1002/hep.32259. [PMID: 34860418]
  • Diane S Aschenbrenner. New Drugs for Rare Disorders. The American journal of nursing. 2021 02; 121(2):27. doi: 10.1097/01.naj.0000734120.60377.79. [PMID: 33497125]
  • Peter Makhov, Ji A Sohn, Ilya G Serebriiskii, Rushaniya Fazliyeva, Vladimir Khazak, Yanis Boumber, Robert G Uzzo, Vladimir M Kolenko. CRISPR/Cas9 genome-wide loss-of-function screening identifies druggable cellular factors involved in sunitinib resistance in renal cell carcinoma. British journal of cancer. 2020 12; 123(12):1749-1756. doi: 10.1038/s41416-020-01087-x. [PMID: 32968206]
  • Christy Gilman, Theo Heller, Christopher Koh. Chronic hepatitis delta: A state-of-the-art review and new therapies. World journal of gastroenterology. 2019 Aug; 25(32):4580-4597. doi: 10.3748/wjg.v25.i32.4580. [PMID: 31528088]
  • C M Gordon, R H Cleveland, K Baltrusaitis, J Massaro, R B D'Agostino, M G Liang, B Snyder, M Walters, X Li, D T Braddock, M E Kleinman, M W Kieran, L B Gordon. Extraskeletal Calcifications in Hutchinson-Gilford Progeria Syndrome. Bone. 2019 08; 125(?):103-111. doi: 10.1016/j.bone.2019.05.008. [PMID: 31077852]
  • Christopher Koh, Ben L Da, Jeffrey S Glenn. HBV/HDV Coinfection: A Challenge for Therapeutics. Clinics in liver disease. 2019 08; 23(3):557-572. doi: 10.1016/j.cld.2019.04.005. [PMID: 31266627]
  • Cihan Yurdaydin, Zaigham Abbas, Maria Buti, Markus Cornberg, Rafael Esteban, Ohad Etzion, Edward J Gane, Robert G Gish, Jeffrey S Glenn, Saeed Hamid, Theo Heller, Christopher Koh, Pietro Lampertico, Yoav Lurie, Michael Manns, Raymundo Parana, Mario Rizzetto, Stephan Urban, Heiner Wedemeyer. Treating chronic hepatitis delta: The need for surrogate markers of treatment efficacy. Journal of hepatology. 2019 05; 70(5):1008-1015. doi: 10.1016/j.jhep.2018.12.022. [PMID: 30982526]
  • Leslie B Gordon, Susan E Campbell, Joseph M Massaro, Ralph B D'Agostino, Monica E Kleinman, Mark W Kieran, Marsha A Moses. Survey of plasma proteins in children with progeria pre-therapy and on-therapy with lonafarnib. Pediatric research. 2018 05; 83(5):982-992. doi: 10.1038/pr.2018.9. [PMID: 29342131]
  • Cihan Yurdaydin, Onur Keskin, Çağdaş Kalkan, Fatih Karakaya, Aysun Çalişkan, Ersin Karatayli, Senem Karatayli, A Mithat Bozdayi, Christopher Koh, Theo Heller, Ramazan Idilman, Jeffrey S Glenn. Optimizing lonafarnib treatment for the management of chronic delta hepatitis: The LOWR HDV-1 study. Hepatology (Baltimore, Md.). 2018 04; 67(4):1224-1236. doi: 10.1002/hep.29658. [PMID: 29152762]
  • Mario Rizzetto. Investigational drugs in development for Hepatitis D. Expert opinion on investigational drugs. 2017 Sep; 26(9):999-1005. doi: 10.1080/13543784.2017.1357695. [PMID: 28730878]
  • Shailima Rampogu, Ayoung Baek, Minky Son, Amir Zeb, Chanin Park, Raj Kumar, Gihwan Lee, Donghwan Kim, Yeonuk Choi, Yeongrae Cho, Yohan Park, Seok Ju Park, Keun Woo Lee. Computational Exploration for Lead Compounds That Can Reverse the Nuclear Morphology in Progeria. BioMed research international. 2017; 2017(?):5270940. doi: 10.1155/2017/5270940. [PMID: 29226142]
  • Mario Rizzetto. Chronic Hepatitis D; at a Standstill?. Digestive diseases (Basel, Switzerland). 2016 ; 34(4):303-7. doi: 10.1159/000444467. [PMID: 27170382]
  • Christopher Koh, Laetitia Canini, Harel Dahari, Xiongce Zhao, Susan L Uprichard, Vanessa Haynes-Williams, Mark A Winters, Gitanjali Subramanya, Stewart L Cooper, Peter Pinto, Erin F Wolff, Rachel Bishop, Ma Ai Thanda Han, Scott J Cotler, David E Kleiner, Onur Keskin, Ramazan Idilman, Cihan Yurdaydin, Jeffrey S Glenn, Theo Heller. Oral prenylation inhibition with lonafarnib in chronic hepatitis D infection: a proof-of-concept randomised, double-blind, placebo-controlled phase 2A trial. The Lancet. Infectious diseases. 2015 Oct; 15(10):1167-1174. doi: 10.1016/s1473-3099(15)00074-2. [PMID: 26189433]
  • X Chen, J M Makarewicz, J A Knauf, L K Johnson, J A Fagin. Transformation by Hras(G12V) is consistently associated with mutant allele copy gains and is reversed by farnesyl transferase inhibition. Oncogene. 2014 Nov; 33(47):5442-9. doi: 10.1038/onc.2013.489. [PMID: 24240680]
  • Shirou Zhou. Theoretical studies on binding and specificity mechanisms of farnesyltransferase (FTase) and geranylgeranyltransferase type-I (GGTase-I) inhibitors by molecular modeling. Combinatorial chemistry & high throughput screening. 2014; 17(6):509-19. doi: 10.2174/1386207317666140120122920. [PMID: 24444014]
  • Joshua D Ochocki, Mark D Distefano. Prenyltransferase Inhibitors: Treating Human Ailments from Cancer to Parasitic Infections. MedChemComm. 2013 Mar; 4(3):476-492. doi: 10.1039/c2md20299a. [PMID: 25530833]
  • Nan Soon Wong, Michael A Morse. Lonafarnib for cancer and progeria. Expert opinion on investigational drugs. 2012 Jul; 21(7):1043-55. doi: 10.1517/13543784.2012.688950. [PMID: 22620979]
  • Carlos Castaneda, Kellen L Meadows, Roxanne Truax, Michael A Morse, Scott H Kaufmann, William P Petros, Yali Zhu, Paul Statkevich, David L Cutler, Herbert I Hurwitz. Phase I and pharmacokinetic study of lonafarnib, SCH 66336, using a 2-week on, 2-week off schedule in patients with advanced solid tumors. Cancer chemotherapy and pharmacology. 2011 Feb; 67(2):455-63. doi: 10.1007/s00280-010-1488-5. [PMID: 20972873]
  • Abdul Hafeez Khan, Alok Prakash, Dinesh Kumar, Anil Kumar Rawat, Rajeev Srivastava, Shipra Srivastava. Virtual screening and pharmacophore studies for ftase inhibitors using Indian plant anticancer compounds database. Bioinformation. 2010 Jul; 5(2):62-6. doi: 10.6026/97320630005062. [PMID: 21346865]
  • Christophe Long, Laurence Marcourt, Roselyne Raux, Bruno David, Christelle Gau, Christophe Menendez, Min Gao, Marie-France Laroche, Philippe Schambel, Clément Delaude, Frédéric Ausseil, Catherine Lavaud, Georges Massiot. Meroterpenes from Dichrostachys cinerea inhibit protein farnesyl transferase activity. Journal of natural products. 2009 Oct; 72(10):1804-15. doi: 10.1021/np900095z. [PMID: 19761234]
  • Y Zhu, P Statkevich, D L Cutler. Effect of food on the pharmacokinetics of lonafarnib (SCH 66336) following single and multiple doses. International journal of clinical pharmacology and therapeutics. 2007 Oct; 45(10):539-47. doi: 10.5414/cpp45539. [PMID: 17966839]
  • Neal E Ready, Alan Lipton, Yali Zhu, Paul Statkevich, Emily Frank, Dolores Curtis, Ronald M Bukowski. Phase I study of the farnesyltransferase inhibitor lonafarnib with weekly paclitaxel in patients with solid tumors. Clinical cancer research : an official journal of the American Association for Cancer Research. 2007 Jan; 13(2 Pt 1):576-83. doi: 10.1158/1078-0432.ccr-06-1262. [PMID: 17255280]
  • M Bayes, X Rabasseda, J R Prous. Gateways to clinical trials. Methods and findings in experimental and clinical pharmacology. 2006 Mar; 28(2):121-42. doi: . [PMID: 16636723]
  • Ebenezer David, Shi-Yong Sun, Edmund K Waller, Jing Chen, Fadlo R Khuri, Sagar Lonial. The combination of the farnesyl transferase inhibitor lonafarnib and the proteasome inhibitor bortezomib induces synergistic apoptosis in human myeloma cells that is associated with down-regulation of p-AKT. Blood. 2005 Dec; 106(13):4322-9. doi: 10.1182/blood-2005-06-2584. [PMID: 16118318]
  • Andrea D Basso, Asra Mirza, Gongjie Liu, Brian J Long, W Robert Bishop, Paul Kirschmeier. The farnesyl transferase inhibitor (FTI) SCH66336 (lonafarnib) inhibits Rheb farnesylation and mTOR signaling. Role in FTI enhancement of taxane and tamoxifen anti-tumor activity. The Journal of biological chemistry. 2005 Sep; 280(35):31101-8. doi: 10.1074/jbc.m503763200. [PMID: 16006564]
  • Eric Winquist, Malcolm J Moore, Kim N Chi, D Scott Ernst, Hal Hirte, Scott North, Jean Powers, Wendy Walsh, Therese Boucher, Robert Patton, Lesley Seymour. A multinomial Phase II study of lonafarnib (SCH 66336) in patients with refractory urothelial cancer. Urologic oncology. 2005 May; 23(3):143-9. doi: 10.1016/j.urolonc.2004.12.012. [PMID: 15907712]
  • Richard R Desrosiers, Marie-Hélène Cusson, Sandra Turcotte, Richard Béliveau. Farnesyltransferase inhibitor SCH-66336 downregulates secretion of matrix proteinases and inhibits carcinoma cell migration. International journal of cancer. 2005 May; 114(5):702-12. doi: 10.1002/ijc.20807. [PMID: 15609318]
  • M Caraglia, A Budillon, P Tagliaferri, M Marra, A Abbruzzese, F Caponigro. Isoprenylation of intracellular proteins as a new target for the therapy of human neoplasms: preclinical and clinical implications. Current drug targets. 2005 May; 6(3):301-23. doi: 10.2174/1389450053765833. [PMID: 15857290]
  • Sarah J O'Meara, B Therese Kinsella. The effect of the farnesyl protein transferase inhibitor SCH66336 on isoprenylation and signalling by the prostacyclin receptor. The Biochemical journal. 2005 Feb; 386(Pt 1):177-89. doi: 10.1042/bj20041290. [PMID: 15469414]
  • Natalie M G M Appels, Maria J van Maanen, Hilde Rosing, Jan H M Schellens, Jos H Beijnen. Quantitative analysis of the farnesyl transferase inhibitor lonafarnib (Sarasartrade mark, SCH66336) in human plasma using high-performance liquid chromatography coupled with tandem mass spectrometry. Rapid communications in mass spectrometry : RCM. 2005; 19(15):2187-92. doi: 10.1002/rcm.2046. [PMID: 15996016]
  • Shi-Yong Sun, Zhongmei Zhou, Ruoxiang Wang, Haian Fu, Fadlo R Khuri. The farnesyltransferase inhibitor Lonafarnib induces growth arrest or apoptosis of human lung cancer cells without downregulation of Akt. Cancer biology & therapy. 2004 Nov; 3(11):1092-8; discussion 1099. doi: 10.4161/cbt.3.11.1176. [PMID: 15467440]
  • Fadlo R Khuri, Bonnie S Glisson, Edward S Kim, Paul Statkevich, Peter F Thall, Michael L Meyers, Roy S Herbst, Reginald F Munden, Craig Tendler, Yali Zhu, Sandra Bangert, Elizabeth Thompson, Charles Lu, Xue-Mei Wang, Dong M Shin, Merrill S Kies, Vali Papadimitrakopoulou, Frank V Fossella, Paul Kirschmeier, W Robert Bishop, Waun Ki Hong. Phase I study of the farnesyltransferase inhibitor lonafarnib with paclitaxel in solid tumors. Clinical cancer research : an official journal of the American Association for Cancer Research. 2004 May; 10(9):2968-76. doi: 10.1158/1078-0432.ccr-03-0412. [PMID: 15131032]
  • Le Wang, Gary T Wang, Xilu Wang, Yunsong Tong, Gerry Sullivan, David Park, Nicholas M Leonard, Qun Li, Jerry Cohen, Wen-Zhen Gu, Haiying Zhang, Joy L Bauch, Clarissa G Jakob, Charles W Hutchins, Vincent S Stoll, Kennan Marsh, Saul H Rosenberg, Hing L Sham, Nan-Horng Lin. Design, synthesis, and biological activity of 4-[(4-cyano-2-arylbenzyloxy)-(3-methyl-3H-imidazol-4-yl)methyl]benzonitriles as potent and selective farnesyltransferase inhibitors. Journal of medicinal chemistry. 2004 Jan; 47(3):612-26. doi: 10.1021/jm030434f. [PMID: 14736242]
  • Johann S de Bono, Anthony W Tolcher, Eric K Rowinsky. Farnesyltransferase inhibitors and their potential in the treatment of breast carcinoma. Seminars in oncology. 2003 Oct; 30(5 Suppl 16):79-92. doi: 10.1053/j.seminoncol.2003.08.010. [PMID: 14613029]
  • Yunsheng Hsieh, Kara Merkle, Ganfeng Wang, Jean-Marc Brisson, Walter A Korfmacher. High-performance liquid chromatography-atmospheric pressure photoionization/tandem mass spectrometric analysis for small molecules in plasma. Analytical chemistry. 2003 Jul; 75(13):3122-7. doi: 10.1021/ac0300082. [PMID: 12964760]
  • Francesco Caponigro, Marina Casale, Jane Bryce. Farnesyl transferase inhibitors in clinical development. Expert opinion on investigational drugs. 2003 Jun; 12(6):943-54. doi: 10.1517/13543784.12.6.943. [PMID: 12783599]
  • Wolfram C Dempke. Farnesyltransferase inhibitors--a novel approach in the treatment of advanced pancreatic carcinomas. Anticancer research. 2003 Mar; 23(2A):813-8. doi: . [PMID: 12820305]
  • F George Njoroge, Bancha Vibulbhan, Patrick Pinto, Corey L Strickland, W Robert Bishop, Paul Kirschmeir, V Girijavallabhan, Ashit K Ganguly. Trihalobenzocycloheptapyridine analogues of Sch 66336 as potent inhibitors of farnesyl protein transferase. Bioorganic & medicinal chemistry. 2003 Jan; 11(1):139-43. doi: 10.1016/s0968-0896(02)00308-5. [PMID: 12467716]
  • A Awada, F A L M Eskens, M Piccart, D L Cutler, A van der Gaast, H Bleiberg, J Wanders, M N Faber, P Statkevich, P Fumoleau, J Verweij. Phase I and pharmacological study of the oral farnesyltransferase inhibitor SCH 66336 given once daily to patients with advanced solid tumours. European journal of cancer (Oxford, England : 1990). 2002 Nov; 38(17):2272-8. doi: 10.1016/s0959-8049(02)00379-9. [PMID: 12441264]
  • Francesco Caponigro. Farnesyl transferase inhibitors: a major breakthrough in anticancer therapy? Naples, 12 April 2002. Anti-cancer drugs. 2002 Sep; 13(8):891-7. doi: 10.1097/00001813-200209000-00016. [PMID: 12394276]
  • S Sharma, N Kemeny, D P Kelsen, D Ilson, E O'Reilly, S Zaknoen, C Baum, P Statkevich, E Hollywood, Y Zhu, L B Saltz. A phase II trial of farnesyl protein transferase inhibitor SCH 66336, given by twice-daily oral administration, in patients with metastatic colorectal cancer refractory to 5-fluorouracil and irinotecan. Annals of oncology : official journal of the European Society for Medical Oncology. 2002 Jul; 13(7):1067-71. doi: 10.1093/annonc/mdf173. [PMID: 12176785]
  • Diana L Brassard, Jessie M English, Michael Malkowski, Paul Kirschmeier, T L Nagabhushan, W Robert Bishop. Inhibitors of farnesyl protein transferase and MEK1,2 induce apoptosis in fibroblasts transformed with farnesylated but not geranylgeranylated H-Ras. Experimental cell research. 2002 Feb; 273(2):138-46. doi: 10.1006/excr.2001.5440. [PMID: 11822869]
  • F A Eskens, A Awada, D L Cutler, M J de Jonge, G P Luyten, M N Faber, P Statkevich, A Sparreboom, J Verweij, A R Hanauske, M Piccart. Phase I and pharmacokinetic study of the oral farnesyl transferase inhibitor SCH 66336 given twice daily to patients with advanced solid tumors. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2001 Feb; 19(4):1167-75. doi: 10.1200/jco.2001.19.4.1167. [PMID: 11181683]
  • G G Wu, Y Wong, M Poirier. Novel 2,2-bipyridine ligand for palladium-catalyzed regioselective carbonylation. Organic letters. 1999 Sep; 1(5):745-7. doi: 10.1021/ol990123s. [PMID: 16118877]
  • H Kim, P Likhari, C C Lin, A A Nomeir. High-performance liquid chromatographic analysis of the anti-tumor agent SCH 66336 in cynomolgus monkey plasma and evaluation of its chiral inversion in animals. Journal of chromatography. B, Biomedical sciences and applications. 1999 May; 728(1):133-41. doi: 10.1016/s0378-4347(99)00070-5. [PMID: 10379665]
  • F G Njoroge, A G Taveras, J Kelly, S Remiszewski, A K Mallams, R Wolin, A Afonso, A B Cooper, D F Rane, Y T Liu, J Wong, B Vibulbhan, P Pinto, J Deskus, C S Alvarez, J del Rosario, M Connolly, J Wang, J Desai, R R Rossman, W R Bishop, R Patton, L Wang, P Kirschmeier, A K Ganguly. (+)-4-[2-[4-(8-Chloro-3,10-dibromo-6,11-dihydro-5H-benzo[5, 6]cyclohepta[1,2-b]- pyridin-11(R)-yl)-1-piperidinyl]-2-oxo-ethyl]-1-piperidinecarboxamid e (SCH-66336): a very potent farnesyl protein transferase inhibitor as a novel antitumor agent. Journal of medicinal chemistry. 1998 Nov; 41(24):4890-902. doi: 10.1021/jm980462b. [PMID: 9822558]