MK-5172 (BioDeep_00000752266)

   


代谢物信息卡片


Grazoprevir

化学式: C38H50N6O9S (766.3359810000001)
中文名称: 格拉瑞韦
谱图信息: 最多检出来源 () 0%

分子结构信息

SMILES: CC(C)(C)C1C(=O)N2CC(CC2C(=O)NC3(CC3C=C)C(=O)NS(=O)(=O)C4CC4)OC5=NC6=C(C=CC(=C6)OC)N=C5CCCCCC7CC7OC(=O)N1
InChI: InChI=1S/C38H50N6O9S/c1-6-22-19-38(22,35(47)43-54(49,50)25-13-14-25)42-32(45)29-18-24-20-44(29)34(46)31(37(2,3)4)41-36(48)53-30-16-21(30)10-8-7-9-11-27-33(52-24)40-28-17-23(51-5)12-15-26(28)39-27/h6,12,15,17,21-22,24-25,29-31H,1,7-11,13-14,16,18-20H2,2-5H3,(H,41,48)(H,42,45)(H,43,47)/t21-,22-,24-,29+,30-,31-,38-/m1/s1

描述信息

J - Antiinfectives for systemic use > J05 - Antivirals for systemic use > J05A - Direct acting antivirals > J05AP - Antivirals for treatment of hcv infections
D000890 - Anti-Infective Agents > D000900 - Anti-Bacterial Agents > D007769 - Lactams
D000890 - Anti-Infective Agents > D000998 - Antiviral Agents
C471 - Enzyme Inhibitor > C783 - Protease Inhibitor

同义名列表

2 个代谢物同义名

Grazoprevir; MK-5172



数据库引用编号

7 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)

0 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

  • Ping-Chin Lai, Cheng-Hsu Chen, Long-Bin Jeng, Tung-Min Yu, Shang-Feng Tsai, Ming-Ju Wu, Shao-Bin Cheng, Sheng-Shun Yang, Teng-Yu Lee. Grazoprevir/Elbasvir Treatment in Liver or Kidney Transplant Recipients with Genotype 1b Hepatitis C Virus Infection. Antimicrobial agents and chemotherapy. 2022 02; 66(2):e0200321. doi: 10.1128/aac.02003-21. [PMID: 34902265]
  • Jinyu Liu, Min Guo, Lei Ke, Ruxu You. Cost-Effectiveness of Elbasvir/Grazoprevir for the Treatment of Chronic Hepatitis C: A Systematic Review. Frontiers in public health. 2022; 10(?):836986. doi: 10.3389/fpubh.2022.836986. [PMID: 35646774]
  • Kerstin Stein, Albrecht Stoehr, Hartwig Klinker, Gerlinde Teuber, Uwe Naumann, Christine John, Renate Heyne, Yvonne Serfert, Claus Niederau, Stefan Zeuzem, Thomas Berg, Johannes Wiegand. Hepatitis C therapy with grazoprevir/elbasvir and glecaprevir/pibrentasvir in patients with advanced chronic kidney disease: data from the German Hepatitis C-Registry (DHC-R). European journal of gastroenterology & hepatology. 2022 01; 34(1):76-83. doi: 10.1097/meg.0000000000001923. [PMID: 32956186]
  • Feroza Begum, Amit Kumar Srivastava, Upasana Ray. Repurposing nonnucleoside antivirals against SARS-CoV2 NSP12 (RNA dependent RNA polymerase): In silico-molecular insight. Biochemical and biophysical research communications. 2021 09; 571(?):26-31. doi: 10.1016/j.bbrc.2021.07.050. [PMID: 34303192]
  • Syed Hani Abidi, Nahlah Makki Almansour, Daulet Amerzhanov, Khaled S Allemailem, Wardah Rafaqat, Mahmoud A A Ibrahim, Philip la Fleur, Martin Lukac, Syed Ali. Repurposing potential of posaconazole and grazoprevir as inhibitors of SARS-CoV-2 helicase. Scientific reports. 2021 05; 11(1):10290. doi: 10.1038/s41598-021-89724-0. [PMID: 33986405]
  • Hirohito Yoneyama, Asahiro Morishita, Hisakazu Iwama, Koji Fujita, Takahiro Masaki, Joji Tani, Tomoko Tadokoro, Takako Nomura, Teppei Sakamoto, Kyoko Oura, Kei Takuma, Mai Nakahara, Shima Mimura, Akihiro Deguchi, Makoto Oryu, Kunihiko Tsutsui, Takashi Himoto, Kunitada Shimotohno, Takaji Wakita, Hideki Kobara, Tsutomu Masaki. Identification of microRNA associated with the elimination of hepatitis C virus genotype 1b by direct-acting antiviral therapies. Journal of gastroenterology and hepatology. 2021 Apr; 36(4):1126-1135. doi: 10.1111/jgh.15224. [PMID: 32839985]
  • Santosh Kumar Behera, Nazmina Vhora, Darshan Contractor, Amit Shard, Dinesh Kumar, Kiran Kalia, Alok Jain. Computational drug repurposing study elucidating simultaneous inhibition of entry and replication of novel corona virus by Grazoprevir. Scientific reports. 2021 03; 11(1):7307. doi: 10.1038/s41598-021-86712-2. [PMID: 33790352]
  • Eun Sun Jang, Kyung-Ah Kim, Young Seok Kim, In Hee Kim, Byung Seok Lee, Youn Jae Lee, Woo Jin Chung, Sook-Hyang Jeong. Effectiveness and safety of elbasvir/grazoprevir in Korean patients with hepatitis C virus infection: a nationwide real-world study. The Korean journal of internal medicine. 2021 03; 36(Suppl 1):S1-S8. doi: 10.3904/kjim.2019.357. [PMID: 32539296]
  • Kawthar Mohamed, Niloufar Yazdanpanah, Amene Saghazadeh, Nima Rezaei. Computational drug discovery and repurposing for the treatment of COVID-19: A systematic review. Bioorganic chemistry. 2021 01; 106(?):104490. doi: 10.1016/j.bioorg.2020.104490. [PMID: 33261845]
  • Gayatri Nangia, John M Vierling, Paul Kwo, Deborah D Brown, Stephanie O Klopfer, Michael N Robertson, Barbara A Haber, K Rajender Reddy. Safety and tolerability of elbasvir/grazoprevir in chronic hepatitis C virus therapy: Integrated analysis from clinical trials. Journal of viral hepatitis. 2020 11; 27(11):1222-1233. doi: 10.1111/jvh.13357. [PMID: 32594612]
  • Deep Bhowmik, Rajat Nandi, Rahul Jagadeesan, Niranjan Kumar, Amresh Prakash, Diwakar Kumar. Identification of potential inhibitors against SARS-CoV-2 by targeting proteins responsible for envelope formation and virion assembly using docking based virtual screening, and pharmacokinetics approaches. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases. 2020 10; 84(?):104451. doi: 10.1016/j.meegid.2020.104451. [PMID: 32640381]
  • Daniëlle W M Pijnenburg, Minou van Seyen, Evertine J Abbink, Angela Colbers, Joost P H Drenth, David M Burger. Pharmacokinetic similarity demonstrated after crushing of the elbasvir/grazoprevir fixed-dose combination tablet for HCV infection. The Journal of antimicrobial chemotherapy. 2020 09; 75(9):2661-2665. doi: 10.1093/jac/dkaa230. [PMID: 32544221]
  • Hafsa Iftikhar, Hafiza Nayyer Ali, Sadia Farooq, Hammad Naveed, Syed Shahzad-Ul-Hussan. Identification of potential inhibitors of three key enzymes of SARS-CoV2 using computational approach. Computers in biology and medicine. 2020 07; 122(?):103848. doi: 10.1016/j.compbiomed.2020.103848. [PMID: 32658735]
  • Anders Boyd, Patrick Miailhes, Julie Chas, Marc-Antoine Valantin, Yazdan Yazdanpanah, Eric Rosenthal, Stephane Chevaliez, Lionel Piroth, Hayette Rougier, Gilles Peytavin, Gilles Pialoux, Pierre-Marie Girard, Karine Lacombe. Grazoprevir/elbasvir for the immediate treatment of recently acquired HCV genotype 1 or 4 infection in MSM. The Journal of antimicrobial chemotherapy. 2020 07; 75(7):1961-1968. doi: 10.1093/jac/dkaa091. [PMID: 32306039]
  • Dorota Zarębska-Michaluk, Jerzy Jaroszewicz, Iwona Buczyńska, Krzysztof Simon, Beata Lorenc, Magdalena Tudrujek-Zdunek, Krzysztof Tomasiewicz, Marek Sitko, Aleksander Garlicki, Ewa Janczewska, Dorota Dybowska, Waldemar Halota, Małgorzata Pawłowska, Paweł Pabjan, Włodzimierz Mazur, Agnieszka Czauż-Andrzejuk, Hanna Berak, Andrzej Horban, Łukasz Socha, Jakub Klapaczyński, Anna Piekarska, Maria Blaszkowska, Teresa Belica-Wdowik, Beata Dobracka, Olga Tronina, Zbigniew Deroń, Jolanta Białkowska-Warzecha, Łukasz Laurans, Robert Flisiak. Real-world experience with Grazoprevir/Elbasvir in the treatment of previously 'difficult to treat' patients infected with hepatitis C virus genotype 1 and 4. Journal of gastroenterology and hepatology. 2020 Jul; 35(7):1238-1246. doi: 10.1111/jgh.14936. [PMID: 31734959]
  • Yi-Chung Hsieh, Chih-Lang Lin, Chao-Hung Hung, Chien-Hung Chen, Shui-Yi Tung, Chun-Yen Lin, Tsung-Hui Hu, Sheng-Nan Lu, Rong-Nan Chien, I-Shyan Sheen. Real-world experience of elbasvir/grazoprevir in Taiwan: This study was focused on liver and renal adverse effects. Journal of viral hepatitis. 2020 05; 27(5):505-513. doi: 10.1111/jvh.13262. [PMID: 32039536]
  • Debra T Choi, Amy Puenpatom, Xian Yu, Kevin F Erickson, Fasiha Kanwal, Hashem B El-Serag, Jennifer R Kramer. Effectiveness of Elbasvir/Grazoprevir in patients with hepatitis C virus genotype 1 infection and chronic kidney disease in the United States veterans population. Antiviral research. 2020 02; 174(?):104698. doi: 10.1016/j.antiviral.2019.104698. [PMID: 31862503]
  • Maneerat Chayanupatkul, Salyavit Chittmittraprap, Pornpitra Pratedrat, Natthaya Chuaypen, Anchalee Avihingsanon, Pisit Tangkijvanich. Efficacy of elbasvir/grazoprevir therapy in HCV genotype-1 with or without HIV infection: role of HCV core antigen monitoring and improvement of liver stiffness and steatosis. Antiviral therapy. 2020; 25(6):305-314. doi: 10.3851/imp3370. [PMID: 32910788]
  • Ezequiel Ridruejo, Rebeca Garcia-Agudo, Manuel Mendizabal, Sami Aoufi-Rabih, Vivek Dixit, Marcelo Silva, Fabrizio Fabrizi. Efficacy and safety of direct-acting antiviral agents for HCV in mild-to-moderate chronic kidney disease. Nefrologia. 2020 Jan; 40(1):46-52. doi: 10.1016/j.nefro.2019.03.013. [PMID: 31229261]
  • Chizoba Nwankwo, Shelby L Corman, Elamin H Elbasha. Projected impact of elbasvir/grazoprevir in patients with hepatitis C virus genotype 1 and chronic kidney disease in Vietnam. Journal of infection and public health. 2019 Jul; 12(4):502-508. doi: 10.1016/j.jiph.2019.01.054. [PMID: 30711348]
  • Luzelena Caro, Larissa Wenning, Hwa-Ping Feng, Zifang Guo, Lihong Du, Pratik Bhagunde, Christine Fandozzi, Deborah Panebianco, William L Marshall, Joan R Butterton, Marian Iwamoto, Wendy W Yeh. Pharmacokinetics of elbasvir and grazoprevir in subjects with end-stage renal disease or severe renal impairment. European journal of clinical pharmacology. 2019 May; 75(5):665-675. doi: 10.1007/s00228-018-2585-3. [PMID: 30680407]
  • Eiichi Ogawa, Norihiro Furusyo, Koichi Azuma, Makoto Nakamuta, Hideyuki Nomura, Kazufumi Dohmen, Takeaki Satoh, Akira Kawano, Toshimasa Koyanagi, Aritsune Ooho, Kazuhiro Takahashi, Masaki Kato, Shinji Shimoda, Eiji Kajiwara, Jun Hayashi. Elbasvir plus grazoprevir for patients with chronic hepatitis C genotype 1: A multicenter, real-world cohort study focusing on chronic kidney disease. Antiviral research. 2018 11; 159(?):143-152. doi: 10.1016/j.antiviral.2018.10.003. [PMID: 30300717]
  • Benedetto Caroleo, Lidia Colangelo, Maria Perticone, Giovambattista De Sarro, Luca Gallelli. Efficacy and Safety of Elbasvir-Grazoprevir Fixed Dose in the Management of Polytreated HCV Patients: Evidence From Real-Life Clinical Practice. Journal of clinical pharmacology. 2018 10; 58(10):1248-1253. doi: 10.1002/jcph.1135. [PMID: 29746724]
  • J E Yap, P Jaiswal, L Ton, R Szynkarek, B M Attar, S Gandhi. Successful treatment of chronic hepatitis C infection with crushed elbasvir/grazoprevir administered via a percutaneous endoscopic gastrostomy tube. Journal of clinical pharmacy and therapeutics. 2018 Oct; 43(5):730-732. doi: 10.1111/jcpt.12713. [PMID: 29906312]
  • Hung-Yu Sun, Pin-Nan Cheng, Chiung-Ying Tseng, Wei-Jen Tsai, Yen-Cheng Chiu, Kung-Chia Young. Favouring modulation of circulating lipoproteins and lipid loading capacity by direct antiviral agents grazoprevir/elbasvir or ledipasvir/sofosbuvir treatment against chronic HCV infection. Gut. 2018 07; 67(7):1342-1350. doi: 10.1136/gutjnl-2017-313832. [PMID: 28615303]
  • Vishnu S Potluri, Roy D Bloom. Treating hepatitis C infection in patients with advanced CKD in the real world: time to refocus on what our real treatment goals should be. Kidney international. 2018 07; 94(1):18-21. doi: 10.1016/j.kint.2018.03.018. [PMID: 29933844]
  • M G Rumi, V Occhipinti. Editorial: real-life data confirm efficacy of elbasvir/grazoprevir in HCV patients with severe kidney disease. Alimentary pharmacology & therapeutics. 2018 07; 48(2):226-227. doi: 10.1111/apt.14792. [PMID: 29939410]
  • S L Flamm. Editorial: real-life data confirm efficacy of elbasvir/grazoprevir in HCV patients with severe kidney disease-Author's reply. Alimentary pharmacology & therapeutics. 2018 07; 48(2):227. doi: 10.1111/apt.14826. [PMID: 29939409]
  • William L Marshall, Hwa-Ping Feng, Larissa Wenning, Graigory Garrett, Xiaobi Huang, Fang Liu, Deborah Panebianco, Luzelena Caro, Christine Fandozzi, Kenneth C Lasseter, Richard A Preston, Thomas Marbury, Joan R Butterton, Marian Iwamoto, Wendy W Yeh. Pharmacokinetics, Safety, and Tolerability of Single-Dose Elbasvir in Participants with Hepatic Impairment. European journal of drug metabolism and pharmacokinetics. 2018 Jun; 43(3):321-329. doi: 10.1007/s13318-017-0451-9. [PMID: 29247332]
  • Christine M Durand, Mary G Bowring, Diane M Brown, Michael A Chattergoon, Guido Massaccesi, Nichole Bair, Russell Wesson, Ashraf Reyad, Fizza F Naqvi, Darin Ostrander, Jeremy Sugarman, Dorry L Segev, Mark Sulkowski, Niraj M Desai. Direct-Acting Antiviral Prophylaxis in Kidney Transplantation From Hepatitis C Virus-Infected Donors to Noninfected Recipients: An Open-Label Nonrandomized Trial. Annals of internal medicine. 2018 04; 168(8):533-540. doi: 10.7326/m17-2871. [PMID: 29507971]
  • Fabrizio Fabrizi, Francesco Negro, Mark Bondin, Patrice Cacoub. Expert opinion on the management of renal manifestations of chronic HCV infection. Antiviral therapy. 2018; 23(Suppl 2):57-67. doi: 10.3851/imp3247. [PMID: 30451153]
  • Kenichi Morikawa, Akihisa Nakamura, Tomoe Shimazaki, Naoya Sakamoto. Safety and efficacy of elbasvir/grazoprevir for the treatment of chronic hepatitis C: current evidence. Drug design, development and therapy. 2018; 12(?):2749-2756. doi: 10.2147/dddt.s133697. [PMID: 30233138]
  • Franck Maunoury, Aurore Clément, Chizoba Nwankwo, Laurie Levy-Bachelot, Armand Abergel, Vincent Di Martino, Eric Thervet, Isabelle Durand-Zaleski. Cost-effectiveness analysis of elbasvir-grazoprevir regimen for treating hepatitis C virus genotype 1 infection in stage 4-5 chronic kidney disease patients in France. PloS one. 2018; 13(3):e0194329. doi: 10.1371/journal.pone.0194329. [PMID: 29543897]
  • Annette Bruchfeld, David Roth, Paul Martin, David R Nelson, Stanislas Pol, Maria-Carlota Londoño, Howard Monsour, Marcelo Silva, Peggy Hwang, Jean-Marie Arduino, Michael Robertson, Bach-Yen Nguyen, Janice Wahl, Eliav Barr, Wayne Greaves. Elbasvir plus grazoprevir in patients with hepatitis C virus infection and stage 4-5 chronic kidney disease: clinical, virological, and health-related quality-of-life outcomes from a phase 3, multicentre, randomised, double-blind, placebo-controlled trial. The lancet. Gastroenterology & hepatology. 2017 08; 2(8):585-594. doi: 10.1016/s2468-1253(17)30116-4. [PMID: 28576451]
  • Maria A Sorbera, Michelle L Friedman, Rebecca Cope. New and Emerging Evidence on the Use of Second-Generation Direct Acting Antivirals for the Treatment of Hepatitis C Virus in Renal Impairment. Journal of pharmacy practice. 2017 Jun; 30(3):359-365. doi: 10.1177/0897190016632128. [PMID: 26902648]
  • E Elbasha, W Greaves, D Roth, C Nwankwo. Cost-effectiveness of elbasvir/grazoprevir use in treatment-naive and treatment-experienced patients with hepatitis C virus genotype 1 infection and chronic kidney disease in the United States. Journal of viral hepatitis. 2017 04; 24(4):268-279. doi: 10.1111/jvh.12639. [PMID: 27966249]
  • Lionel Rostaing, Laurent Alric, Nassim Kamar. Use of direct-acting agents for hepatitis C virus-positive kidney transplant candidates and kidney transplant recipients. Transplant international : official journal of the European Society for Organ Transplantation. 2016 Dec; 29(12):1257-1265. doi: 10.1111/tri.12870. [PMID: 27717014]
  • N Gamal, P Andreone. Grazoprevir/elbasvir fixed-dose combination for hepatitis C. Drugs of today (Barcelona, Spain : 1998). 2016 Jul; 52(7):377-85. doi: 10.1358/dot.2016.52.7.2510258. [PMID: 27540596]
  • Laurent Alric, Delphine Bonnet. Grazoprevir + elbasvir for the treatment of hepatitis C virus infection. Expert opinion on pharmacotherapy. 2016; 17(5):735-42. doi: 10.1517/14656566.2016.1161028. [PMID: 26933896]
  • Nimisha Sulejmani, Syed-Mohammed Jafri, Stuart C Gordon. Pharmacodynamics and pharmacokinetics of elbasvir and grazoprevir in the treatment of hepatitis C. Expert opinion on drug metabolism & toxicology. 2016; 12(3):353-61. doi: 10.1517/17425255.2016.1148685. [PMID: 26849059]
  • David Roth, David R Nelson, Annette Bruchfeld, AnnMarie Liapakis, Marcelo Silva, Howard Monsour, Paul Martin, Stanislas Pol, Maria-Carlota Londoño, Tarek Hassanein, Philippe J Zamor, Eli Zuckerman, Shuyan Wan, Beth Jackson, Bach-Yen Nguyen, Michael Robertson, Eliav Barr, Janice Wahl, Wayne Greaves. Grazoprevir plus elbasvir in treatment-naive and treatment-experienced patients with hepatitis C virus genotype 1 infection and stage 4-5 chronic kidney disease (the C-SURFER study): a combination phase 3 study. Lancet (London, England). 2015 Oct; 386(10003):1537-45. doi: 10.1016/s0140-6736(15)00349-9. [PMID: 26456905]
  • Anita Y M Howe, Stuart Black, Stephanie Curry, Steven W Ludmerer, Rong Liu, Richard J O Barnard, William Newhard, Peggy M T Hwang, David Nickle, Christopher Gilbert, Luzelena Caro, Mark J DiNubile, Niloufar Mobashery. Virologic resistance analysis from a phase 2 study of MK-5172 combined with pegylated interferon/ribavirin in treatment-naive patients with hepatitis C virus genotype 1 infection. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2014 Dec; 59(12):1657-65. doi: 10.1093/cid/ciu696. [PMID: 25266289]
  • Vincenzo Summa, Steven W Ludmerer, John A McCauley, Christine Fandozzi, Christine Burlein, Giuliano Claudio, Paul J Coleman, Jillian M Dimuzio, Marco Ferrara, Marcello Di Filippo, Adam T Gates, Donald J Graham, Steven Harper, Daria J Hazuda, Qian Huang, Carolyn McHale, Edith Monteagudo, Vincenzo Pucci, Michael Rowley, Michael T Rudd, Aileen Soriano, Mark W Stahlhut, Joseph P Vacca, David B Olsen, Nigel J Liverton, Steven S Carroll. MK-5172, a selective inhibitor of hepatitis C virus NS3/4a protease with broad activity across genotypes and resistant variants. Antimicrobial agents and chemotherapy. 2012 Aug; 56(8):4161-7. doi: 10.1128/aac.00324-12. [PMID: 22615282]
  • Steven Harper, John A McCauley, Michael T Rudd, Marco Ferrara, Marcello DiFilippo, Benedetta Crescenzi, Uwe Koch, Alessia Petrocchi, M Katharine Holloway, John W Butcher, Joseph J Romano, Kimberly J Bush, Kevin F Gilbert, Charles J McIntyre, Kevin T Nguyen, Emanuela Nizi, Steven S Carroll, Steven W Ludmerer, Christine Burlein, Jillian M DiMuzio, Donald J Graham, Carolyn M McHale, Mark W Stahlhut, David B Olsen, Edith Monteagudo, Simona Cianetti, Claudio Giuliano, Vincenzo Pucci, Nicole Trainor, Christine M Fandozzi, Michael Rowley, Paul J Coleman, Joseph P Vacca, Vincenzo Summa, Nigel J Liverton. Discovery of MK-5172, a Macrocyclic Hepatitis C Virus NS3/4a Protease Inhibitor. ACS medicinal chemistry letters. 2012 Apr; 3(4):332-6. doi: 10.1021/ml300017p. [PMID: 24900473]