MK-608

MK-608
داده‌های بالینی
نام‌های دیگر	7-Deaza-2’-C-methyladenosine; 7DMA
وضعیت قانونی
وضعیت قانونی	US: Investigational New Drug ;
شناسه‌ها
	نام آیوپاک (2R,3R,4R,5R)-2-(4-Aminopyrrolo[2,3-d]pyrimidin-7-yl)-5-(hydroxymethyl)-3-methyloxolane-3,4-diol;
شمارهٔ CAS	443642-29-3;
پاب‌کم CID	3011893;
کم‌اسپایدر	2280834;
CompTox Dashboard (EPA)	DTXSID60963208 ;
داده‌های فیزیکی و شیمیایی
فرمول شیمیایی	C12H16N4O4
جرم مولی	۲۸۰٫۲۸۴ g·mol
مدل سه بعدی (جی‌مول)	Interactive image;
	SMILES C[C@]1([C@@H]([C@H](O[C@H]1n2ccc3c2ncnc3N)CO)O)O;
	InChI InChI=1S/C12H16N4O4/c1-12(19)8(18)7(4-17)20-11(12)16-3-2-6-9(13)14-5-15-10(6)16/h2-3,5,7-8,11,17-19H,4H2,1H3,(H2,13,14,15)/t7-,8-,11-,12-/m1/s1; Key:IRZRJANZDIOOIF-GAJNKVMBSA-N;

MK-608 یا ۷-دی‌آزا-۲’-سی-متیل‌آدنوزین (به اختصار: 7DMA) یک داروی ضد ویروس و آنالوگ آدنوزین است. این دارو توسط مرک اند کو. برای درمان هپاتیت سی ساخته شد اما علی‌رغم نتایج خوب در مدل‌های حیوانی، در کارآزمایی‌های بالینی برای انسان ناموفق بود. سپس از آن برای مقاصد پژوهشی استفاده کرد و ثابت شد علیه برخی ویروس‌ها نظیر تب دنگی، انسفالیت ویروسی منتقل‌شونده توسط کنه، پولیوویروس و ویروس زیکا در محیط‌های آزمایشگاهی و مدل‌های حیوانی مؤثر است. به‌دلیل شکست قبلی این ویروس در آزمایش‌های انسانی، بعید است که از آن به‌عنوان یک داروی ضدویروس استفاده شود، اما با توجه به فقدان داروهای مؤثر برای بیماران یادشده، پژوهش‌ها بر روی MK-608 و داروهای مشابه قطع نشده‌است.

جستارهای وابسته

NITD008

منابع

↑ Carroll, S. S.; Ludmerer, S.; Handt, L.; Koeplinger, K.; Zhang, N. R.; Graham, D.; Davies, M.-E.; MacCoss, M.; Hazuda, D.; Olsen, D. B. (2009). "Robust Antiviral Efficacy upon Administration of a Nucleoside Analog to Hepatitis C Virus-Infected Chimpanzees". Antimicrobial Agents and Chemotherapy. 53 (3): 926–934. doi:10.1128/AAC.01032-08. PMC 2650549. PMID 19075052.
↑ Olsen, David B.; Davies, Mary-Ellen; Handt, Larry; Koeplinger, Kenneth; Zhang, Nanyan Rena; Ludmerer, Steven W.; Graham, Donald; Liverton, Nigel; MacCoss, Malcolm; Hazuda, Daria; Carroll, Steven S. (2011). "Sustained Viral Response in a Hepatitis C Virus-Infected Chimpanzee via a Combination of Direct-Acting Antiviral Agents". Antimicrobial Agents and Chemotherapy. 55 (2): 937–939. doi:10.1128/AAC.00990-10. PMC 3028818. PMID 21115793.
↑ Arnold, Jamie J.; Sharma, Suresh D.; Feng, Joy Y.; Ray, Adrian S.; Smidansky, Eric D.; Kireeva, Maria L.; Cho, Aesop; Perry, Jason; Vela, Jennifer E.; Park, Yeojin; Xu, Yili; Tian, Yang; Babusis, Darius; Barauskus, Ona; Peterson, Blake R.; Gnatt, Averell; Kashlev, Mikhail; Zhong, Weidong; Cameron, Craig E. (2012). "Sensitivity of Mitochondrial Transcription and Resistance of RNA Polymerase II Dependent Nuclear Transcription to Antiviral Ribonucleosides". PLOS Pathogens. 8 (11): e1003030. doi:10.1371/journal.ppat.1003030. PMC 3499576. PMID 23166498.
↑ Schul, Wouter; Liu, Wei; Xu, Hao‐Ying; Flamand, Marie; Vasudevan, Subhash G. (2007). "A Dengue Fever Viremia Model in Mice Shows Reduction in Viral Replication and Suppression of the Inflammatory Response after Treatment with Antiviral Drugs". The Journal of Infectious Diseases. 195 (5): 665–674. doi:10.1086/511310. PMID 17262707.
↑ Eyer, Luděk; Valdés, James J.; Gil, Victor A.; Nencka, Radim; Hřebabecký, Hubert; Šála, Michal; Salát, Jiří; Černý, Jiří; Palus, Martin; De Clercq, Erik; Růžek, Daniel (2015). "Nucleoside Inhibitors of Tick-Borne Encephalitis Virus". Antimicrobial Agents and Chemotherapy. 59 (9): 5483–5493. doi:10.1128/AAC.00807-15. PMC 4538560. PMID 26124166.
↑ Goris, Nesya; De Palma, Armando; Toussaint, Jean-François; Musch, Ina; Neyts, Johan; De Clercq, Kris (2007). "2′-C-Methylcytidine as a potent and selective inhibitor of the replication of foot-and-mouth disease virus". Antiviral Research. 73 (3): 161–168. doi:10.1016/j.antiviral.2006.09.007. PMID 17055073.
↑ Wu, Runzhi; Smidansky, Eric D.; Oh, Hyung Suk; Takhampunya, Ratree; Padmanabhan, Radhakrishnan; Cameron, Craig E.; Peterson, Blake R. (2010). "Synthesis of a 6-Methyl-7-deaza Analogue of Adenosine That Potently Inhibits Replication of Polio and Dengue Viruses". Journal of Medicinal Chemistry. 53 (22): 7958–7966. doi:10.1021/jm100593s. PMC 2990348. PMID 20964406.
↑ Eyer, Luděk; Nencka, Radim; Huvarová, Ivana; Palus, Martin; Joao Alves, Maria; Gould, Ernest A.; De Clercq, Erik; Růžek, Daniel (2016). "Nucleoside Inhibitors of Zika Virus". Journal of Infectious Diseases. 214 (5): 707–711. doi:10.1093/infdis/jiw226. PMID 27234417.
↑ Zmurko, Joanna; Marques, Rafael E.; Schols, Dominique; Verbeken, Erik; Kaptein, Suzanne J.F.; Neyts, Johan (2016). "The Viral Polymerase Inhibitor 7-Deaza-2'-C-Methyladenosine is a Potent Inhibitor of in Vitro Zika Virus Replication and Delays Disease Progression in a Robust Mouse Infection Model". PLOS Neglected Tropical Diseases. 10 (5): e0004695. doi:10.1371/journal.pntd.0004695. PMC 4862633. PMID 27163257.
↑ Vittori, S.; Dal Ben, D.; Lambertucci, C.; Marucci, G.; Volpini, R.; Cristalli, G. (2006). "Antiviral Properties of Deazaadenine Nucleoside Derivatives". Current Medicinal Chemistry. 13 (29): 3529–3552. doi:10.2174/092986706779026228. PMID 17168721.

[1] Carroll, S. S.; Ludmerer, S.; Handt, L.; Koeplinger, K.; Zhang, N. R.; Graham, D.; Davies, M.-E.; MacCoss, M.; Hazuda, D.; Olsen, D. B. (2009). "Robust Antiviral Efficacy upon Administration of a Nucleoside Analog to Hepatitis C Virus-Infected Chimpanzees". Antimicrobial Agents and Chemotherapy. 53 (3): 926–934. doi:10.1128/AAC.01032-08. PMC 2650549. PMID 19075052.

[2] Olsen, David B.; Davies, Mary-Ellen; Handt, Larry; Koeplinger, Kenneth; Zhang, Nanyan Rena; Ludmerer, Steven W.; Graham, Donald; Liverton, Nigel; MacCoss, Malcolm; Hazuda, Daria; Carroll, Steven S. (2011). "Sustained Viral Response in a Hepatitis C Virus-Infected Chimpanzee via a Combination of Direct-Acting Antiviral Agents". Antimicrobial Agents and Chemotherapy. 55 (2): 937–939. doi:10.1128/AAC.00990-10. PMC 3028818. PMID 21115793.

[3] Arnold, Jamie J.; Sharma, Suresh D.; Feng, Joy Y.; Ray, Adrian S.; Smidansky, Eric D.; Kireeva, Maria L.; Cho, Aesop; Perry, Jason; Vela, Jennifer E.; Park, Yeojin; Xu, Yili; Tian, Yang; Babusis, Darius; Barauskus, Ona; Peterson, Blake R.; Gnatt, Averell; Kashlev, Mikhail; Zhong, Weidong; Cameron, Craig E. (2012). "Sensitivity of Mitochondrial Transcription and Resistance of RNA Polymerase II Dependent Nuclear Transcription to Antiviral Ribonucleosides". PLOS Pathogens. 8 (11): e1003030. doi:10.1371/journal.ppat.1003030. PMC 3499576. PMID 23166498.

[4] Schul, Wouter; Liu, Wei; Xu, Hao‐Ying; Flamand, Marie; Vasudevan, Subhash G. (2007). "A Dengue Fever Viremia Model in Mice Shows Reduction in Viral Replication and Suppression of the Inflammatory Response after Treatment with Antiviral Drugs". The Journal of Infectious Diseases. 195 (5): 665–674. doi:10.1086/511310. PMID 17262707.

[5] Eyer, Luděk; Valdés, James J.; Gil, Victor A.; Nencka, Radim; Hřebabecký, Hubert; Šála, Michal; Salát, Jiří; Černý, Jiří; Palus, Martin; De Clercq, Erik; Růžek, Daniel (2015). "Nucleoside Inhibitors of Tick-Borne Encephalitis Virus". Antimicrobial Agents and Chemotherapy. 59 (9): 5483–5493. doi:10.1128/AAC.00807-15. PMC 4538560. PMID 26124166.

[6] Goris, Nesya; De Palma, Armando; Toussaint, Jean-François; Musch, Ina; Neyts, Johan; De Clercq, Kris (2007). "2′-C-Methylcytidine as a potent and selective inhibitor of the replication of foot-and-mouth disease virus". Antiviral Research. 73 (3): 161–168. doi:10.1016/j.antiviral.2006.09.007. PMID 17055073.

[7] Wu, Runzhi; Smidansky, Eric D.; Oh, Hyung Suk; Takhampunya, Ratree; Padmanabhan, Radhakrishnan; Cameron, Craig E.; Peterson, Blake R. (2010). "Synthesis of a 6-Methyl-7-deaza Analogue of Adenosine That Potently Inhibits Replication of Polio and Dengue Viruses". Journal of Medicinal Chemistry. 53 (22): 7958–7966. doi:10.1021/jm100593s. PMC 2990348. PMID 20964406.

[8] Eyer, Luděk; Nencka, Radim; Huvarová, Ivana; Palus, Martin; Joao Alves, Maria; Gould, Ernest A.; De Clercq, Erik; Růžek, Daniel (2016). "Nucleoside Inhibitors of Zika Virus". Journal of Infectious Diseases. 214 (5): 707–711. doi:10.1093/infdis/jiw226. PMID 27234417.

[9] Zmurko, Joanna; Marques, Rafael E.; Schols, Dominique; Verbeken, Erik; Kaptein, Suzanne J.F.; Neyts, Johan (2016). "The Viral Polymerase Inhibitor 7-Deaza-2'-C-Methyladenosine is a Potent Inhibitor of in Vitro Zika Virus Replication and Delays Disease Progression in a Robust Mouse Infection Model". PLOS Neglected Tropical Diseases. 10 (5): e0004695. doi:10.1371/journal.pntd.0004695. PMC 4862633. PMID 27163257.

[10] Vittori, S.; Dal Ben, D.; Lambertucci, C.; Marucci, G.; Volpini, R.; Cristalli, G. (2006). "Antiviral Properties of Deazaadenine Nucleoside Derivatives". Current Medicinal Chemistry. 13 (29): 3529–3552. doi:10.2174/092986706779026228. PMID 17168721.