Herkinorin

Herkinorin
(IUPAC) ime
	(2S,4aR,6aR,7R,9S,10aS,10bR)-9-(benzoiloksi)-2-(3-furanil)dodekahidro -6a,10b-dimetil-4,10-diokso-2H-nafto-[2,1-c]piran-7-karboksilno kiselinski metil estar
Klinički podaci
Identifikatori
ATC kod	nije dodeljen
PubChem	11431898
ChemSpider	9606773
ChEMBL	CHEMBL363324
Hemijski podaci
Formula	C28H30O8
Mol. masa	494,55 g/mol
SMILES	eMolekuli & PubHem
InChI
	InChI=1S/C28H30O8/c1-27-11-9-18-26(32)36-21(17-10-12-34-15-17)14-28(18,2)23(27)22(29)20(13-19(27)25(31)33-3)35-24(30)16-7-5-4-6-8-16/h4-8,10,12,15,18-21,23H,9,11,13-14H2,1-3H3/t18-,19-,20-,21-,23-,27-,28-/m0/s1 ; Key: PYDQMXRFUVDCHC-XAGHGKQISA-N
Farmakoinformacioni podaci
Trudnoća	?
Pravni status	Legalan

Herkinorin je opioidni analgetik koji je analog prirodnog proizvoda Salvinorina A. On je otkriven 2005 tokom ispitivanja odnosa strukture i aktivnosti neoklerodan diterpena, familije hemijskih jedinjenja kojoj pripada Salvinorin A.^[5]

Za razliku od salvinorina A koji je selektivni κ-opioidni agonist bez znatnog afiniteta za μ-opioidni receptor, herkinorin je μ-opioidni agonist sa više nego 100x većim μ-opioidnim afinitetom i 50x nižim κ-opioidnim afinitetom u poređenju sa salvinorinom A.^[6]^[7] Herkinorin je semisintetičko jedinjenje, nastalo od salvinorina B, koji nastaje deacetilacijom salvinorina A. Dok su oba jedinjenja, salvinorin A i salvinorin B, nađena u biljci Salvia divinorum, salvinorin A je prisutan u većim količinama.^[8]

Ispitivanja na primatima su pokazala da on deluje kao periferno aktivni μ i κ agonist sa brzim početkom dejstva.^[9] Za razliku od većine μ-opioidnih agonista, herkinorin ne promoviše regrutovanje β-arestina-2 na intracelularni domen μ-opioidnog receptora, niti indukuje internalizaciju receptora.^[10] To znači da herkinorin možda ne proizvodi toleranciju i zavisnost za razliku od drugih opioida, mada je razvoj tolerancije putem drugih mehanizama bio zapažen,^[11] i neki drugi analozi srodni herkinorinu mogu da regrutuju β-arestine.^[12]

Povezano

Literatura

↑ Li Q, Cheng T, Wang Y, Bryant SH (2010). „PubChem as a public resource for drug discovery.”. Drug Discov Today 15 (23-24): 1052-7. DOI:10.1016/j.drudis.2010.10.003. PMID 20970519. edit
↑ Evan E. Bolton, Yanli Wang, Paul A. Thiessen, Stephen H. Bryant (2008). „Chapter 12 PubChem: Integrated Platform of Small Molecules and Biological Activities”. Annual Reports in Computational Chemistry 4: 217-241. DOI:10.1016/S1574-1400(08)00012-1.
↑ Hettne KM, Williams AJ, van Mulligen EM, Kleinjans J, Tkachenko V, Kors JA. (2010). „Automatic vs. manual curation of a multi-source chemical dictionary: the impact on text mining”. J Cheminform 2 (1): 3. DOI:10.1186/1758-2946-2-3. PMID 20331846. edit
↑ Gaulton A, Bellis LJ, Bento AP, Chambers J, Davies M, Hersey A, Light Y, McGlinchey S, Michalovich D, Al-Lazikani B, Overington JP. (2012). „ChEMBL: a large-scale bioactivity database for drug discovery”. Nucleic Acids Res 40 (Database issue): D1100-7. DOI:10.1093/nar/gkr777. PMID 21948594. edit
↑ [1] Harding WW, Tidgewell K, Byrd N, Cobb H, Dersch CM, Butelman ER, Rothman RB, Prisinzano TE. "Neoclerodane diterpenes as a novel scaffold for mi opioid receptor ligands." Journal of Medicinal Chemistry. 2005 Jul 28;48(15):4765-71. PMID 16033256
↑ [2] Tidgewell K, Harding WW, Lozama A, Cobb H, Shah K, Kannan P, Dersch CM, Parrish D, Deschamps JR, Rothman RB, Prisinzano TE. "Synthesis of salvinorin A analogues as opioid receptor probes." Journal of Natural Products. 2006 Jun;69(6):914-8. PMID 16792410
↑ [3] Holden KG, Tidgewell K, Marquam A, Rothman RB, Navarro H, Prisinzano TE. Synthetic studies of neoclerodane diterpenes from Salvia divinorum: Exploration of the 1-position. Bioorganic and Medicinal Chemistry Letters. 2007 Nov 15;17(22):6111-5. PMID 17904842
↑ [4] Tidgewell K, Harding WW, Schmidt M, Holden KG, Murry DJ, Prisinzano TE. "A facile method for the preparation of deuterium labeled salvinorin A: synthesis of [2,2,2-2H3]-salvinorin A." Bioorganic and Medicinal Chemistry Letters. 2004; 14: 5099-5102. PMID 15380207
↑ Butelman ER, Rus S, Simpson DS, Wolf A, Prisinzano TE, Kreek MJ (October 2008). „The effects of herkinorin, the first mu-selective ligand from a salvinorin A-derived scaffold, in a neuroendocrine biomarker assay in nonhuman primates”. The Journal of Pharmacology and Experimental Therapeutics 327 (1): 154–60. DOI:10.1124/jpet.108.140079. PMC 2614932. PMID 18593955.
↑ [5] Groer CE, Tidgewell K, Moyer RA, Harding WW, Rothman RB, Prisinzano TE, Bohn LM. "An opioid agonist that does not induce μ-opioid receptor--arrestin interactions or receptor internalization." Molecular Pharmacology. 2007 Feb;71(2):549-57. PMID 17090705
↑ [6] Xu H, Partilla JS, Wang X, Rutherford JM, Tidgewell K, Prisinzano TE, Bohn LM, Rothman RB. "A comparison of noninternalizing (herkinorin) and internalizing (DAMGO) mu-opioid agonists on cellular markers related to opioid tolerance and dependence." Synapse. 2007 Mar;61(3):166-75. PMID 17152090
↑ Tidgewell K, Groer CE, Harding WW, Lozama A, Schmidt M, Marquam A, Hiemstra J, Partilla JS, Dersch CM, Rothman RB, Bohn LM, Prisinzano TE (April 2008). „Herkinorin analogues with differential beta-arrestin-2 interactions”. Journal of Medicinal Chemistry 51 (8): 2421–31. DOI:10.1021/jm701162g. PMC 2494883. PMID 18380425.

Vanjske veze

	Portal Medicina
	Portal Hemija

[1] Li Q, Cheng T, Wang Y, Bryant SH (2010). „PubChem as a public resource for drug discovery.”. Drug Discov Today 15 (23-24): 1052-7. DOI:10.1016/j.drudis.2010.10.003. PMID 20970519. edit

[2] Evan E. Bolton, Yanli Wang, Paul A. Thiessen, Stephen H. Bryant (2008). „Chapter 12 PubChem: Integrated Platform of Small Molecules and Biological Activities”. Annual Reports in Computational Chemistry 4: 217-241. DOI:10.1016/S1574-1400(08)00012-1.

[3] Hettne KM, Williams AJ, van Mulligen EM, Kleinjans J, Tkachenko V, Kors JA. (2010). „Automatic vs. manual curation of a multi-source chemical dictionary: the impact on text mining”. J Cheminform 2 (1): 3. DOI:10.1186/1758-2946-2-3. PMID 20331846. edit

[4] Gaulton A, Bellis LJ, Bento AP, Chambers J, Davies M, Hersey A, Light Y, McGlinchey S, Michalovich D, Al-Lazikani B, Overington JP. (2012). „ChEMBL: a large-scale bioactivity database for drug discovery”. Nucleic Acids Res 40 (Database issue): D1100-7. DOI:10.1093/nar/gkr777. PMID 21948594. edit

[5] [1] Harding WW, Tidgewell K, Byrd N, Cobb H, Dersch CM, Butelman ER, Rothman RB, Prisinzano TE. "Neoclerodane diterpenes as a novel scaffold for mi opioid receptor ligands." Journal of Medicinal Chemistry. 2005 Jul 28;48(15):4765-71. PMID 16033256

[6] [2] Tidgewell K, Harding WW, Lozama A, Cobb H, Shah K, Kannan P, Dersch CM, Parrish D, Deschamps JR, Rothman RB, Prisinzano TE. "Synthesis of salvinorin A analogues as opioid receptor probes." Journal of Natural Products. 2006 Jun;69(6):914-8. PMID 16792410

[7] [3] Holden KG, Tidgewell K, Marquam A, Rothman RB, Navarro H, Prisinzano TE. Synthetic studies of neoclerodane diterpenes from Salvia divinorum: Exploration of the 1-position. Bioorganic and Medicinal Chemistry Letters. 2007 Nov 15;17(22):6111-5. PMID 17904842

[8] [4] Tidgewell K, Harding WW, Schmidt M, Holden KG, Murry DJ, Prisinzano TE. "A facile method for the preparation of deuterium labeled salvinorin A: synthesis of [2,2,2-2H3]-salvinorin A." Bioorganic and Medicinal Chemistry Letters. 2004; 14: 5099-5102. PMID 15380207

[pmid18593955-9] Butelman ER, Rus S, Simpson DS, Wolf A, Prisinzano TE, Kreek MJ (October 2008). „The effects of herkinorin, the first mu-selective ligand from a salvinorin A-derived scaffold, in a neuroendocrine biomarker assay in nonhuman primates”. The Journal of Pharmacology and Experimental Therapeutics 327 (1): 154–60. DOI:10.1124/jpet.108.140079. PMC 2614932. PMID 18593955.

[10] [5] Groer CE, Tidgewell K, Moyer RA, Harding WW, Rothman RB, Prisinzano TE, Bohn LM. "An opioid agonist that does not induce μ-opioid receptor--arrestin interactions or receptor internalization." Molecular Pharmacology. 2007 Feb;71(2):549-57. PMID 17090705

[11] [6] Xu H, Partilla JS, Wang X, Rutherford JM, Tidgewell K, Prisinzano TE, Bohn LM, Rothman RB. "A comparison of noninternalizing (herkinorin) and internalizing (DAMGO) mu-opioid agonists on cellular markers related to opioid tolerance and dependence." Synapse. 2007 Mar;61(3):166-75. PMID 17152090

[pmid18380425-12] Tidgewell K, Groer CE, Harding WW, Lozama A, Schmidt M, Marquam A, Hiemstra J, Partilla JS, Dersch CM, Rothman RB, Bohn LM, Prisinzano TE (April 2008). „Herkinorin analogues with differential beta-arrestin-2 interactions”. Journal of Medicinal Chemistry 51 (8): 2421–31. DOI:10.1021/jm701162g. PMC 2494883. PMID 18380425.

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