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Revision as of 20:11, 16 February 2012 editBeetstra (talk | contribs)Edit filter managers, Administrators172,074 edits Saving copy of the {{drugbox}} taken from revid 456644274 of page Adjudin for the Chem/Drugbox validation project (updated: 'CAS_number').		Latest revision as of 03:11, 2 November 2024 edit Citation bot (talk | contribs)Bots5,457,019 edits Altered doi-broken-date. | Use this bot. Report bugs. | #UCB_CommandLine
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			{{Short description|Chemical compound}}
	{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid of page ] with values updated to verified values.}}
			{{Use dmy dates|date=September 2022}}
	{{Drugbox		{{Drugbox
			| Verifiedfields = changed
	| verifiedrevid = 450867330		| verifiedrevid = 477242932
	| IUPAC_name = 1-(2,4-dichlorobenzyl)-1H-indazole-3-carbohydrazide		| IUPAC_name = 1-(2,4-dichlorobenzyl)-1H-indazole-3-carbohydrazide
	| image = Adjudin_structure.png		| image = Adjudin Structure.svg
	| width = 180		| width =
	<!--Clinical data-->		<!--Clinical data-->
	| tradename =		| tradename =
	| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->		| pregnancy_AU = <!-- A, B1, B2, B3, C, D, X -->
	| pregnancy_US = <!-- A / B / C / D / X -->		| pregnancy_US = <!-- A, B, C, D, X -->
	| pregnancy_category =		| pregnancy_category =
	| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled-->		| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled-->
	| legal_CA = <!-- Schedule I, II, III, IV, V, VI, VII, VIII -->		| legal_CA = <!-- Schedule I, II, III, IV, V, VI, VII, VIII -->
	| legal_UK = <!-- GSL, P, POM, CD, or Class A, B, C -->		| legal_UK = <!-- GSL, P, POM, CD, or Class A, B, C -->
			| legal_US = Investigational New Drug
	| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
	| legal_status = Investigational new drug		| legal_status =
	| routes_of_administration =		| routes_of_administration =
	<!--Pharmacokinetic data-->		<!--Pharmacokinetic data-->
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	| metabolism =		| metabolism =
	| elimination_half-life =		| elimination_half-life =
	| excretion =		| excretion =
	<!--Identifiers-->		<!--Identifiers-->
	| CAS_number_Ref = {{cascite|correct|??}}		| CAS_number_Ref = {{cascite|correct|CAS}}
	| CAS_number = <!-- blanked - oldvalue: 252025-52-8 -->		| CAS_number = 252025-52-8
			| UNII_Ref = {{fdacite|correct|FDA}}
			| UNII = VZT8V72829
	| ATC_prefix = none		| ATC_prefix = none
	| ATC_suffix =		| ATC_suffix =
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	| chemical_formula =		| chemical_formula =
	| C=15 | H=12 | Cl=2 | N=4 | O=1		| C=15 | H=12 | Cl=2 | N=4 | O=1
	| molecular_weight = 335.188 g/mol
	| smiles = C1=CC=C2C(=C1)C(=NN2CC3=C(C=C(C=C3)Cl)Cl)C(=O)NN		| smiles = C1=CC=C2C(=C1)C(=NN2CC3=C(C=C(C=C3)Cl)Cl)C(=O)NN
	| InChI = 1/C15H12Cl2N4O/c16-10-6-5-9(12(17)7-10)8-21-13-4-2-1-3-11(13)14(20-21)15(22)19-18/h1-7H,8,18H2,(H,19,22)
	| InChIKey = VENCPJAAXKBIJD-UHFFFAOYAB
	| StdInChI_Ref = {{stdinchicite|correct|chemspider}}		| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
	| StdInChI = 1S/C15H12Cl2N4O/c16-10-6-5-9(12(17)7-10)8-21-13-4-2-1-3-11(13)14(20-21)15(22)19-18/h1-7H,8,18H2,(H,19,22)		| StdInChI = 1S/C15H12Cl2N4O/c16-10-6-5-9(12(17)7-10)8-21-13-4-2-1-3-11(13)14(20-21)15(22)19-18/h1-7H,8,18H2,(H,19,22)
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	| StdInChIKey = VENCPJAAXKBIJD-UHFFFAOYSA-N		| StdInChIKey = VENCPJAAXKBIJD-UHFFFAOYSA-N
	}}		}}
			'''Adjudin''' ('''AF-2364''') is a ] which is under development as a potential non-hormonal ] drug, which acts by blocking the production of ] in the ], but without affecting ] production.<ref>{{cite journal | vauthors = Mruk DD | title = New perspectives in non-hormonal male contraception | journal = Trends in Endocrinology and Metabolism | volume = 19 | issue = 2 | pages = 57–64 | date = March 2008 | pmid = 18291665 | doi = 10.1016/j.tem.2007.11.002 | s2cid = 29435757 }}</ref> It is an analogue of the chemotherapy drug ], an indazole-carboxylic acid, and further studies continue to be conducted into this family of drugs as possible contraceptives.<ref>{{cite journal | vauthors = Tash JS, Attardi B, Hild SA, Chakrasali R, Jakkaraj SR, Georg GI | title = A novel potent indazole carboxylic acid derivative blocks spermatogenesis and is contraceptive in rats after a single oral dose | journal = Biology of Reproduction | volume = 78 | issue = 6 | pages = 1127–38 | date = June 2008 | pmid = 18218612 | doi = 10.1095/biolreprod.106.057810 | doi-access = free }}</ref>
			{{asof|2007|5|1}}, adjudin was in phase II human trials.<ref>{{cite journal | title=Male Contraceptive Methods Are in the Pipeline | first = Robert | last = Finn | name-list-style = vanc | journal= Ob.gyn. News| year=2007 | doi=10.1016/S0029-7437(07)70395-6 | url=https://linkinghub.elsevier.com/retrieve/pii/S0029-7437(07)70395-6 | issn=0029-7437|volume=42 | issue=9 | page=28 | doi-broken-date = 1 November 2024 }}</ref>
			As shown in mature male rats, the agent induces reversible ] loss from the seminiferous epithelium by disrupting cell adhesion function between Sertoli and germ cells.<ref>{{cite journal | vauthors = Mruk DD, Cheng CY | title = Sertoli-Sertoli and Sertoli-germ cell interactions and their significance in germ cell movement in the seminiferous epithelium during spermatogenesis | journal = Endocrine Reviews | volume = 25 | issue = 5 | pages = 747–806 | date = October 2004 | pmid = 15466940 | doi = 10.1210/er.2003-0022 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Lee NP, Wong EW, Mruk DD, Cheng CY | title = Testicular cell junction: a novel target for male contraception | journal = Current Medicinal Chemistry | volume = 16 | issue = 7 | pages = 906–15 | year = 2009 | pmid = 19275601 | pmc = 2804911 | doi = 10.2174/092986709787549262 }}</ref> It weakens the adhesion between the ] and maturing ] leading to a sloughing and loss of the latter.<ref>{{cite journal | vauthors = Cheng CY, Mruk D, Silvestrini B, Bonanomi M, Wong CH, Siu MK, Lee NP, Lui WY, Mo MY | display-authors = 6 | title = AF-2364 is a potential male contraceptive: a review of recent data | journal = Contraception | volume = 72 | issue = 4 | pages = 251–61 | date = October 2005 | pmid = 16181968 | doi = 10.1016/j.contraception.2005.03.008 }}</ref> As it does not affect spermatogonia themselves the loss of fertility is reversible. In experiments hormonal levels (], ], ]) were undisturbed during administration, and normal ] returned in 95% of the tubules of rats at 210 days after the drug had been discontinued.<ref>{{cite journal | vauthors = Grima J, Silvestrini B, Cheng CY | title = Reversible inhibition of spermatogenesis in rats using a new male contraceptive, 1-(2,4-dichlorobenzyl)-indazole-3-carbohydrazide | journal = Biology of Reproduction | volume = 64 | issue = 5 | pages = 1500–8 | date = May 2001 | pmid = 11319158 | doi = 10.1095/biolreprod64.5.1500 | doi-access = free }}</ref>
			When taken orally, the drug has very low ]. The oral dose effective for contraception is so high that there have been side effects in the muscles and liver. Coupling an Adjudin molecule to a mutant form of ] may solve this problem.<ref>{{cite journal | vauthors = Mruk DD, Wong CH, Silvestrini B, Cheng CY | title = A male contraceptive targeting germ cell adhesion | journal = Nature Medicine | volume = 12 | issue = 11 | pages = 1323–8 | date = November 2006 | pmid = 17072312 | doi = 10.1038/nm1420 | s2cid = 19460327 | url = https://www.newscientist.com/article/dn10397-future-male-pill-targets-testicles.html }}</ref> The mutant FSH is modified such that it no longer induces ] B production, but the membrane-bound FSH receptors on ] still bind to it, delivering the Adjudin directly to the target cells. The adjudin-FSH can be either injected, delivered in an implant, or as a gel.<ref>{{Cite web |url=http://malecontraceptives.org/methods/adjudin.php |title=Methods. Adjudin |access-date=29 September 2010 |archive-date=11 October 2010 |archive-url=https://web.archive.org/web/20101011035444/http://malecontraceptives.org/methods/adjudin.php |url-status=dead }}</ref>
			A study in 2013 indicated that Adjudin, similar to its analogue ], has properties that inhibit cancer growth by targeting mitochondria and blocking energy metabolism in certain kinds of tumor cells in mice, indicating that it has potential as a drug for ].<ref>{{cite journal | vauthors = Xie QR, Liu Y, Shao J, Yang J, Liu T, Zhang T, Wang B, Mruk DD, Silvestrini B, Cheng CY, Xia W | display-authors = 6 | title = Male contraceptive Adjudin is a potential anti-cancer drug | journal = Biochemical Pharmacology | volume = 85 | issue = 3 | pages = 345–55 | date = February 2013 | pmid = 23178657 | pmc = 4108200 | doi = 10.1016/j.bcp.2012.11.008 }}</ref>
			It was invented by ].<ref>{{cite web|title=Obsessed Scientist Finally Throttles 'Em! Non-Paternity Potion | work= The New York Observer|access-date=2008-09-28|url=http://www.observer.com/node/36309|archive-url=https://web.archive.org/web/20080924221042/http://www.observer.com/node/36309|url-status=dead|archive-date=2008-09-24}}</ref><ref>{{cite web|title=Future male "pill" targets testicles|access-date=2008-09-28|url=https://www.newscientist.com/article/dn10397-future-male-pill-targets-testicles.html}}</ref><ref>{{cite web|url=http://www.sciencebase.com/science-blog/male-pill.html|title=Male pill - Science Base|access-date=2008-09-28}}</ref><ref>{{cite web|url=http://seedmagazine.com/news/2006/10/the_hunt_for_male_birth_contro.php|title=Seed: The Hunt for Male Birth Control|access-date=2008-09-28|archive-url=https://web.archive.org/web/20081002153134/http://www.seedmagazine.com/news/2006/10/the_hunt_for_male_birth_contro.php|archive-date=2008-10-02|url-status=unfit}}</ref>
			== References ==
			{{Reflist|30em}}
			== External links ==
			* at the Independent
			* at BBC News
			* at MaleContraceptives.org
			{{Hydrazines}}
			]
			]
			]
			]
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