Revision as of 01:16, 12 August 2011 editCheMoBot (talk | contribs)Bots141,565 edits Updating {{drugbox}} (no changed fields - added verified revid - updated 'ChemSpiderID_Ref', 'ChEMBL_Ref', 'ChEBI_Ref', 'StdInChI_Ref', 'StdInChIKey_Ref', 'ChEBI_Ref') per Chem/Drugbox validation← Previous edit |
Latest revision as of 11:57, 13 August 2023 edit undoOAbot (talk | contribs)Bots442,978 editsm Open access bot: doi added to citation with #oabot. |
(60 intermediate revisions by 41 users not shown) |
Line 1: |
Line 1: |
|
|
{{Short description|Chemical compound}} |
|
{{drugbox |
|
|
|
{{Drugbox |
|
|
| Verifiedfields = changed |
|
|
| Watchedfields = changed |
|
|
| verifiedrevid = 444364270 |
|
|
| image = Lomitapide_skeletal.svg |
|
|
|
|
|
<!--Clinical data--> |
|
|
| pronounce = |
|
|
| tradename = Juxtapid (US), Lojuxta (EU) |
|
|
| Drugs.com = |
|
|
| MedlinePlus = |
|
|
| licence_EU = yes |
|
|
| DailyMedID = Lomitapide |
|
|
| licence_US = Lomitapide |
|
|
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> |
|
|
| pregnancy_category = |
|
|
| routes_of_administration = ] |
|
|
| ATC_prefix = C10 |
|
|
| ATC_suffix = AX12 |
|
|
| ATC_supplemental = |
|
|
|
|
|
| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled--> |
|
|
| legal_CA = <!-- Schedule I, II, III, IV, V, VI, VII, VIII --> |
|
|
| legal_UK = <!-- GSL, P, POM, CD, or Class A, B, C --> |
|
|
| legal_US = Rx-only |
|
|
| legal_US_comment = <ref name="Juxtapid FDA label">{{cite web | title=Juxtapid- lomitapide mesylate capsule | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e4c45bb5-15f4-437e-ab98-a649b3676d14 | access-date=27 January 2021}}</ref> |
|
|
| legal_EU = Rx-only |
|
|
| legal_EU_comment = <ref name="Lojuxta EPAR" /> |
|
|
| legal_status = |
|
|
|
|
|
<!--Pharmacokinetic data--> |
|
|
| bioavailability = |
|
|
| protein_bound = |
|
|
| metabolism = |
|
|
| elimination_half-life = |
|
|
| excretion = |
|
|
|
|
|
<!--Identifiers--> |
|
|
| index2_label = mesylate |
|
|
| IUPHAR_ligand = 7439 |
|
|
| CAS_number_Ref = {{cascite|correct|??}} |
|
|
| CAS_number = 182431-12-5 |
|
|
| CAS_number2 = 202914-84-9 |
|
|
| PubChem = 9853053 |
|
|
| PubChem2 = 11274333 |
|
|
| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
|
|
| DrugBank = DB08827 |
|
|
| DrugBank2 = DBSALT000110 |
|
|
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} |
|
|
| ChemSpiderID = 8028764 |
|
|
| ChemSpiderID2 = 9449335 |
|
| UNII_Ref = {{fdacite|correct|FDA}} |
|
| UNII_Ref = {{fdacite|correct|FDA}} |
|
| UNII = 82KUB0583F |
|
| UNII = 82KUB0583F |
|
|
| UNII2 = X4S83CP54E |
|
| verifiedrevid = 443292980 |
|
|
| IUPAC_name = <nowiki>N-(2,2,2-Trifluoroethyl)-9-2-yl]carbonyl]amino]-1-piperidinyl]butyl]9H-fluoren-9-carboxamde</nowiki> |
|
|
| image = AEGR-733 structure.svg |
|
|
| CAS_number = 182431-12-5 |
|
|
| CAS_supplemental = <br />{{CAS|202914-84-9}} (]) |
|
|
| ATC_prefix = none |
|
|
| ATC_suffix = |
|
|
| ATC_supplemental = |
|
|
| PubChem = |
|
|
| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
|
|
| DrugBank = |
|
|
| KEGG_Ref = {{keggcite|correct|kegg}} |
|
| KEGG_Ref = {{keggcite|correct|kegg}} |
|
| KEGG = D09637 |
|
| KEGG = D09637 |
|
|
| KEGG2 = D09638 |
|
| synonyms = AEGR-773, BMS-201038 |
|
|
|
| ChEBI_Ref = {{ebicite|changed|EBI}} |
|
| chemical_formula = |
|
|
|
| ChEBI = 72297 |
|
|
| ChEBI2 = 72299 |
|
|
| ChEMBL = 354541 |
|
|
| ChEMBL2 = 2105662 |
|
|
| synonyms = AEGR-773, BMS-201038 |
|
|
|
|
|
<!--Chemical data--> |
|
|
| IUPAC_name = ''N''-(2,2,2-Trifluoroethyl)-9-2-yl]carbonyl]amino]-1-piperidinyl]butyl]-9''H''-fluoren-9-carboxamide |
|
| C=39 | H=37 | F=6 | N=3 | O=2 |
|
| C=39 | H=37 | F=6 | N=3 | O=2 |
|
|
| smiles = FC(F)(F)c5ccc(cc5)-c1ccccc1C(=O)NC4CCN(CC4)CCCCC2(C(=O)NCC(F)(F)F)c3ccccc3-c6ccccc26 |
|
| molecular_weight = 693.719 g/mol |
|
|
|
| StdInChI_Ref = {{stdinchicite|changed|chemspider}} |
|
| smiles = FC(F)(F)c5ccc(cc5)-c1ccccc1C(=O)NC4CCN(CC4)CCCCC2(C(=O)NCC(F)(F)F)c3ccccc3-c6ccccc26 |
|
|
|
| StdInChI = 1S/C39H37F6N3O2/c40-38(41,42)25-46-36(50)37(33-13-5-3-10-30(33)31-11-4-6-14-34(31)37)21-7-8-22-48-23-19-28(20-24-48)47-35(49)32-12-2-1-9-29(32)26-15-17-27(18-16-26)39(43,44)45/h1-6,9-18,28H,7-8,19-25H2,(H,46,50)(H,47,49) |
|
| bioavailability = |
|
|
|
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} |
|
| protein_bound = |
|
|
|
| StdInChIKey = MBBCVAKAJPKAKM-UHFFFAOYSA-N |
|
| metabolism = |
|
|
| elimination_half-life = |
|
|
| excretion = |
|
|
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> |
|
|
| pregnancy_US = <!-- A / B / C / D / X --> |
|
|
| pregnancy_category= |
|
|
| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled--> |
|
|
| legal_CA = <!-- Schedule I, II, III, IV, V, VI, VII, VIII --> |
|
|
| legal_UK = <!-- GSL, P, POM, CD, or Class A, B, C --> |
|
|
| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V --> |
|
|
| legal_status = Investigational |
|
|
| routes_of_administration = Oral |
|
|
}} |
|
}} |
|
|
|
|
|
'''Lomitapide''' (]) is an investigational drug for the treatment of ], developed by ].<ref name="Spreitzer">{{cite journal |
|
'''Lomitapide''' , sold under the brand name '''Juxtapid''' in the US and '''Lojuxta ''' in the EU, is a medication used as a ] for the treatment of ], developed by Aegerion Pharmaceuticals.<ref name="Spreitzer">{{cite journal |
|
| author = H. Spreitzer |
|
| author = H. Spreitzer |
|
| date = 12 March 2007 |
|
| date = 12 March 2007 |
|
| title = Neue Wirkstoffe – BMS-201038 |
|
| title = Neue Wirkstoffe – BMS-201038 |
|
| journal = Österreichische Apothekerzeitung |
|
| journal = Österreichische Apothekerzeitung |
|
| issue = 6/2007 |
|
| issue = 6/2007 |
|
| pages = 268 |
|
| pages = 268 |
|
| language = German |
|
| language = German |
|
|
}}</ref> It has been tested in ] as single treatment and in combinations with ], ] and ].<ref>{{cite journal | vauthors = Horwich TB, Fonarow GC | title = Measures of obesity and outcomes after myocardial infarction | journal = Circulation | volume = 118 | issue = 5 | pages = 469–71 | date = July 2008 | pmid = 18663098 | doi = 10.1161/CIRCULATIONAHA.108.792689 | doi-access = free }}</ref><ref>{{cite web | url = http://www.pr-inside.com/aegerion-pharmaceuticals-inc-announces-aegr-r904473.htm | title = Aegerion Pharmaceuticals, Inc. Announces AEGR-733 Phase II Data Demonstrates Significant Lowering of LDL Cholesterol with Promising Hepatic Safety Profile | work = Business Wire | date = 9 November 2008 | archive-url = https://web.archive.org/web/20120229092512/http://www.pr-inside.com/aegerion-pharmaceuticals-inc-announces-aegr-r904473.htm | archive-date=2012-02-29 }}</ref> |
|
}}</ref> |
|
|
It has been tested in several Phase II ] as single treatment and in combinations with ], ] and ].<ref>{{cite journal|last=Samaha|first=Frederick F|coauthors=James McKenney, LeAnne T Bloedon, William J Sasiela, Daniel J Rader|date=2008|title=Impact of the MTP-Inhibitor, AEGR-733, as Monotherapy and in Combination with Ezetimibe on Lipid Subfractions as Measured by NMR Spectroscopy|journal=Circulation|volume=118|pages=469|pmid=18663098|issue=5|doi=10.1161/CIRCULATIONAHA.108.792689}}</ref><ref></ref> |
|
|
|
|
|
|
|
The US Food and Drug Administration (FDA) approved lomitapide in December 2012, as an ] to reduce ], total ], ], and ] in people with ] (HoFH).<ref>{{cite web | url = https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm333285.htm | archive-url = https://web.archive.org/web/20130128180135/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm333285.htm | archive-date = 28 January 2013 | title = FDA approves new orphan drug for rare cholesterol disorder | publisher = U.S. Food and Drug Administration }}</ref> |
|
A Phase III trial has started in December 2007 and will be running until August 2011.<ref>{{ClinicalTrialsGov|NCT00730236|A Safety and Efficacy Study of AEGR-733 to Treat Homozygous Familial Hypercholesterolemia (FH)}}</ref> |
|
|
|
|
|
|
In July 2013, the European Commission approved lomitapide as an adjunct to a low-fat diet and other lipid-lowering medicinal products with or without low density lipoprotein (LDL) ] in adults with HoFH.<ref name="Lojuxta EPAR">{{cite web | title=Lojuxta EPAR | website=] (EMA) | url=https://www.ema.europa.eu/en/medicines/human/EPAR/lojuxta | access-date=27 January 2021}}</ref> |
|
|
|
|
|
==Mechanism of action== |
|
==Mechanism of action== |
|
Lomitapide inhibits the ] (MTP or MTTP) which is necessary for ] (VLDL) assembly and secretion in the liver.<ref name="Spreitzer" /><ref name="pmid17215532">{{pmid|17215532}}</ref> |
|
Lomitapide inhibits the ] (MTP or MTTP) which is necessary for ] (VLDL) assembly and secretion in the liver.<ref name="Spreitzer" /><ref name="pmid17215532">{{cite journal | vauthors = Cuchel M, Bloedon LT, Szapary PO, Kolansky DM, Wolfe ML, Sarkis A, Millar JS, Ikewaki K, Siegelman ES, Gregg RE, Rader DJ | display-authors = 6 | title = Inhibition of microsomal triglyceride transfer protein in familial hypercholesterolemia | journal = The New England Journal of Medicine | volume = 356 | issue = 2 | pages = 148–56 | date = January 2007 | pmid = 17215532 | doi = 10.1056/NEJMoa061189 | doi-access = free }}</ref> |
|
|
|
|
|
In December 2012, drug manufacturer Aegerion announced they had been approved by the FDA to as "an adjunct to a low-fat diet and other lipid-lowering treatments...in patients with homozygous familial hypercholesterolemia (HoFH)."<ref>{{cite web|title=FDA Approves Juxtapid for Homozygous Familial Hypercholesteolemia|url=http://www.dailyrx.com/juxtapid-reduces-cholesterol-patients-homozygous-familial-hypercholesterolemia|date=26 December 2012|access-date=1 January 2013|archive-url=https://web.archive.org/web/20121229140605/http://www.dailyrx.com/juxtapid-reduces-cholesterol-patients-homozygous-familial-hypercholesterolemia|archive-date=29 December 2012|url-status=dead}}</ref><ref>{{cite press release | url = http://ir.aegerion.com/releasedetail.cfm?ReleaseID=728650 | title = FDA Approves Aegerion Pharmaceuticals' Juxtapid (lomitapide) Capsules for Homozygous Familial Hypercholesterolemia (HoFH) | publisher = Aegerion Pharmaceuticals | date = 24 December 2012 | access-date = 1 January 2013 | archive-url = https://web.archive.org/web/20160922115515/http://ir.aegerion.com/releasedetail.cfm?releaseid=728650 | archive-date = 22 September 2016 | url-status = dead }}</ref> |
|
|
|
|
|
==Side effects== |
|
==Side effects== |
|
In a Phase II study, lomitapide lead to elevated ] levels and fat accumulation in the liver.<ref name="pmid17215532" /> |
|
In a ], lomitapide led to elevated ] levels and fat accumulation in the liver.<ref name="pmid17215532" /> |
|
|
|
|
|
==References== |
|
== References == |
|
{{Reflist}} |
|
{{Reflist}} |
|
|
|
|
|
|
== External links == |
|
] |
|
|
|
* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/lomitapide | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Lomitapide }} |
|
] |
|
|
|
|
|
|
{{Lipid modifying agents}} |
|
|
{{Portal bar | Medicine}} |
|
|
|
|
] |
|
] |
|
] |
|
] |
|
] |
|
] |
|
] |
|
] |
|
] |
|
] |
|
|
] |
|
|
|
|
|
] |
|
|
|
|
|
] |
|
{{cardiovascular-drug-stub}} |
|
|
|
] |
|
|
|
|
] |
|