Details of the Drug

General Information of Drug (ID: DM1NOEK)

• Drug Name: Metreleptin

Indication

Disease Entry	ICD 11	Status	REF
Acquired generalized lipodystrophy	N.A.	Approved	[1]
Congenital generalized lipodystrophy	N.A.	Approved	[1]
Diabetic complication	5A2Y	Approved	[2]
Acquired partial lipodystrophy	N.A.	Investigative	[1]

• Affected Organisms: Humans and other mammals
• ATC Code:
  A16AA07: Metreleptin
  A16AA: Amino acids and derivatives
  A16A: OTHER ALIMENTARY TRACT AND METABOLISM PRODUCTS
  A16: OTHER ALIMENTARY TRACT AND METABOLISM PRODUCTS
  A: ALIMENTARY TRACT AND METABOLISM
• Sequence:
  MVPIQKVQDDTKTLIKTIVTRINDISHTQSVSSKQKVTGLDFIPGLHPILTLSKMDQTLA
  VYQQILTSMPSRNVIQISNDLENLRDLLHVLAFSKSCHLPWASGLETLDSLGGVLEASGY
  STEVVALSRLQGSLQDMLWQLDLSPGC
• ADMET Property:
  Half-life: The concentration or amount of drug in body reduced by one-half in 3.8 - 4.7 hours [3]
  Metabolism: The drug is metabolized via renal []
  Vd: The volume of distribution (Vd) of drug is 0.37 L/kg []
• Cross-matching ID:
  UNII: TL60C27RLH
  DrugBank ID: DB09046
  TTD ID: D0Z9EO
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Leptin receptor (LEPR)	TT0HD6V	LEPR_HUMAN	Modulator	[4]

Molecular Expression Atlas of This Drug

• The Studied Disease: Acquired generalized lipodystrophy

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Leptin receptor (LEPR)	DTT	LEPR	5.82E-02	0.05	0.15

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Metreleptin (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Oliceridine	DM6MDCF	Moderate	Increased metabolism of Metreleptin caused by Oliceridine mediated induction of CYP450 enzyme.	Acute pain [MG31]	[5]
Ivabradine	DM0L594	Moderate	Increased metabolism of Metreleptin caused by Ivabradine mediated induction of CYP450 enzyme.	Angina pectoris [BA40]	[6]
LY2835219	DM93VBZ	Moderate	Increased metabolism of Metreleptin caused by LY2835219 mediated induction of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[7]
Tucatinib	DMBESUA	Moderate	Increased metabolism of Metreleptin caused by Tucatinib mediated induction of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[8]
Palbociclib	DMD7L94	Moderate	Increased metabolism of Metreleptin caused by Palbociclib mediated induction of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[9]
Alpelisib	DMEXMYK	Moderate	Increased metabolism of Metreleptin caused by Alpelisib mediated induction of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[10]
PF-04449913	DMSB068	Moderate	Increased metabolism of Metreleptin caused by PF-04449913 mediated induction of CYP450 enzyme.	Chronic myelomonocytic leukaemia [2A40]	[11]
Levonorgestrel	DM1DP7T	Moderate	Decreased metabolism of Metreleptin caused by Levonorgestrel mediated inhibition of CYP450 enzyme.	Contraceptive management [QA21]	[12]
Oestradiol valerate and dienogest	DMZK0FQ	Moderate	Decreased metabolism of Metreleptin caused by Oestradiol valerate and dienogest mediated inhibition of CYP450 enzyme.	Endometriosis [GA10]	[13]
Tazemetostat	DMWP1BH	Moderate	Increased metabolism of Metreleptin caused by Tazemetostat mediated induction of CYP450 enzyme.	Follicular lymphoma [2A80]	[14]
Ripretinib	DM958QB	Moderate	Increased metabolism of Metreleptin caused by Ripretinib mediated induction of CYP450 enzyme.	Gastrointestinal stromal tumour [2B5B]	[9]
Avapritinib	DMK2GZX	Moderate	Increased metabolism of Metreleptin caused by Avapritinib mediated induction of CYP450 enzyme.	Gastrointestinal stromal tumour [2B5B]	[6]
MK-1439	DM215WE	Moderate	Increased metabolism of Metreleptin caused by MK-1439 mediated induction of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[15]
Fostemsavir	DM50ILT	Minor	Increased metabolism of Metreleptin caused by Fostemsavir mediated induction of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[16]
Naloxegol	DML0B41	Moderate	Increased metabolism of Metreleptin caused by Naloxegol mediated induction of CYP450 enzyme.	Large intestine motility disorder [DB32]	[17]
Pemigatinib	DM819JF	Moderate	Increased metabolism of Metreleptin caused by Pemigatinib mediated induction of CYP450 enzyme.	Liver cancer [2C12]	[6]
Brigatinib	DM7W94S	Moderate	Increased metabolism of Metreleptin caused by Brigatinib mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[9]
Ceritinib	DMB920Z	Moderate	Increased metabolism of Metreleptin caused by Ceritinib mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[18]
Lurbinectedin	DMEFRTZ	Moderate	Increased metabolism of Metreleptin caused by Lurbinectedin mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[19]
Osimertinib	DMRJLAT	Moderate	Increased metabolism of Metreleptin caused by Osimertinib mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[20]
Capmatinib	DMYCXKL	Moderate	Increased metabolism of Metreleptin caused by Capmatinib mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[21]
Selpercatinib	DMZR15V	Moderate	Increased metabolism of Metreleptin caused by Selpercatinib mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[6]
Idelalisib	DM602WT	Moderate	Increased metabolism of Metreleptin caused by Idelalisib mediated induction of CYP450 enzyme.	Mature B-cell leukaemia [2A82]	[22]
GDC-0199	DMH0QKA	Moderate	Increased metabolism of Metreleptin caused by GDC-0199 mediated induction of CYP450 enzyme.	Mature B-cell leukaemia [2A82]	[23]
IPI-145	DMWA24P	Moderate	Increased metabolism of Metreleptin caused by IPI-145 mediated induction of CYP450 enzyme.	Mature B-cell leukaemia [2A82]	[24]
Acalabrutinib	DM7GCVW	Moderate	Increased metabolism of Metreleptin caused by Acalabrutinib mediated induction of CYP450 enzyme.	Mature B-cell lymphoma [2A85]	[25]
Selumetinib	DMC7W6R	Moderate	Increased metabolism of Metreleptin caused by Selumetinib mediated induction of CYP450 enzyme.	Melanoma [2C30]	[26]
LGX818	DMNQXV8	Moderate	Increased metabolism of Metreleptin caused by LGX818 mediated induction of CYP450 enzyme.	Melanoma [2C30]	[27]
Ubrogepant	DM749I3	Moderate	Increased metabolism of Metreleptin caused by Ubrogepant mediated induction of CYP450 enzyme.	Migraine [8A80]	[28]
Rolapitant	DM8XP26	Moderate	Increased metabolism of Metreleptin caused by Rolapitant mediated induction of CYP450 enzyme.	Nausea/vomiting [MD90]	[29]
Entrectinib	DMMPTLH	Moderate	Increased metabolism of Metreleptin caused by Entrectinib mediated induction of CYP450 enzyme.	Non-small cell lung cancer [2C25]	[30]
Olaparib	DM8QB1D	Moderate	Increased metabolism of Metreleptin caused by Olaparib mediated induction of CYP450 enzyme.	Ovarian cancer [2C73]	[9]
Macimorelin	DMQYJIR	Moderate	Increased metabolism of Metreleptin caused by Macimorelin mediated induction of CYP450 enzyme.	Pituitary gland disorder [5A60-5A61]	[31]
LDE225	DMM9F25	Moderate	Increased metabolism of Metreleptin caused by LDE225 mediated induction of CYP450 enzyme.	Skin cancer [2C30-2C37]	[32]
LEE011	DMMX75K	Moderate	Increased metabolism of Metreleptin caused by LEE011 mediated induction of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[9]
Fostamatinib	DM6AUHV	Moderate	Increased metabolism of Metreleptin caused by Fostamatinib mediated induction of CYP450 enzyme.	Thrombocytopenia [3B64]	[33]

References

• [1] Lipodystrophy Syndromes. Endocrinol Metab Clin North Am. 2016 Dec;45(4):783-797.
• [2] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7333).
• [3] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [4] 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
• [5] Altice FL, Friedland GH, Cooney EL "Nevirapine induced opiate withdrawal among injection drug users with HIV infection receiving methadone." AIDS 13 (1999): 957-62. [PMID: 10371177]
• [6] Cerner Multum, Inc. "UK Summary of Product Characteristics.".
• [7] Product Information. Verzenio (abemaciclib). Lilly, Eli and Company, Indianapolis, IN.
• [8] Product Information. Tukysa (tucatinib). Seattle Genetics Inc, Bothell, WA.
• [9] Cerner Multum, Inc. "Australian Product Information.".
• [10] Product Information. Piqray (alpelisib). Novartis Pharmaceuticals, East Hanover, NJ.
• [11] Product Information. Daurismo (glasdegib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
• [12] Product Information. Myalept (metreleptin). Bristol-Myers Squibb, Princeton, NJ.
• [13] Bailey DG, Arnold JMO, Spence JD "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet 26 (1994): 91-8. [PMID: 8162660]
• [14] Product Information. Tazverik (tazemetostat). Epizyme, Inc, Cambridge, MA.
• [15] Product Information. Pifeltro (doravirine). Merck & Company Inc, Whitehouse Station, NJ.
• [16] Product Information. Rukobia (fostemsavir). ViiV Healthcare, Research Triangle Park, NC.
• [17] Product Information. Movantik (naloxegol). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
• [18] Product Information. Zykadia (ceritinib). Novartis Pharmaceuticals, East Hanover, NJ.
• [19] Product Information. Zepzelca (lurbinectedin). Jazz Pharmaceuticals, Palo Alto, CA.
• [20] Product Information. Tagrisso (osimertinib). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
• [21] Product Information. Tabrecta (capmatinib). Novartis Pharmaceuticals, East Hanover, NJ.
• [22] Product Information. Zydelig (idelalisib). Gilead Sciences, Foster City, CA.
• [23] Product Information. Venclexta (venetoclax). AbbVie US LLC, North Chicago, IL.
• [24] Product Information. Copiktra (duvelisib). Verastem, Inc., Needham, MA.
• [25] Product Information. Calquence (acalabrutinib). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
• [26] Product Information. Koselugo (selumetinib). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
• [27] Product Information. Braftovi (encorafenib). Array BioPharma Inc., Boulder, CO.
• [28] Product Information. Ubrelvy (ubrogepant). Allergan Inc, Irvine, CA.
• [29] Product Information. Varubi (rolapitant). Tesaro Inc., Waltham, MA.
• [30] Product Information. Rozlytrek (entrectinib). Genentech, South San Francisco, CA.
• [31] Product Information. Macrilen (macimorelin). Aeterna Zentaris, Charleston, SC.
• [32] Product Information. Odomzo (sonidegib). Novartis Pharmaceuticals, East Hanover, NJ.
• [33] Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.