Details of the Drug

General Information of Drug (ID: DMRJSP8)

Drug Name
Orlistat
Synonyms
orlistat; 96829-58-2; Tetrahydrolipstatin; Xenical; Alli; Orlipastat; (-)-Tetrahydrolipstatin; Orlipastatum; Orlipastatum [INN-Latin]; THLP; Ro-18-0647; UNII-95M8R751W8; C29H53NO5; Ro 18-0647/002; N-Formyl-L-leucine (1S)-1-[[(2S,3S)-3-hexyl-4-oxo-2-oxetanyl]methyl]dodecyl ester; (2S)-1-[(2S,3S)-3-hexyl-4-oxooxetan-2-yl]tridecan-2-yl (2S)-2-formamido-4-methylpentanoate; Orlistat (Alli, Xenical); MLS002207022; [(2S)-1-[(2S,3S)-3-hexyl-4-oxooxetan-2-yl]tridecan-2-yl] (2S)-2-formamido-4-methylpentanoate; CHEMBL175247; Alli; GlaxoSmithKline brand of orlistat; Roche brand of orlistat; Alli (TN); Hoffmann-La Roche brand of orlistat; KS-1183; Orlistat [USAN:INN]; R-212; Xenical (TN); Orlistat (USAN/INN); Ro 18-0647/008; Alli, Xenical, Tetrahydrolipstatin, Orlistat; N-Formyl-L-leucine, ester with (3S,4S)-3-hexyl-4-((2S)-2-hydroxytridecyl)-2-oxetanone; L-Leucine, N-formyl-, (1S)-1-(((2S,3S)-3-hexyl-4-oxo-2-oxetanyl)methyl)dodecyl ester; L-Leucine,N-formyl-, (1S)-1-(((2S,3S)-3-hexyl-4-oxo-2-oxetanyl)methyl)dodecyl ester; 1-((3-hexyl-4-oxo-2-oxetanyl)methyl)dodecyl-2-formamido-4-methylvalerate; TETRAHYDROLIPSTATIN
Indication
Disease Entry ICD 11 Status REF
Obesity 5B81 Approved [1]
Therapeutic Class
Antiobesity Agents
Affected Organisms
Humans and other mammalsMouseRat
ATC Code
A08AB01: Orlistat
A08AB: Peripherally acting antiobesity products
A08A: ANTIOBESITY PREPARATIONS, EXCL. DIET PRODUCTS
A08: ANTIOBESITY PREPARATIONS, EXCL. DIET PRODUCTS
A: ALIMENTARY TRACT AND METABOLISM
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 2 Molecular Weight (mw) 495.7
Logarithm of the Partition Coefficient (xlogp) 10
Rotatable Bond Count (rotbonds) 23
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 5
ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 4: low solubility and low permeability [2]
Elimination
After single oral dose of radiolabled orlistat in both normal weight and obese volunteers fecal excretion of the unabsorbed drug was found to be the major route of elimination with <2% urinary excretion [3]
Half-life
The concentration or amount of drug in body reduced by one-half in 1 - 2 hours [4]
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 9.221 micromolar/kg/day [5]
Chemical Identifiers
Formula
C29H53NO5
IUPAC Name
[(2S)-1-[(2S,3S)-3-hexyl-4-oxooxetan-2-yl]tridecan-2-yl] (2S)-2-formamido-4-methylpentanoate
Canonical SMILES
CCCCCCCCCCC[C@@H](C[C@H]1[C@@H](C(=O)O1)CCCCCC)OC(=O)[C@H](CC(C)C)NC=O
InChI
InChI=1S/C29H53NO5/c1-5-7-9-11-12-13-14-15-16-18-24(34-29(33)26(30-22-31)20-23(3)4)21-27-25(28(32)35-27)19-17-10-8-6-2/h22-27H,5-21H2,1-4H3,(H,30,31)/t24-,25-,26-,27-/m0/s1
InChIKey
AHLBNYSZXLDEJQ-FWEHEUNISA-N
Cross-matching ID
PubChem CID
3034010
ChEBI ID
CHEMBL175247
CAS Number
96829-58-2
UNII
95M8R751W8
DrugBank ID
DB01083
TTD ID
D0T9TJ
ACDINA ID
D00491
Drug-Molecule Activity Atlas (DMA)NEW Click to Jump to the Detailed DMA Information of This Drug
Drug Pharmacogenomic Perturbation (DPP)NEW Click to Jump to the Detailed DPP Information of This Drug
Drug ADMET Endpoint Profile (DAE)NEW Click to Jump to the Detailed DAE Information of This Drug
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Cannabinoid receptor 1 (CB1) TT6OEDT CNR1_HUMAN Inhibitor [6]
Pancreatic triacylglycerol lipase (PNLIP) TTXMY0J LIPP_HUMAN Modulator [7]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Acetyl-CoA carboxylase 1 (ACACA) OT5CQPZY ACACA_HUMAN Gene/Protein Processing [8]
Acyl-coenzyme A thioesterase 8 (ACOT8) OTHY684G ACOT8_HUMAN Gene/Protein Processing [9]
Carnitine O-palmitoyltransferase 1, liver isoform (CPT1A) OTI862QH CPT1A_HUMAN Gene/Protein Processing [9]
Carnitine O-palmitoyltransferase 2, mitochondrial (CPT2) OTIN6G20 CPT2_HUMAN Gene/Protein Processing [9]
Cyclic AMP-dependent transcription factor ATF-4 (ATF4) OTRFV19J ATF4_HUMAN Gene/Protein Processing [10]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Gene/Protein Processing [9]
Cyclin-dependent kinase inhibitor 1B (CDKN1B) OTNY5LLZ CDN1B_HUMAN Gene/Protein Processing [11]
DNA damage-inducible transcript 3 protein (DDIT3) OTI8YKKE DDIT3_HUMAN Gene/Protein Processing [10]
DNA damage-inducible transcript 4 protein (DDIT4) OTHY8SY4 DDIT4_HUMAN Gene/Protein Processing [12]
ER lumen protein-retaining receptor 3 (KDELR3) OTW8C1V0 ERD23_HUMAN Gene/Protein Processing [12]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Obesity
ICD Disease Classification 5B81
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Cannabinoid receptor 1 (CB1) DTT CNR1 5.59E-02 -0.22 -0.45
Cannabinoid receptor 1 (CB1) DTT CNR1 7.68E-01 -0.06 -0.46
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Orlistat (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Remdesivir DMBFZ6L Moderate Increased risk of hepatotoxicity by the combination of Orlistat and Remdesivir. 1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019] [13]
Bedaquiline DM3906J Moderate Increased risk of hepatotoxicity by the combination of Orlistat and Bedaquiline. Antimicrobial drug resistance [MG50-MG52] [14]
Pexidartinib DMS2J0Z Major Increased risk of hepatotoxicity by the combination of Orlistat and Pexidartinib. Bone/articular cartilage neoplasm [2F7B] [15]
Doxercalciferol DM6FG1P Minor Decreased absorption of Orlistat caused by Doxercalciferol. Chronic kidney disease [GB61] [16]
Anisindione DM2C48U Moderate Altered absorption of Orlistat caused by Anisindione. Coagulation defect [3B10] [17]
Ospemifene DMC4GEI Moderate Altered absorption of Orlistat caused by Ospemifene. Dyspareunia [GA12] [18]
Cannabidiol DM0659E Moderate Increased risk of hepatotoxicity by the combination of Orlistat and Cannabidiol. Epileptic encephalopathy [8A62] [18]
Boceprevir DMBSHMF Moderate Altered absorption of Orlistat caused by Boceprevir. Hepatitis virus infection [1E50-1E51] [19]
Telaprevir DMMRV29 Moderate Altered absorption of Orlistat caused by Telaprevir. Hepatitis virus infection [1E50-1E51] [19]
Telbivudine DMSWUGE Moderate Altered absorption of Orlistat caused by Telbivudine. Hepatitis virus infection [1E50-1E51] [19]
Brentuximab vedotin DMWLC57 Moderate Increased risk of hepatotoxicity by the combination of Orlistat and Brentuximab vedotin. Hodgkin lymphoma [2B30] [20]
Fosamprenavir DM4W9B3 Moderate Altered absorption of Orlistat caused by Fosamprenavir. Human immunodeficiency virus disease [1C60-1C62] [19]
Dolutegravir DMCZGRE Moderate Altered absorption of Orlistat caused by Dolutegravir. Human immunodeficiency virus disease [1C60-1C62] [19]
Saquinavir DMG814N Moderate Altered absorption of Orlistat caused by Saquinavir. Human immunodeficiency virus disease [1C60-1C62] [19]
Elvitegravir DMG9B1U Moderate Altered absorption of Orlistat caused by Elvitegravir. Human immunodeficiency virus disease [1C60-1C62] [19]
Rilpivirine DMJ0QOW Moderate Altered absorption of Orlistat caused by Rilpivirine. Human immunodeficiency virus disease [1C60-1C62] [19]
Darunavir DMN3GCH Moderate Altered absorption of Orlistat caused by Darunavir. Human immunodeficiency virus disease [1C60-1C62] [19]
Raltegravir DMYURI6 Moderate Altered absorption of Orlistat caused by Raltegravir. Human immunodeficiency virus disease [1C60-1C62] [19]
Mipomersen DMGSRN1 Major Increased risk of hepatotoxicity by the combination of Orlistat and Mipomersen. Hyper-lipoproteinaemia [5C80] [21]
Teriflunomide DMQ2FKJ Major Increased risk of hepatotoxicity by the combination of Orlistat and Teriflunomide. Hyper-lipoproteinaemia [5C80] [22]
BMS-201038 DMQTAGO Major Increased risk of hepatotoxicity by the combination of Orlistat and BMS-201038. Hyper-lipoproteinaemia [5C80] [23]
Glycerol phenylbutyrate DMDGRQO Moderate Altered absorption of Orlistat caused by Glycerol phenylbutyrate. Liver disease [DB90-DB9Z] [18]
Calaspargase pegol DMQZBXI Moderate Increased risk of hepatotoxicity by the combination of Orlistat and Calaspargase pegol. Malignant haematopoietic neoplasm [2B33] [24]
Idelalisib DM602WT Moderate Increased risk of hepatotoxicity by the combination of Orlistat and Idelalisib. Mature B-cell leukaemia [2A82] [25]
Leflunomide DMR8ONJ Major Increased risk of hepatotoxicity by the combination of Orlistat and Leflunomide. Rheumatoid arthritis [FA20] [22]
Trabectedin DMG3Y89 Moderate Increased risk of hepatotoxicity by the combination of Orlistat and Trabectedin. Solid tumour/cancer [2A00-2F9Z] [18]
Amiodarone DMUTEX3 Moderate Decreased absorption of Orlistat caused by Amiodarone. Ventricular tachyarrhythmia [BC71] [16]
⏷ Show the Full List of 27 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG
DIG Name DIG ID PubChem CID Functional Classification
FD&C blue no. 1 E00263 19700 Colorant
FD&C blue no. 2 E00446 2723854 Colorant
Isopropyl alcohol E00070 3776 Antimicrobial preservative; Solvent
Sodium lauryl sulfate E00464 3423265 Emulsifying agent; Modified-release agent; Penetration agent; Solubilizing agent; Surfactant; lubricant
Ammonia E00007 222 Alkalizing agent
Butyl alcohol E00011 263 Flavoring agent; Solvent
Ferrosoferric oxide E00231 14789 Colorant
Ferrous oxide E00241 14945 Colorant
Potassium hydroxide E00233 14797 Alkalizing agent
Propylene glycol E00040 1030 Antimicrobial preservative; Humectant; Plasticizing agent; Solvent
Talc E00520 16211421 Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide E00322 26042 Coating agent; Colorant; Opacifying agent
⏷ Show the Full List of 12 Pharmaceutical Excipients of This Drug
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Orlistat 120 mg capsule 120 mg Oral Capsule Oral
Orlistat 60 mg capsule 60 mg Oral Capsule Oral
Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
2 BDDCS applied to over 900 drugs
3 FDA Approved Drug Products: Xenical (orlistat) capsules
4 Metabolic profiles of minimally absorbed orlistat in obese/overweight volunteers. J Clin Pharmacol. 1996 Nov;36(11):1006-11. doi: 10.1177/009127009603601104.
5 Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
6 Tetrahydrolipstatin analogues as modulators of endocannabinoid 2-arachidonoylglycerol metabolism. J Med Chem. 2008 Nov 13;51(21):6970-9.
7 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
8 Diosgenin and 4-Hydroxyisoleucine from Fenugreek Are Regulators of Genes Involved in Lipid Metabolism in The Human Colorectal Cancer Cell Line SW480. Cell J. 2021 Jan;22(4):514-522. doi: 10.22074/cellj.2021.6751. Epub 2020 Apr 22.
9 Orlistat Displays Antitumor Activity and Enhances the Efficacy of Paclitaxel in Human Hepatoma Hep3B Cells. Chem Res Toxicol. 2019 Feb 18;32(2):255-264. doi: 10.1021/acs.chemrestox.8b00269. Epub 2019 Jan 22.
10 Inhibition of fatty acid synthase induces endoplasmic reticulum stress in tumor cells. Cancer Res. 2007 Feb 1;67(3):1262-9. doi: 10.1158/0008-5472.CAN-06-1794.
11 A fatty acid synthase blockade induces tumor cell-cycle arrest by down-regulating Skp2. J Biol Chem. 2004 Jul 16;279(29):30540-5. doi: 10.1074/jbc.M405061200. Epub 2004 May 11.
12 Inhibition of fatty-acid synthase induces caspase-8-mediated tumor cell apoptosis by up-regulating DDIT4. J Biol Chem. 2008 Nov 14;283(46):31378-84. doi: 10.1074/jbc.M803384200. Epub 2008 Sep 16.
13 Cerner Multum, Inc. "Australian Product Information.".
14 Product Information. Sirturo (bedaquiline). Janssen Pharmaceuticals, Titusville, NJ.
15 Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
16 Product Information. Xenical (orlistat). Roche Laboratories, Nutley, NJ.
17 MacWalter RS, Fraser HW, Armstrong KM "Orlistat enhances warfarin effect." Ann Pharmacother 37 (2003): 510-2. [PMID: 12659605]
18 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
19 MHRA. Medicines and Healthcare Products Regulatory Agency "Orlistat: theoretical interaction with antiretroviral HIV medicines.".
20 Product Information. Adcetris (brentuximab vedotin). Seattle Genetics Inc, Bothell, WA.
21 Product Information. Kynamro (mipomersen). Genzyme Corporation, Cambridge, MA.
22 Canadian Pharmacists Association.
23 Product Information. Juxtapid (lomitapide). Aegerion Pharmaceuticals Inc, Cambridge, MA.
24 Al-Nawakil C, Willems L, Mauprivez C, et.al "Successful treatment of l-asparaginase-induced severe acute hepatotoxicity using mitochondrial cofactors." Leuk Lymphoma 55 (2014): 1670-4. [PMID: 24090500]
25 Product Information. Zydelig (idelalisib). Gilead Sciences, Foster City, CA.