ORLISTAT

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C29H53NO5
Molecular Weight	495.7348
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCCCCCCCCCC[C@@H](C[C@@H]1OC(=O)[C@H]1CCCCCC)OC(=O)[C@H](CC(C)C)NC=O

InChI

InChIKey=AHLBNYSZXLDEJQ-FWEHEUNISA-N

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

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/11249520
Curator's Comment: Description was created based on several sources, including http://www.fda.gov/downloads/UCM205349.pdf https://www.ncbi.nlm.nih.gov/pubmed/9225172 https://www.ncbi.nlm.nih.gov/pubmed/16956313

Orlistat or tetrahydrolipstatin (Xenical, Hoffmann-La Roche) is a saturated derivative of lipstatin originally isolated from Streptomyces toxytricini. Orlistat (Xenical, Hoffmann-La Roche) is a powerful inhibitor of gastrointestinal lipase and as such, reduces fat absorption. Orlistat acts by binding covalently to the serine residue of the active site of gastric and pancreatic lipases. When administered with fat-containing foods, orlistat partially inhibits hydrolysis of triglycerides, thus reducing the subsequent absorption of monoaclglycerides and free fatty acids. Unlike other weight-reducing drugs it is minimally absorbed and has no effects in the CNS. Xenical is indicated for obesity management including weight loss and weight maintenance when used in conjunction witha reduced-calorie diet. XENICAL is also indicated to reduce the risk for weight regain after prior weight loss. XENICAL is indicated for obese patients with an initial body mass index (BMI) ≥ 30 kg/m2 or ≥ 27 kg/m2 in the presence of other risk factors (eg, hypertension, diabetes, dyslipidemia). In addition to its well established efficacy in achieving modest weight loss, orlistat has been shown to improve glycaemic parameters in obese adults with type 2 diabetes mellitus as well as some features of the metabolic syndrome.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Pancreatic lipase 5 Target ID: CHEMBL1812 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12381337 \| https://www.ncbi.nlm.nih.gov/pubmed/11408251	Inhibitor 8504
Fatty acid synthase 6 Target ID: CHEMBL4158 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15026345	Inhibitor 8504	100.0 nM [Ki]
Gastric lipase 1 Target ID: CHEMBL1796 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12381337 \| https://www.ncbi.nlm.nih.gov/pubmed/11408251	Inhibitor 8504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Obesity 206 Sources: http://www.fda.gov/downloads/UCM205349.pdf	Primary		Approved 8583	XENICAL Approved Use XENICAL orlistat capsule is indicated for obesity management including weight loss and weight maintenance when used in conjunction with a reduced-calorie diet. XENICAL is also indicated to reduce the risk for weight regain after prior weight loss. XENICAL is indicated for obese patients with an initial body mass index (BMI) ≥30 kg/m2 or ≥27 kg/m2 in the presence of other risk factors (eg, hypertension, diabetes, dyslipidemia). Launch Date 1999

C_max

Value	Dose	Co-administered	Analyte	Population
150 ng × eq/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8973989	360 mg single, oral dose: 360 mg route of administration: Oral experiment type: SINGLE co-administered:		ORLISTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED

AUC

Value	Dose	Co-administered	Analyte	Population
907 ng × eq × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8973989	360 mg single, oral dose: 360 mg route of administration: Oral experiment type: SINGLE co-administered:		ORLISTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.5 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020766s029lbl.pdf			ORLISTAT plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
1% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020766s029lbl.pdf			ORLISTAT plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:94686	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:94686
ChemicalBook	CB2431985	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB2431985
eMolecules	593023	https://www.emolecules.com/cgi-bin/more?vid=593023
MolPort	MolPort-005-938-035	https://www.molport.com/shop/molecule-link/MolPort-005-938-035
Selleck Chemicals	Orlistat(Alli)	http://www.selleckchem.com/products/Orlistat(Alli).html
ZINC	ZINC000008214635	http://zinc15.docking.org/substances/ZINC000008214635

PubMed

Title	Date	PubMed
Orlistat.	2000 Mar-Apr	11728255
Orlistat: in the prevention and treatment of type 2 diabetes mellitus.	2001	11735640
Primary care diabetes. What options are there?	2001 Dec	11838389
Bulimia nervosa and misuse of orlistat: two case reports.	2001 Dec	11746308
American College of Sports Medicine position stand. Appropriate intervention strategies for weight loss and prevention of weight regain for adults.	2001 Dec	11740312
["Xenical doesn't function"--theory and reality].	2001 Dec 12	11789108
[Changes in lipid profile and paraoxonase activity in obese patients as a result of orlistat treatment].	2001 Dec 16	11820148
Online prescriptions of pharmaceuticals: where is the evidence for harm or for benefit? A call for papers--and for reflection.	2001 Jan-Mar	11720943
Current methods used for defining, measuring, and treating obesity.	2001 Nov	11769877
The effects of orlistat on weight and on serum lipids in obese patients with hypercholesterolemia: a randomized, double-blind, placebo-controlled, multicentre study.	2001 Nov	11753595
[Inhibitors of absorption as anti-obesity drugs].	2001 Nov	11729638
Interaction between orlistat and antihypertensive drugs.	2001 Nov	11724110
Lipoprotein lipase mediates an increase in selective uptake of HDL-associated cholesteryl esters by cells in culture independent of scavenger receptor BI.	2001 Nov	11714843
[Drugs for obesity. Why are obese patients diferent?].	2001 Nov 3	11707221
[Application for exemption concerning Xenical was refused without explanation].	2001 Nov 7	11816911
Drug treatment of obesity.	2001 Oct	11725727
[Obesity and cardiovascular risk].	2001 Sep	11787368
The advances on the knowledge base of obesity and future therapeutic directions.	2001 Sep	11706508
[Weight reduction. Antiobesity drug treatment in type-2 diabetics].	2002	12071127
[Six-month xenical (orlistat) therapy of patients with stable angina pectoris concomitant with obesity and hyperlipidemia].	2002	11878059
[Orlistat. A treatment of limited value for obese persons].	2002 Apr	12046132
Roche turns to DM to boost patient compliance with its weight loss drug.	2002 Apr	11995433
Results of obesity treatment.	2002 Apr	11994682
The cerebrospinal fluid/serum leptin ratio during pharmacological therapy for obesity.	2002 Apr	11932292
Orlistat: its current status as an anti-obesity drug.	2002 Apr 12	12007529
Biosynthetic precursors of the lipase inhibitor lipstatin.	2002 Apr 5	11925237
Effects of lipoprotein lipase on uptake and transcytosis of low density lipoprotein (LDL) and LDL-associated alpha-tocopherol in a porcine in vitro blood-brain barrier model.	2002 Aug 9	12032155
Orlistat: a second look. At best, a minor adjunct to dietary measures.	2002 Feb	11985367
Reduction in blood cyclosporine concentration by orlistat in two renal transplant patients.	2002 Feb	11959223
Impact of orlistat therapy on weight reduction in morbidly obese patients after implantation of the Swedish adjustable gastric band.	2002 Feb	11868286
A health economic model to assess the long-term effects and cost-effectiveness of orlistat in obese type 2 diabetic patients.	2002 Feb	11815500
The effect of orlistat on plasma levels of psychotropic drugs in patients with long-term psychopharmacotherapy.	2002 Feb	11799345
Are soft tissue composition of bone and non-bone pixels in spinal bone mineral measurements by DXA similar? Impact of weight loss.	2002 Jan	12003104
Minor long-term changes in weight have beneficial effects on insulin sensitivity and beta-cell function in obese subjects.	2002 Jan	11890163
Evaluation of the safety and efficacy of sibutramine, orlistat and metformin in the treatment of obesity.	2002 Jan	11874442
Obesity.	2002 Jan	11788535
Usefulness of Orlistat in the treatment of severe hypertriglyceridemia.	2002 Jan 15	11792350
[Treatment in the community health centers in accordance with recommendations of the Medical Products Agency. Unsatisfactory weight reduction with orlistat].	2002 Jan 31	11881245
[Are drugs necessary in the treatment of obesity?].	2002 Jan-Feb	12037933
Constipation, polyuria, polydipsia, and edema associated with orlistat.	2002 Jul-Aug	12086548
Combining behavioral and pharmacological treatments for obesity.	2002 Jun	12055334
Clinical efficacy of orlistat therapy in overweight and obese patients with insulin-treated type 2 diabetes: A 1-year randomized controlled trial.	2002 Jun	12032111
Additive gastrointestinal effects with concomitant use of olestra and orlistat.	2002 Jun	12022901
Demand, appropriateness and prescribing of 'lifestyle drugs': a consultation survey in general practice.	2002 Jun	11978712
Can drugs help you lose weight?	2002 Mar	11916631
Orlistat misuse in bulimia nervosa.	2002 Mar	11870021
[Anti-obesity drugs: sibutramine and orlistat].	2002 Mar 30	11943108
Serine and threonine beta-lactones: a new class of hepatitis A virus 3C cysteine proteinase inhibitors.	2002 Mar 8	11871884
Obesity in transplant patients: case report showing interference of orlistat with absorption of cyclosporine and review of literature.	2002 Mar-Apr	11942778
Orlistat in the treatment of Type 2 diabetes mellitus.	2002 May	11996637

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dose of XENICAL (orlistat capsule) is one 120-mg capsule three times a day with each main meal containing fat (during or up to 1 hour after the meal).

Route of Administration: Oral

In Vitro Use Guide

Orlistat inhibited cell proliferation by 61 % in ECC-1 cells and 57 % in KLE cells at a dose of 500 μM

Name

Type

Language

ORLISTAT

Official Name

English

ALLI

Preferred Name

English

ORLISTAT [USP-RS]

Common Name

English

ORLISTAT [USP MONOGRAPH]

Common Name

English

ORLISTAT [MART.]

Common Name

English

Orlistat [WHO-DD]

Common Name

English

RO-180647-002

Code

English

XENICAL

Brand Name

English

orlistat [INN]

Common Name

English

RO-18-0647/002

Code

English

RO 18-0647/002

Code

English

L-LEUCINE, N-FORMYL-, 1-((3-HEXYL-4-OXO-2-OXETANYL)METHYL)DODECYL ESTER, (2S-(2.ALPHA.(R*),3.BETA.))-

Common Name

English

ORLISTAT [JAN]

Common Name

English

ORLISTAT [USAN]

Common Name

English

ORLISTAT [VANDF]

Common Name

English

N-FORMYL-L-LEUCINE, ESTER WITH (3S,4S)-3-HEXYL-4-((2S)-2-HYDROXYTRIDECYL)-2-OXETANONE

Common Name

English

NSC-758881

Code

English

ORLISTAT [ORANGE BOOK]

Common Name

English

ORLISTAT [HSDB]

Common Name

English

RO-180647002

Code

English

ORLISTAT [EMA EPAR]

Common Name

English

ORLISTAT [MI]

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000009916