DIRLOTAPIDE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C40H33F3N4O3
Molecular Weight	674.7102
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN(CC1=CC=CC=C1)C(=O)[C@@H](NC(=O)C2=CC3=C(C=CC(NC(=O)C4=C(C=CC=C4)C5=CC=C(C=C5)C(F)(F)F)=C3)N2C)C6=CC=CC=C6

InChI

InChIKey=TUOSYWCFRFNJBS-BHVANESWSA-N

InChI=1S/C40H33F3N4O3/c1-46(25-26-11-5-3-6-12-26)39(50)36(28-13-7-4-8-14-28)45-38(49)35-24-29-23-31(21-22-34(29)47(35)2)44-37(48)33-16-10-9-15-32(33)27-17-19-30(20-18-27)40(41,42)43/h3-24,36H,25H2,1-2H3,(H,44,48)(H,45,49)/t36-/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.zoetisus.com/contact/pages/product_information/msds_pi/pi/slentrol.pdf
Curator's Comment: description was created based on several sources, including: https://www.vetdepot.com/product-labels/slentrol.pdf | https://www.ncbi.nlm.nih.gov/pubmed/17276061 | https://www.ncbi.nlm.nih.gov/pubmed/17567511

Dirlotapide is indicated for the management of obesity in dogs. Dirlotapide is a microsomal triglyceride transfer protein (MTP) inhibitor. It mainly acts locally in the gut to reduce appetite, increase fecal fat and produce weight loss in dogs. The adverse reactions associated with treatment with Dirlotapide include vomiting, loose stools/diarrhea, lethargy, and anorexia.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Microsomal triglyceride transfer protein 2 Target ID: CHEMBL2364681 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17276061	Inhibitor 8504	1.5 nM [IC50]
Cytochrome P450 1A2 73 Target ID: CHEMBL3356 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17276061	Inhibitor 8504
Cytochrome P450 2C9 50 Target ID: CHEMBL3397 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17276061	Inhibitor 8504
Cytochrome P450 2C19 51 Target ID: CHEMBL3622 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17276061	Inhibitor 8504
Cytochrome P450 2D6 62 Target ID: CHEMBL289 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17276061	Inhibitor 8504
Cytochrome P450 3A 22 Target ID: CHEMBL2364675 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17276061	Inhibitor 8504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Obesity 206 Sources: https://www.vetdepot.com/product-labels/slentrol.pdf	Primary		Approved 8583	SLENTROL Approved Use SLENTROL (dirlotapide) Oral Solution is indicated for the management of obesity in dogs. Launch Date 2007

PubMed

Title	Date	PubMed
Low-energy nanoemulsification to design veterinary controlled drug delivery devices.	2010-10-21	21042549
The use of 18O-exchange and base-catalyzed N-dealkylation with liquid chromatography/tandem mass spectrometry to identify carbinolamide metabolites.	2010-07-30	20552706
Identification of the transcriptional response of human intestinal mucosa to Lactobacillus plantarum WCFS1 in vivo.	2008-08-05	18681965
Efficacy and safety of dirlotapide in the management of obese dogs evaluated in two placebo-controlled, masked clinical studies in North America.	2007-08	17567518
An evaluation of dirlotapide to reduce body weight of client-owned dogs in two placebo-controlled clinical studies in Europe.	2007-08	17567517
Influence of dirlotapide, a microsomal triglyceride transfer protein inhibitor, on the digestibility of a dry expanded diet in adult dogs.	2007-08	17567516
Evaluation of dirlotapide for sustained weight loss in overweight Labrador retrievers.	2007-08	17567515
The safety of dirlotapide in dogs.	2007-08	17567514
Biologic activity of dirlotapide, a novel microsomal triglyceride transfer protein inhibitor, for weight loss in obese dogs.	2007-08	17567513
Pharmacokinetics of dirlotapide in the dog.	2007-08	17567512
Absorption, distribution, metabolism, and excretion of dirlotapide in the dog.	2007-08	17567511
Dirlotapide: a review of its properties and role in the management of obesity in dogs.	2007-08	17567510
Canine obesity: an overview.	2007-08	17567509
Dirlotapide, a U.S. Food and Drug Administration-approved first-in-class obesity drug for dogs-will humans be next?	2007-05	19885086
In vitro and in vivo profile of 5-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-1H-indole-2-carboxylic acid benzylmethyl carbamoylamide (dirlotapide), a novel potent MTP inhibitor for obesity.	2007-04-01	17276061

Patents

Sample Use Guides

In Vivo Use Guide

The initial dosage of SLENTROL is 0.01 mL/kg (0.0045 mL/lb) body weight, administered once daily, for the first 14 days. After the first 14 days of treatment, the dose volume of SLENTROL should be doubled to 0.02 mL/kg (0.009 mL/lb) of body weight, administered once daily for the next 14 days (days 15 to 28 of treatment). Dogs should be weighed monthly and the dose volume adjusted every month, as necessary, to maintain a target percent weight loss of ≥0.7% per week.

Route of Administration: Oral

In Vitro Use Guide

In a murine model investigating intestinal triglyceride transfer protein (MTP) inhibition, dirlotapide demonstrated potent inhibition of intestinal fat absorption with an ED25 of 0.16 mg/kg. In contrast, it was a poor inhibitor of hepatic MTP as demonstrated in a murine model of triglyceride lowering, where it had an ED25 of 6 mg/kg.

Name

Type

Language

DIRLOTAPIDE

Official Name

English

SLENTROL

Preferred Name

English

CP-742,033

Code

English

1H-INDOLE-2-CARBOXAMIDE, 1-METHYL-N-((1S)-2-(METHYL(PHENYLMETHYL)AMINO)-2-OXO-1-PHENYLETHYL)-5-(((4'-(TRIFLUOROMETHYL)(1,1'-BIPHENYL)-2-YL)CARBONYL)AMINO)-

Common Name

English

CP-742033

Code

English

DIRLOTAPIDE [GREEN BOOK]

Common Name

English

dirlotapide [INN]

Common Name

English

N-((1S)-2-(BENZYLMETHYLAMINO)-2-OXO-1-PHENYLETHYL)-1-METHYL-5-(((4'-(TRIFLUOROMETHYL)BIPHENYL-2-YL)CARBONYL)AMINO)-1H-INDOLE-2-CARBOXAMIDE

Common Name

English

DIRLOTAPIDE [USAN]

Common Name

English

DIRLOTAPIDE [EMA EPAR VETERINARY]

Common Name

English

DIRLOTAPIDE [MI]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29728