OTENABANT

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C25H25Cl2N7O
Molecular Weight	510.418
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

CCNC1(CCN(CC1)C2=NC=NC3=C2N=C(N3C4=CC=C(Cl)C=C4)C5=CC=CC=C5Cl)C(N)=O

InChI

InChIKey=UNAZAADNBYXMIV-UHFFFAOYSA-N

InChI=1S/C25H25Cl2N7O/c1-2-31-25(24(28)35)11-13-33(14-12-25)22-20-23(30-15-29-22)34(17-9-7-16(26)8-10-17)21(32-20)18-5-3-4-6-19(18)27/h3-10,15,31H,2,11-14H2,1H3,(H2,28,35)

HIDE SMILES / InChI

Molecular Formula	C25H25Cl2N7O
Molecular Weight	510.418
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description

Otenabant (CP-945,598) is Pfizer developed as a potent and selective cannabinoid receptor CB1 antagonist with Ki of 0.7 nM, which exhibits 10,000-fold greater selectivity against human CB2 receptor, for treatment of obesity. In clinical trial III Pfizer decided to discontinue the development program based on changing regulatory perspectives on the risk/benefit profile of the CB1 class and likely new regulatory requirements for approval.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cannabinoid CB1 receptor 85	Antagonist 2,778		0.7 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Obesity 203	Primary		Phase III 656	Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
14 ng/mL	25 mg single, oral		OTENABANT serum	Homo sapiens
42 ng/mL	25 mg single, oral		N-DESETHYL OTENABANT serum	Homo sapiens

AUC

Value	Dose	Co-administered	Analyte	Population
0.01 ng × h/mL	25 mg single, oral		OTENABANT serum	Homo sapiens
3966 ng × h/mL	25 mg single, oral		N-DESETHYL OTENABANT serum	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
159 h	25 mg single, oral		OTENABANT serum	Homo sapiens
139 h	25 mg single, oral		N-DESETHYL OTENABANT serum	Homo sapiens

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1,737 inhibitor 1,587	inhibitor 1,767 substrate 1,037	substrate 1,217 inhibitor 1,852	inhibitor 1,612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP2C19 991 CYP3A5 395 CYP1A1 349 CYP2E1 667 CYP1A2 1,054 CYP2C8 693 P-gp 1,537

Drug as perpetrator

Show entries

Target	Modality	Activity
CYP3A4 1,925	inhibitor 3,277	no
CYP2D6 1,891	inhibitor 3,277	yes [IC50 16.933 uM]
CYP2C9 1,819	inhibitor 3,277	yes [IC50 2.1317 uM]

Showing 1 to 3 of 3 entries

Previous1Next

Drug as victim

Show entries

Target	Modality	Activity
CYP3A4 1,737	substrate 3,367	major
CYP3A5 395	substrate 3,367	major
CYP1A1 349	substrate 3,367	no
CYP1A2 1,054	substrate 3,367	no
CYP2C19 991	substrate 3,367	no

Showing 1 to 5 of 10 entries

Previous1 2Next

Tox targets

Show entries

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1,647	inhibitor 1,626

Showing 1 to 1 of 1 entries

Previous1Next

Sourcing

Sourcing

Show entries

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P003PJF	https://www.1pchem.com/search?query=1P003PJF
1PlusChem LLC	1P00FCHE	https://www.1pchem.com/search?query=1P00FCHE
AK Scientific	Y0367	https://aksci.com/item_detail.php?cat=Y0367
AK Scientific	Y0444	https://aksci.com/item_detail.php?cat=Y0444
AbovChem LLC	HY-10871A	http://www.abovchem.com/pc/en/product_list.aspx?wd=HY-10871A

Showing 1 to 5 of 49 entries

Previous1 2 3 4 5…10Next

PubMed

Title	Date	PubMed
No data available in table

Patents

Sample Use Guides

In Vivo Use Guide

Three double-blind, placebo-controlled, three-parallel-group, multicenter phase 3 trials were conducted to assess the efficacy and safety of CP-945,598 (OTENABANT) for weight loss and weight-loss maintenance. In total, 1,253 and 2,536 participants in the two 2-year multinational and North American studies were randomized to 10-mg CP-945,598 (n = 360; 718); 20-mg CP-945,598 (n = 534, 1,084) and placebo (n = 359, 734), respectively; and 975 participants were randomized to 10-mg CP-945,598 (n = 318); 20-mg CP-945,598 (n = 320); and placebo (n = 337) in the 1-year multinational diabetes trial.

Route of Administration: Oral

In Vitro Use Guide

CP-945,598 (TENABANT) exhibits sub-nanomolar potency at human CB(1) receptors in both binding (K(i)=0.7 nM) and functional assays (K(i)=0.2 nM). The compound has low affinity (K(i)=7600 nM) for human CB(2) receptors.

Substance Class	Chemical
Record UNII	J8211Y53EF
Record Status	`Validated (UNII)`
Record Version

Show entries

Name

Type

Language

OTENABANT

Official Name

English

CP-945,598

Code

English

OTENABANT [USAN]

Common Name

English

4-PIPERIDINECARBOXAMIDE, 1-(8-(2-CHLOROPHENYL)-9-(4-CHLOROPHENYL)-9H-PURIN-6-YL)-4- (ETHYLAMINO)-

Systematic Name

English

CP-945598

Code

English

Showing 1 to 5 of 8 entries

Previous1 2Next

Show entries

Classification Tree

Code System

Code

Agent Affecting Nervous System

NCI_THESAURUS

C29728

Showing 1 to 1 of 1 entries

Previous1Next

Show entries

Code System

Code

Type

Description

EPA CompTox

DTXSID20988316

PRIMARY

ChEMBL

CHEMBL562668

PRIMARY

FDA UNII

J8211Y53EF

PRIMARY

SMS_ID

100000127535

PRIMARY

EVMPD

SUB33607

PRIMARY

Showing 1 to 5 of 12 entries

Previous1 2 3Next

Show entries

Related Record

Type

Details


					J8211Y53EF

OTENABANT

EXCRETED UNCHANGED

Qualification:

FECAL; URINE

Amount:

2 % (average)
of the dose


					805SU96HKF

CYTOCHROME P450 3A5

METABOLIC ENZYME -> SUBSTRATE


					NJ1Q2Q7LO5

CANNABINOID RECEPTOR 1

TARGET -> INHIBITOR


					PUO0521HZV

CYTOCHROME P450 3A4

METABOLIC ENZYME -> SUBSTRATE

Interaction Type:

MAJOR


					X2166Z319O

OTENABANT HYDROCHLORIDE

SALT/SOLVATE -> PARENT

Showing 1 to 5 of 5 entries

Previous1Next

Show entries

Related Record

Type

Details


					Y0KJG11PJR

CE-114764

METABOLITE -> PARENT

Interaction Type:

MAJOR

Qualification:

FECAL

Amount:

30.9 % [16.1 to 45.7] (average)
of the dose


					6R4ERM9B2E

1-(8-(2-CHLOROPHENYL)-9-(4-CHLOROPHENYL)-9H-PURIN-6-YL)-4-(HYDROXYAMINO)-4-PIPERIDINECARBOXAMIDE

METABOLITE -> PARENT

Qualification:

URINE

Amount:

0.6 % [0.5 to 0.7] (average)
of the dose


					SRU4YD01MF

N-DESETHYL OTENABANT

METABOLITE -> PARENT

Interaction Type:

MAJOR

Qualification:

PLASMA

Amount:

57.3 % (average)
of the extracted circulating radioactivity over 0 to 48 h


					U7XUY5K4AT

4-PIPERIDINONE, 1-(8-(2-CHLOROPHENYL)-9-(4-CHLOROPHENYL)-9H-PURIN-6-YL)-, OXIME

METABOLITE -> PARENT

Qualification:

PLASMA

Amount:

17.9 % (average)
of the extracted circulating radioactivity over 0 to 48 h


					Y0KJG11PJR

CE-114764

METABOLITE -> PARENT

Interaction Type:

MAJOR

Qualification:

URINE

Amount:

5.4 % [3.9 to 6.9] (average)
of the dose

Showing 1 to 5 of 11 entries

Previous1 2 3Next

Show entries

Related Record

Type

Details


					J8211Y53EF

OTENABANT

ACTIVE MOIETY

Showing 1 to 1 of 1 entries

Previous1Next

Name	Property Type	Amount	Parameters
Tmax	PHARMACOKINETIC	6 hours (average)	ORAL ADMINISTRATION SINGLE DOSE 25 mg (average) IN HEALTHY HUMAN SUBJECTS

Biological Half-life	PHARMACOKINETIC	159 hours (average)	ORAL ADMINISTRATION IN HEALTHY HUMAN SUBJECTS SINGLE DOSE 25 mg (average)

SMILES

InChI

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Tox targets

Sourcing

PubMed

Patents

Sample Use Guides

C_max

T_1/2

Drug as perpetrator