PF-04620110

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C21H24N4O4
Molecular Weight	396.4397
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC1=NC=NC2=C1C(=O)N(CCO2)C3=CC=C(C=C3)[C@H]4CC[C@H](CC(O)=O)CC4

InChI

InChIKey=GEVVQZHMFVFGLN-HDJSIYSDSA-N

InChI=1S/C21H24N4O4/c22-19-18-20(24-12-23-19)29-10-9-25(21(18)28)16-7-5-15(6-8-16)14-3-1-13(2-4-14)11-17(26)27/h5-8,12-14H,1-4,9-11H2,(H,26,27)(H2,22,23,24)/t13-,14-

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23871442 | https://www.ncbi.nlm.nih.gov/pubmed/24900321
Curator's Comment: Description was created based on several sources, including http://adisinsight.springer.com/drugs/800030035

PF-04620110 is an orally active, selective and potent DGAT1 (Acyl-CoA:diacylglycerol acyltransferase 1) inhibitor that inhibits triacylglycerol synthesis in cells and in rodents. PF-04620110 inhibits DGAT-1 with an IC50 of 19 nM and shows high selectivity versus a broad panel of off-target pharmacologic end points. In vivo DGAT-1 inhibition has been demonstrated through reduction of plasma triglyceride levels in rodents at doses of ≥0.1 mg/kg following a lipid challenge. On the basis of this pharmacologic and pharmacokinetic profile, PF-04620110 has been advanced to human clinical studies. PF-4620110 had been in phase I clinical trials by Pfizer for the treatment of type 2 diabetes. But this research was discontinued in 2011.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Diacylglycerol O-acyltransferase 1 7 Target ID: CHEMBL6009 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23871442 \| https://www.ncbi.nlm.nih.gov/pubmed/24900321	Inhibitor 8504		19.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Type 2 diabetes mellitus 262 Sources: https://clinicaltrials.gov/ct2/show/NCT01298518 http://adisinsight.springer.com/drugs/800030035	Primary		Phase I 438	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
91 ng/mL CLINICAL TRIAL https://classic.clinicaltrials.gov/ct2/show/results/NCT01298518	2.5 mg 2 times / day multiple, oral dose: 2.5 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PF-04620110 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
112 ng/mL CLINICAL TRIAL https://classic.clinicaltrials.gov/ct2/show/results/NCT01298518	5 mg 1 times / day multiple, oral dose: 5 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PF-04620110 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
192 mg/mL EXPERIMENT https://journals.physiology.org/doi/epdf/10.1152/ajpgi.00384.2012	21 mg single, oral dose: 21 mg route of administration: Oral experiment type: SINGLE co-administered:	PF-04620110 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
1055 ng × h/mL CLINICAL TRIAL https://classic.clinicaltrials.gov/ct2/show/results/NCT01298518	2.5 mg 2 times / day multiple, oral dose: 2.5 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PF-04620110 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
1027 ng × h/mL CLINICAL TRIAL https://classic.clinicaltrials.gov/ct2/show/results/NCT01298518	5 mg 1 times / day multiple, oral dose: 5 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PF-04620110 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
2330 ng × h/mL EXPERIMENT https://journals.physiology.org/doi/epdf/10.1152/ajpgi.00384.2012	21 mg single, oral dose: 21 mg route of administration: Oral experiment type: SINGLE co-administered:	PF-04620110 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
7.4 h EXPERIMENT https://journals.physiology.org/doi/epdf/10.1152/ajpgi.00384.2012	21 mg single, oral dose: 21 mg route of administration: Oral experiment type: SINGLE co-administered:		PF-04620110 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P008TZM	https://www.1pchem.com/search?query=1P008TZM
eMolecules	206922153	https://orderbb.emolecules.com/search/#?query=206922153
eMolecules	300705538	https://orderbb.emolecules.com/search/#?query=300705538
Molcore	MC115421	http://www.molcore.com/CatMC115421.html
Molnova	M10407	https://www.molnova.com/en/serch-list.html?keywords=M10407
MolPort	MolPort-046-702-047	https://www.molport.com/shop/molecule-link/MolPort-046-702-047
Selleck Chemicals	S7192	http://www.selleckchem.com/search.html?searchDTO.searchParam=S7192

PubMed

Title	Date	PubMed
Discovery of PF-04620110, a Potent, Selective, and Orally Bioavailable Inhibitor of DGAT-1.	2011-05-12	24900321

Patents

Sample Use Guides

In Vivo Use Guide

The five treatments are: A) single dose of 5 mg immediate release tablets in the fasted state; B) single dose of 5 mg modified release osmotic capsule with a short duration of modified release 1 (MR1) in the fasted state; C) single dose of 5 mg modified release osmotic capsule with a long duration of modified release 2 (MR2) in the fasted state; D) single dose of 5 mg modified release osmotic capsule with a short duration of modified release 1 (MR1) in the fed state; E) single dose of 5 mg modified release osmotic capsule with a long duration of modified release 2 (MR2) in the fed state.

Route of Administration: Oral

In Vitro Use Guide

PF-04620110 inhibits human DGAT-1 with an IC50 of 19 nM

Name

Type

Language

PF-04620110

Common Name

English

PF-4620110

Preferred Name

English

CYCLOHEXANEACETIC ACID, 4-(4-(4-AMINO-7,8-DIHYDRO-5-OXOPYRIMIDO(5,4-F)(1,4)OXAZEPIN-6(5H)-YL)PHENYL)-, TRANS-

Systematic Name

English

Code System Code Type Description

DRUG BANK

DB14887