PF-05175157

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C23H27N5O2
Molecular Weight	405.4928
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)N1N=CC2=C1C(=O)CC3(CCN(CC3)C(=O)C4=CC5=C(C=C4)N=C(C)N5)C2

InChI

InChIKey=BDXXSFOJPYSYOC-UHFFFAOYSA-N

InChI=1S/C23H27N5O2/c1-14(2)28-21-17(13-24-28)11-23(12-20(21)29)6-8-27(9-7-23)22(30)16-4-5-18-19(10-16)26-15(3)25-18/h4-5,10,13-14H,6-9,11-12H2,1-3H3,(H,25,26)

HIDE SMILES / InChI

Molecular Formula	C23H27N5O2
Molecular Weight	405.4928
Charge	0
Count

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

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/30999821 | https://www.ncbi.nlm.nih.gov/pubmed/27997806 | https://adisinsight.springer.com/drugs/800033777

PF-05175157 exhibited good potencies against the two isoforms of the Acetyl-CoA carboxylase enzyme (ACC1 and ACC2) from human and rat. PF-05175157 has undergone multiple clinical trials in healthy volunteers and for the treatment of diabetes mellitus. PF-05175157 was in the phase II when the development was discontinued due to safety concerns. Among potential barriers for the use of ACC inhibitors in humans include concerns of increased risk of myocardial injury following an ischemic event. PF-05175157 reduced the multiplication of West Nile virus (WNV), dengue virus (DENV), and Zika virus (ZIKV) in cultured cells, which is compatible with the predicted broad spectrum of host targeting antivirals. PF-05175157 reduced the peak of viremia in WNV-infected mice, supporting that ACC is a valuable target for antiviral intervention. PF05175157 also reduced the viral burden in the kidney of infected mice.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Acetyl-CoA carboxylase 1 5 Target ID: CHEMBL2397 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25423286	Inhibitor 8504		27.0 nM [IC50]
Acetyl-CoA carboxylase 2 2 Target ID: CHEMBL4829 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25423286	Inhibitor 8504		33.0 nM [IC50]

C_max

Value	Dose	Co-administered	Analyte	Population
390 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32809824/	5 mg/kg single, oral dose: 5 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		PF-05175157 plasma	Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: FASTED
5780 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32809824/	5 mg/kg single, oral dose: 5 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		PF-05175157 plasma	Macaca fascicularis population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
965 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32809824/	1 mg/kg single, intravenous dose: 1 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	PF-05175157 plasma	Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
2490 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32809824/	5 mg/kg single, oral dose: 5 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	PF-05175157 plasma	Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: FASTED
36200 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32809824/	5 mg/kg single, oral dose: 5 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	PF-05175157 plasma	Macaca fascicularis population: HEALTHY age: ADULT sex: MALE food status: FASTED
14000 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32809824/	1 mg/kg single, intravenous dose: 1 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	PF-05175157 plasma	Macaca fascicularis population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
8.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32809824/	1 mg/kg single, intravenous dose: 1 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	PF-05175157 plasma	Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
5.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32809824/	5 mg/kg single, oral dose: 5 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	PF-05175157 plasma	Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: FASTED
11 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32809824/	5 mg/kg single, oral dose: 5 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	PF-05175157 plasma	Macaca fascicularis population: HEALTHY age: ADULT sex: MALE food status: FASTED
11 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32809824/	1 mg/kg single, intravenous dose: 1 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	PF-05175157 plasma	Macaca fascicularis population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
0.96% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32809824/	1 mg/kg single, intravenous dose: 1 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		PF-05175157 plasma	Macaca fascicularis population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
3.9% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32809824/	10 mg/kg single, oral dose: 10 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		PF-05175157 plasma	Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: FASTED

PubMed

Title	Date	PubMed
Targeting host metabolism by inhibition of acetyl-Coenzyme A carboxylase reduces flavivirus infection in mouse models.	2019	30999821
Discontinued drug therapies to treat diabetes in 2015.	2017-02	27997806
Synthesis, Biological Evaluation and Molecular Docking Studies of Piperidinylpiperidines and Spirochromanones Possessing Quinoline Moieties as Acetyl-CoA Carboxylase Inhibitors.	2015-09-07	26370948
Decreasing the rate of metabolic ketone reduction in the discovery of a clinical acetyl-CoA carboxylase inhibitor for the treatment of diabetes.	2014-12-26	25423286

Sample Use Guides

In Vivo Use Guide

20 mg/kg twice a day

Route of Administration: Oral

Substance Class	Chemical Created by `admin` on `Mon Mar 31 20:56:50 GMT 2025` Edited by `admin` on `Mon Mar 31 20:56:50 GMT 2025`
Record UNII	P826WR56FI
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

SPIRO(5H-INDAZOLE-5,4'-PIPERIDIN)-7(6H)-ONE, 1,4-DIHYDRO-1'-((2-METHYL-1H-BENZIMIDAZOL-6-YL)CARBONYL)-1-(1-METHYLETHYL)-

Preferred Name

English

PF-05175157

Common Name

English

Code System Code Type Description

DRUG BANK

DB12096