ADP-597

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C21H29N5O6S
Molecular Weight	479.55
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=C(NC2=CC=C(N=C2C)S(C)(=O)=O)N=CN=C1OC3CCN(CC3)C(=O)OC(C)C

InChI

InChIKey=WPDCHTSXOPUOII-UHFFFAOYSA-N

InChI=1S/C21H29N5O6S/c1-13(2)31-21(27)26-10-8-15(9-11-26)32-20-18(30-4)19(22-12-23-20)25-16-6-7-17(24-14(16)3)33(5,28)29/h6-7,12-13,15H,8-11H2,1-5H3,(H,22,23,25)

HIDE SMILES / InChI

Molecular Formula	C21H29N5O6S
Molecular Weight	479.55
Charge	0
Count

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

Description
Sources: https://adisinsight.springer.com/drugs/800029378 | https://www.ncbi.nlm.nih.gov/pubmed/22264481 | https://www.ncbi.nlm.nih.gov/pubmed/21975348

Arena Pharmaceuticals was developing APD-597 (JNJ-38431055), a small molecule, an orally active agonist of the G-protein coupled receptor 119 (GPR119), for the treatment of Type 2 diabetes mellitus. JNJ-38431055 was selected for preclinical development based on a good balance between agonist potency, intrinsic activity and in particular on its good solubility and reduced drug-drug interaction potential. In addition, extensive in vivo studies showed a more favorable metabolic profile that may avoid the generation of long-lasting metabolites with the potential to accumulate in clinical studies. In humans, single-dose oral JNJ-38431055 increased postmeal plasma glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and peptide YY (PYY) concentrations but did not significantly decrease glucose excursion or increase insulin secretion. However, in a graded glucose infusion study, JNJ-38431055 was shown to induce a higher insulin secretion rate (ISR) relative to placebo at elevated plasma glucose levels. These studies provide evidence for the potential efficacy of JNJ-38431055 as an antidiabetes agent in humans.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Glucose-dependent insulinotropic receptor 13 Target ID: CHEMBL5652 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25088191	Agonist 2752		46.0 nM [EC50]
HERG 99 Target ID: CHEMBL240 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22264481	Inhibitor 8504		13000.0 nM [IC50]

C_max

Value	Dose	Analyte	Population
38.8 ng/mL EXPERIMENT https://ascpt.onlinelibrary.wiley.com/doi/epdf/10.1038/clpt.2011.169	2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered:	ADP-597 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
110 ng/mL EXPERIMENT https://ascpt.onlinelibrary.wiley.com/doi/epdf/10.1038/clpt.2011.169	7.5 mg single, oral dose: 7.5 mg route of administration: Oral experiment type: SINGLE co-administered:	ADP-597 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
427 ng/mL EXPERIMENT https://ascpt.onlinelibrary.wiley.com/doi/epdf/10.1038/clpt.2011.169	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	ADP-597 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
393 ng/mL EXPERIMENT https://ascpt.onlinelibrary.wiley.com/doi/epdf/10.1038/clpt.2011.169	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	ADP-597 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
703 ng/mL EXPERIMENT https://ascpt.onlinelibrary.wiley.com/doi/epdf/10.1038/clpt.2011.169	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	ADP-597 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1982 ng/mL EXPERIMENT https://ascpt.onlinelibrary.wiley.com/doi/epdf/10.1038/clpt.2011.169	800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered:	ADP-597 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
221 ng × h/mL EXPERIMENT https://ascpt.onlinelibrary.wiley.com/doi/epdf/10.1038/clpt.2011.169	2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered:	ADP-597 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
628 ng × h/mL EXPERIMENT https://ascpt.onlinelibrary.wiley.com/doi/epdf/10.1038/clpt.2011.169	7.5 mg single, oral dose: 7.5 mg route of administration: Oral experiment type: SINGLE co-administered:	ADP-597 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
2116 ng × h/mL EXPERIMENT https://ascpt.onlinelibrary.wiley.com/doi/epdf/10.1038/clpt.2011.169	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	ADP-597 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
6403 ng × h/mL EXPERIMENT https://ascpt.onlinelibrary.wiley.com/doi/epdf/10.1038/clpt.2011.169	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	ADP-597 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
12791 ng × h/mL EXPERIMENT https://ascpt.onlinelibrary.wiley.com/doi/epdf/10.1038/clpt.2011.169	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	ADP-597 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
34149 ng × h/mL EXPERIMENT https://ascpt.onlinelibrary.wiley.com/doi/epdf/10.1038/clpt.2011.169	800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered:	ADP-597 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
7.1 h EXPERIMENT https://ascpt.onlinelibrary.wiley.com/doi/epdf/10.1038/clpt.2011.169	2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered:	ADP-597 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
7.2 h EXPERIMENT https://ascpt.onlinelibrary.wiley.com/doi/epdf/10.1038/clpt.2011.169	7.5 mg single, oral dose: 7.5 mg route of administration: Oral experiment type: SINGLE co-administered:	ADP-597 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
5.8 h EXPERIMENT https://ascpt.onlinelibrary.wiley.com/doi/epdf/10.1038/clpt.2011.169	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	ADP-597 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
13.5 h EXPERIMENT https://ascpt.onlinelibrary.wiley.com/doi/epdf/10.1038/clpt.2011.169	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	ADP-597 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
13.3 h EXPERIMENT https://ascpt.onlinelibrary.wiley.com/doi/epdf/10.1038/clpt.2011.169	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	ADP-597 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
13 h EXPERIMENT https://ascpt.onlinelibrary.wiley.com/doi/epdf/10.1038/clpt.2011.169	800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered:	ADP-597 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

PubMed

Title	Date	PubMed
Discovery of a second generation agonist of the orphan G-protein coupled receptor GPR119 with an improved profile.	2012-02-15	22264481

Patents

Sample Use Guides

In Vivo Use Guide

Type 2 diabetes mellitus: APD-597 (100 and 500 mg) or sitagliptin (100 mg) as a single-dose or APD-597 (500 mg) once daily for 14 consecutive days were tested.

Route of Administration: Oral

In Vitro Use Guide

APD-597 agonist potency for human GPR119 receptor - EC50 46 nM. APD-597 showed no significant activity in a standard CEREP receptor selectivity panel when tested at 1 uM. In addition, no significant inhibition of hERG channel binding (IC50 >10 uM) was observed and in a patch clamp study APD-597 showed an IC50 of 13 ± 0.2 uM.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 21:30:12 GMT 2025` Edited by `admin` on `Mon Mar 31 21:30:12 GMT 2025`
Record UNII	345354O7AT
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

JNJ-38431055

Preferred Name

English

ADP-597

Common Name

English

4-((6-((6-METHYLSULFONYL-2-METHYLPYRIDIN-3-YL)AMINO)-5-METHOXYPYRIMIDIN-4-YL)OXY)PIPERIDINE-1-CARBOXYLIC ACID ISOPROPYL ESTER

Systematic Name

English

Code System Code Type Description

FDA UNII

345354O7AT