FENCLOZIC ACID

Possibly Marketed Outside US

Details

Stereochemistry	ACHIRAL
Molecular Formula	C11H8ClNO2S
Molecular Weight	253.705
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)CC1=CSC(=N1)C2=CC=C(Cl)C=C2

InChI

InChIKey=APBSKHYXXKHJFK-UHFFFAOYSA-N

InChI=1S/C11H8ClNO2S/c12-8-3-1-7(2-4-8)11-13-9(6-16-11)5-10(14)15/h1-4,6H,5H2,(H,14,15)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/4190640 | https://www.ncbi.nlm.nih.gov/pubmed/23609606 | https://www.ncbi.nlm.nih.gov/pubmed/27896398 | Scherrer, R.. (2012) Anti-inflammatory Agents Part I, page 118, retrieved from: https://books.google.ru/books?id=-DZRx_kaaCMC

Fenclozic acid emerged in the late 1960s as a promising carboxylic acid non-steroidal anti-inflammatory drug candidate that demonstrated potent anti-inflammatory, anti-pyretic and analgesic properties. Whole body autoradiography showed fenclozic acid distribution into all tissues except the brain, with radioactivity still detectable in blood, kidney and liver at 72 h post-dose. Fenclozic acid was compared with aspirin in a double-blind, crossover trial in patients with rheumatoid arthritis. It was concluded that fenclozic acid afforded symptomatic relief and was comparable to aspirin. Unfortunately, hepatotoxicity was observed in subsequent trials and the drug was withdrawn from the clinic.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cytochrome P450 1A2 73 Target ID: CHEMBL3356 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23609606	Inhibitor 8504
Cyclooxygenase 89 Target ID: CHEMBL2094253 Sources: http://adisinsight.springer.com/drugs/800000957	Inhibitor 8504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Rheumatoid arthritis 320 Sources: https://www.ncbi.nlm.nih.gov/pubmed/4190640 https://www.ncbi.nlm.nih.gov/pubmed/4903319 https://www.ncbi.nlm.nih.gov/pubmed/4903318	Palliative		Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
13.6 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4903318/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	FENCLOZIC ACID serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
55.2 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4903318/	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	FENCLOZIC ACID serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
84.2 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4903318/	150 mg 2 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered:	FENCLOZIC ACID serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
25 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4903318/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	FENCLOZIC ACID serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
23 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4903318/	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	FENCLOZIC ACID serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
45.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4903318/	150 mg 2 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered:	FENCLOZIC ACID serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
400 mg 2 times / day multiple, oral Highest studied dose Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/4903319/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/4903319/	Other AEs: Tinnitus, Headache... Other AEs: Tinnitus (4.2%) Headache (4.2%) Drowsiness (4.2%) Urinary frequency (4.2%) Gastrointestinal disturbances (29.2%) Sources: https://pubmed.ncbi.nlm.nih.gov/4903319/
400 mg single, oral Highest studied dose Dose: 400 mg Route: oral Route: single Dose: 400 mg Sources: https://pubmed.ncbi.nlm.nih.gov/4903318/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/4903318/	Sources: https://pubmed.ncbi.nlm.nih.gov/4903318/

AEs

AE	Significance	Dose	Population
Gastrointestinal disturbances	29.2%	400 mg 2 times / day multiple, oral Highest studied dose Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/4903319/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/4903319/
Drowsiness	4.2%	400 mg 2 times / day multiple, oral Highest studied dose Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/4903319/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/4903319/
Headache	4.2%	400 mg 2 times / day multiple, oral Highest studied dose Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/4903319/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/4903319/
Tinnitus	4.2%	400 mg 2 times / day multiple, oral Highest studied dose Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/4903319/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/4903319/
Urinary frequency	4.2%	400 mg 2 times / day multiple, oral Highest studied dose Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/4903319/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/4903319/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 1087 inhibitor 2252	inhibitor 2438	inhibitor 2507	substrate 9

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
BSEP 550 CYP2C19 2057 CYP19A1 429 CYP1A2 2153 MRP2 499	P-gp 2052

Drug as perpetrator

Target	Modality	Activity
BSEP 554	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw2MDIwIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDE5MDkyODIifX0=	no [IC50 >1000 uM]
MRP2 625	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/23609606/	no [IC50 >1000 uM]
CYP19A1 430	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/28858#section=Biological-Test-Results Page: 44.0	no
CYP1A2 2333	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/28858#section=Biological-Test-Results Page: 100.0	no
CYP2C19 2141	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/28858#section=Biological-Test-Results Page: 100.0	no
CYP2C9 2497	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/28858#section=Biological-Test-Results Page: 93.0	no
CYP2D6 2546	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/28858#section=Biological-Test-Results Page: 95.0	no
CYP3A4 2633	inducer 1966 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/28858#section=Biological-Test-Results Page: 87.0	no
CYP3A4 2633	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/28858#section=Biological-Test-Results Page: 90.0	no

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 2052	substrate 4014 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/28858#section=Biological-Test-Results Page: 89 \| 90	inconclusive

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	substrate 9 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/28858#section=Biological-Test-Results Page: 27.0

PubMed

Title	Date	PubMed
Acute liver effects, disposition and metabolic fate of [14C]-fenclozic acid following oral administration to normal and bile-cannulated male C57BL/6J mice.	2017-07	27896398
A correlation between the in vitro drug toxicity of drugs to cell lines that express human P450s and their propensity to cause liver injury in humans.	2014-01	24085192
In vitro exploration of potential mechanisms of toxicity of the human hepatotoxic drug fenclozic acid.	2013-08	23609606

Patents

Sample Use Guides

In Vivo Use Guide

200, 300 or 400 mg daily for a period of 10 days

Route of Administration: Oral

In Vitro Use Guide

Partial inhibition of the activities of the biliary efflux transporters BSEP and Mrp2 activities was observed, this was evident only at very high concentrations of fenclozic acid (apparent IC50 ≥ 1,000 uM).

Name

Type

Language

FENCLOZIC ACID

Official Name

English

I.C.I. 54,450

Preferred Name

English

FENCLOZIC ACID [MI]

Common Name

English

fenclozic acid [INN]

Common Name

English

2-(P-CHLOROPHENYL)-4-THIAZOLEACETIC ACID

Common Name

English

ICI-54450

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C1323