TALNIFLUMATE

Possibly Marketed Outside US

Details

Stereochemistry	RACEMIC
Molecular Formula	C21H13F3N2O4
Molecular Weight	414.3341
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

FC(F)(F)C1=CC(NC2=NC=CC=C2C(=O)OC3OC(=O)C4=C3C=CC=C4)=CC=C1

InChI

InChIKey=ANMLJLFWUCQGKZ-UHFFFAOYSA-N

InChI=1S/C21H13F3N2O4/c22-21(23,24)12-5-3-6-13(11-12)26-17-16(9-4-10-25-17)19(28)30-20-15-8-2-1-7-14(15)18(27)29-20/h1-11,20H,(H,25,26)

HIDE SMILES / InChI

Description
Sources: http://www.jocpr.com/articles/cluster-and-multilinear-regression-analyses-guided-identification-of-molecular-descriptors-that-account-for-cyclooxygena.pdf
Curator's Comment: description was created based on several sources, including https://www.drugbank.ca/drugs/DB09295 | https://www.drugs.com/international/talniflumate.html | https://www.ncbi.nlm.nih.gov/pubmed/15202731 | https://www.ncbi.nlm.nih.gov/pubmed/27879193 | https://www.ncbi.nlm.nih.gov/pubmed/14606981

Talniflumate, a prodrug of niflumic acid, is a potent analgesic and anti-inflammatory drug that has been used for the treatment of rheumatoid diseases. Talniflumate was synthesized by the esterification of a carboxyl group of niflumic acid with the phthalidyl moiety, and it exerts activity in the body through conversion to niflumic acid. Talniflumate has been studied as a mucoregulator for the treatment of cystic fibrosis, chronic obstructive pulmonary disease, and asthma. However, development of these indications appears to have been discontinued. Talniflumate has been approved and marketed for almost 20 years in Argentina and selected other countries (excluding the United States, Europe, and Japan).

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Calcium-activated chloride channel 1 Target ID: CHEMBL2364708 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17604505	Inhibitor 8504
Cyclooxygenase 89 Target ID: CHEMBL2094253 Sources: http://www.jocpr.com/articles/cluster-and-multilinear-regression-analyses-guided-identification-of-molecular-descriptors-that-account-for-cyclooxygena.pdf	Inhibitor 8504

Conditions

Condition	Modality	Highest Phase	Product
Rheumatoid arthritis 320 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14606981/	Primary	Approved 8583	Huluma Approved Use Unknown
Osteoarthritis 157 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14606981/	Primary	Approved 8583	Huluma Approved Use Unknown
Cystic fibrosis 120 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17604505	Primary	Phase II 1147	Huluma Approved Use Unknown

C_max

Value	Dose	Analyte	Population
187.9 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19359802/	740 mg single, oral dose: 740 mg route of administration: Oral experiment type: SINGLE co-administered:	NIFLUMIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
5.7 μg/mL EXPERIMENT https://link.springer.com/article/10.1007/BF02976244	504 mg single, oral dose: 504 mg route of administration: Oral experiment type: SINGLE co-administered:	NIFLUMIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
423 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15470687/	740 mg single, oral dose: 740 mg route of administration: Oral experiment type: SINGLE co-administered:	TALNIFLUMATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
4121 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15470687/	740 mg single, oral dose: 740 mg route of administration: Oral experiment type: SINGLE co-administered:	NIFLUMIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
795.5 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19359802/	740 mg single, oral dose: 740 mg route of administration: Oral experiment type: SINGLE co-administered:	NIFLUMIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
2212 μg × min/mL EXPERIMENT https://link.springer.com/article/10.1007/BF02976244	504 mg single, oral dose: 504 mg route of administration: Oral experiment type: SINGLE co-administered:	NIFLUMIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1752 ng × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15470687/	740 mg single, oral dose: 740 mg route of administration: Oral experiment type: SINGLE co-administered:	TALNIFLUMATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
16296 ng × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15470687/	740 mg single, oral dose: 740 mg route of administration: Oral experiment type: SINGLE co-administered:	NIFLUMIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19359802/	740 mg single, oral dose: 740 mg route of administration: Oral experiment type: SINGLE co-administered:	NIFLUMIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
229.4 min EXPERIMENT https://link.springer.com/article/10.1007/BF02976244	504 mg single, oral dose: 504 mg route of administration: Oral experiment type: SINGLE co-administered:	NIFLUMIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
121 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15470687/	740 mg single, oral dose: 740 mg route of administration: Oral experiment type: SINGLE co-administered:	TALNIFLUMATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
111 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15470687/	740 mg single, oral dose: 740 mg route of administration: Oral experiment type: SINGLE co-administered:	NIFLUMIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
1480 mg 1 times / day multiple, oral Highest studied dose Dose: 1480 mg, 1 times / day Route: oral Route: multiple Dose: 1480 mg, 1 times / day Sources: https://journals.ashs.org/hortsci/view/journals/hortsci/44/1/article-p102.xml	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://journals.ashs.org/hortsci/view/journals/hortsci/44/1/article-p102.xml	Sources: https://journals.ashs.org/hortsci/view/journals/hortsci/44/1/article-p102.xml

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 1087		inhibitor 2507

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
MRP3 246 MRP2 499 MRP4 290 CYP1A2 2153 BSEP 550 CYP2C19 2057 CYP19A1 429	P-gp 2052

Drug as perpetrator

Target	Modality	Activity
CYP2C19 2141	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/48229#section=Biological-Test-Results Page: 1.0	inconclusive [IC50 1.5487 uM]
BSEP 554	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw2MDIwIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDEwODE1MDYifX0=	no [IC50 >133 uM]
MRP2 625	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1NzQ4IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDEwODE1MDYifX0=	no [IC50 >133 uM]
MRP3 326	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1OTE4IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDEwODE1MDYifX0=	no [IC50 >133 uM]
MRP4 345	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNzQzMTI4IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDEwODE1MDYifX0=	no [IC50 >133 uM]
CYP19A1 430	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/48229#section=Biological-Test-Results Page: 53.0	no
CYP2D6 2546	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/48229#section=Biological-Test-Results Page: 101.0	no
CYP3A4 2633	inducer 1966 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/48229#section=Biological-Test-Results Page: 76.0	no
CYP1A2 2333	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/48229#section=Biological-Test-Results Page: 4.0	yes [IC50 9.7717 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 2052	substrate 4014 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/48229#section=Biological-Test-Results Page: 75 \| 78	no

PubMed

Title	Date	PubMed
Talniflumate (Genaera).	2004-05	15202731

Patents

Sample Use Guides

In Vivo Use Guide

370mg, 3 times a day

Route of Administration: Oral

In Vitro Use Guide

Human pancreatic cancer cell line (MIA PaCa and BxPC-3) were used for activity evaluation. Cells were were incubated with different concentrations of Talniflumate (50, 100, 150 and 200 mkM), gefitinib and the combination of talniflumate and gefitinib for 24h. Cell viability was determined using the MTT method.

Name

Type

Language

TALNIFLUMATE

Official Name

English

SOMALGEN

Preferred Name

English

Talniflumate [WHO-DD]

Common Name

English

BA 7602-06

Code

English

BA-7602-06

Code

English

TALNIFLUMATE [MART.]

Common Name

English

TALNIFLUMATE [USAN]

Common Name

English

talniflumate [INN]

Common Name

English

TALNIFLUMATE [MI]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C257