Drug Details

General Information of the Drug (ID: DR2889)
Name
Tolfenamic acid
Synonyms
Clotam; Tolfedine; 2-[(3-Chloro-2-methylphenyl)amino]benzoic Acid; N-(3-Chloro-2-methylphenyl)anthranilic acid; GEA 6414; Acido tolfenamico; Acide tolfenamique; Acidum tolfenamicum; 2-((3-Chloro-2-methylphenyl)amino)benzoic acid; 2-(3-Chloro-2-methylanilino)benzoic acid; N-(2-Methyl-3-chlorophenyl)anthranilic acid; UNII-3G943U18KM; N-(3-Chloro-o-tolyl)-anthranilic acid; Benzoic acid, 2-[(3-chloro-2-methylphenyl)amino]-; Anthranilic acid, N-(3-chloro-o-tolyl)-; N-(3-Chloro-ortho-tolyl) anthranilic acid; CHEBI:32243; 3G943U18KM; NCGC00016705-05; Bifenac; CAS-13710-19-5; DSSTox_CID_25409; DSSTox_RID_80860; DSSTox_GSID_45409; Tolfine; tolfenamic-acid; 2-([3-Chloro-2-methylphenyl]amino)benzoic acid; SR-01000000102; N-(3-Chloro-o-tolyl)anthranilic acid; Tolfenamic; Acide tolfenamique [INN-French]; Acido tolfenamico [INN-Spanish]; Acidum tolfenamicum [INN-Latin]; Tolfenamic acid [INN:BAN:JAN]; Prestwick_579; EINECS 237-264-3; Clotam (TN); TOLFENAMICACID; BRN 0657821; Spectrum_001263; ACMC-209cat; Tolfenamic Acid-13C6; Tolfenamic acid, NSAID; Prestwick0_000205; Prestwick1_000205; Prestwick2_000205; Prestwick3_000205; Spectrum2_001446; Spectrum3_001762; Spectrum4_000238; Spectrum5_001143; Oprea1_692996; SCHEMBL25190; Tolfenamic acid (JAN/INN); BSPBio_000189; BSPBio_003223; KBioGR_000935; KBioSS_001743; flufenamic acid analogue, 32; MLS000028531; BIDD:GT0343; SPECTRUM1501198; SPBio_001311; SPBio_002110; BPBio1_000209; CHEMBL121626; cid_610479; GTPL8769; ZINC2188; DTXSID1045409; BDBM35905; KBio2_001743; KBio2_004311; KBio2_006879; KBio3_002723; YEZNLOUZAIOMLT-UHFFFAOYSA-; HMS1568J11; HMS1921P13; HMS2090D04; HMS2095J11; HMS2230J13; HMS3370A02; HMS3651E06; HMS3712J11; HMS3884M16; Pharmakon1600-01501198; HY-B0335; Tox21_110570; ANW-20211; CCG-39189; MFCD00133865; NSC757873; s1959; SBB058187; AKOS012836098; Tox21_110570_1; 2-(3-Chloro-o-toluidino)benzoic Acid; DB09216; MCULE-9901889833; NSC-757873; 2(3-Chloro-2-methylanilino)benzoic acid; NCGC00016705-01; NCGC00016705-02; NCGC00016705-03; NCGC00016705-04; NCGC00016705-06; NCGC00016705-07; NCGC00016705-10; NCGC00022587-03; NCGC00022587-04; NCGC00022587-05; AK305709; AS-13748; DA-11289; n-(3-chloro-ortho-tolyl)anthranilic acid; SMR000058289; SBI-0051687.P002; AB0032595; 2-(3-Chloro-2-methylanilino)benzoic acid #; AB00052244; FT-0652603; ST51015128; SW196753-3; UNM000001237003; X5948; 2-(3-chloro-2-methylphenylamino)benzoic acid; D01183; J10240; Q59412; AB00052244-15; AB00052244_16; AB00052244_17; A807198; Benzoic acid, 2-(3-chloro-2-methylphenylamino)-; 2-[(3-chloranyl-2-methyl-phenyl)amino]benzoic acid; J-006962; SR-01000000102-2; SR-01000000102-3; Tolfenamic acid, VETRANAL(TM), analytical standard; BRD-K50133271-001-05-4; BRD-K50133271-001-10-4; Benzoic acid, 2-((3-chloro-2-methylphenyl)amino)- (9CI); Tolfenamic acid, European Pharmacopoeia (EP) Reference Standard; Tolfenamic Acid, Pharmaceutical Secondary Standard; Certified Reference Material
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Molecular Type
Small molecule
Disease Pancreatic cancer [ICD-11: 2C10] Investigative [1]
Structure
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2D MOL

3D MOL

ADMET Property
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 5 h
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability
Bioavailability
The bioavailability of drug is 48%
Clearance
The drug present in the plasma can be removed from the body at the rate of 2.37 mL/min/kg
Elimination
Most of the elimination occurs by extrarenal mechanisms in which the unchanged drug together with its glucuronide in urine accounts for only 8.8% of the administered dose
Half-life
The concentration or amount of drug in body reduced by one-half in 8.01 - 13.50 hours
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 21.8344 micromolar/kg/day
Unbound Fraction
The unbound fraction of drug in plasma is 0.003%
Vd
The volume of distribution (Vd) of drug is 1.79-3.2 L/kg
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Formula
C14H12ClNO2
PubChem CID
610479
Canonical SMILES
CC1=C(C=CC=C1Cl)NC2=CC=CC=C2C(=O)O
InChI
1S/C14H12ClNO2/c1-9-11(15)6-4-8-12(9)16-13-7-3-2-5-10(13)14(17)18/h2-8,16H,1H3,(H,17,18)
InChIKey
YEZNLOUZAIOMLT-UHFFFAOYSA-N
CAS Number
CAS 13710-19-5
DrugBank ID
DB09216
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Natural Product(s) Able to Enhance the Efficacy of This Drug
          Curcumin      Hellenia speciosa     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression BIRC5  Molecule Info 
Pathway MAP
Up-regulation Activity CASP3  Molecule Info 
Pathway MAP
Up-regulation Activity CASP7  Molecule Info 
Pathway MAP
Down-regulation Expression p105  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
Down-regulation Expression PSG1  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Induction Loss of mitochondrial membrane potential
Up-regulation ROS generation
                    In-vitro Model HCT 116 CVCL_0291 Colon carcinoma Homo sapiens
HT-29 CVCL_0320 Colon adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Thioridazine plus curcumin induces proteasome activity by up-regulating PSMA5 expression via NOX4-mediated ROS production and that down-regulation of c-FLIP and Mcl-1 expression post-translationally is involved in apoptosis.
          Vincristine      Catharanthus roseus     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression BIRC5  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Induction Cell cycle arrest in G2/M phase
                    In-vitro Model Daoy CVCL_1167 Medulloblastoma Homo sapiens
D283 Med CVCL_1155 Medulloblastoma Homo sapiens
                    Experimental
                    Result(s)		 Combination of clotam and vincristine enhances anti-proliferative effect in medulloblastoma cells.
Target and Pathway
Target(s) DNA-binding factor KBF1 (p105)  Molecule Info  [4]
KEGG Pathway MAPK signaling pathway Click to Show/Hide
2 Ras signaling pathway
3 cAMP signaling pathway
4 Chemokine signaling pathway
5 NF-kappa B signaling pathway
6 HIF-1 signaling pathway
7 Sphingolipid signaling pathway
8 PI3K-Akt signaling pathway
9 Apoptosis
10 Osteoclast differentiation
11 Toll-like receptor signaling pathway
12 NOD-like receptor signaling pathway
13 RIG-I-like receptor signaling pathway
14 Cytosolic DNA-sensing pathway
15 T cell receptor signaling pathway
16 B cell receptor signaling pathway
17 TNF signaling pathway
18 Neurotrophin signaling pathway
19 Prolactin signaling pathway
20 Adipocytokine signaling pathway
21 Non-alcoholic fatty liver disease (NAFLD)
22 Cocaine addiction
23 Epithelial cell signaling in Helicobacter pylori infection
24 Shigellosis
25 Salmonella infection
26 Pertussis
27 Legionellosis
28 Leishmaniasis
29 Chagas disease (American trypanosomiasis)
30 Toxoplasmosis
31 Amoebiasis
32 Tuberculosis
33 Hepatitis C
34 Hepatitis B
35 Measles
36 Influenza A
37 HTLV-I infection
38 Herpes simplex infection
39 Epstein-Barr virus infection
40 Pathways in cancer
41 Transcriptional misregulation in cancer
42 Viral carcinogenesis
43 MicroRNAs in cancer
44 Pancreatic cancer
45 Prostate cancer
46 Chronic myeloid leukemia
47 Acute myeloid leukemia
48 Small cell lung cancer
49 Inflammatory bowel disease (IBD)
NetPath Pathway IL5 Signaling Pathway Click to Show/Hide
2 IL1 Signaling Pathway
3 TCR Signaling Pathway
4 IL2 Signaling Pathway
5 TNFalpha Signaling Pathway
6 Leptin Signaling Pathway
Panther Pathway Apoptosis signaling pathway Click to Show/Hide
2 T cell activation
Pathwhiz Pathway Intracellular Signalling Through Adenosine Receptor A2a and Adenosine Click to Show/Hide
2 Intracellular Signalling Through Adenosine Receptor A2b and Adenosine
Pathway Interaction Database Fc-epsilon receptor I signaling in mast cells Click to Show/Hide
2 BCR signaling pathway
3 LPA receptor mediated events
4 Atypical NF-kappaB pathway
5 Canonical NF-kappaB pathway
6 CD40/CD40L signaling
7 IL12-mediated signaling events
8 Alternative NF-kappaB pathway
9 Osteopontin-mediated events
10 Angiopoietin receptor Tie2-mediated signaling
11 Signaling events mediated by HDAC Class I
12 Regulation of Telomerase
13 IL1-mediated signaling events
14 Glucocorticoid receptor regulatory network
15 TNF receptor signaling pathway
16 IL2 signaling events mediated by PI3K
17 Ceramide signaling pathway
18 amb2 Integrin signaling
19 IL23-mediated signaling events
20 HIV-1 Nef: Negative effector of Fas and TNF-alpha
21 EPO signaling pathway
Reactome Activation of NF-kappaB in B cells Click to Show/Hide
2 RIP-mediated NFkB activation via ZBP1
3 Regulated proteolysis of p75NTR
4 NF-kB is activated and signals survival
5 Senescence-Associated Secretory Phenotype (SASP)
6 FCERI mediated NF-kB activation
7 DEx/H-box helicases activate type I IFN and inflammatory cytokines production
8 Transcriptional regulation of white adipocyte differentiation
9 TAK1 activates NFkB by phosphorylation and activation of IKKs complex
10 Interleukin-1 processing
11 IKBKG deficiency causes anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) (via TLR)
12 IkBA variant leads to EDA-ID
13 CLEC7A (Dectin-1) signaling
14 CD209 (DC-SIGN) signaling
15 CLEC7A/inflammasome pathway
16 MAP3K8 (TPL2)-dependent MAPK1/3 activation
17 TRAF6 mediated NF-kB activation
WikiPathways Toll-like receptor signaling pathway Click to Show/Hide
2 DNA Damage Response (only ATM dependent)
3 SIDS Susceptibility Pathways
4 TCR Signaling Pathway
5 Notch Signaling Pathway
6 TGF Beta Signaling Pathway
7 Oxidative Stress
8 IL-4 Signaling Pathway
9 Apoptosis Modulation by HSP70
10 MAPK Signaling Pathway
11 Myometrial Relaxation and Contraction Pathways
12 IL1 and megakaryotyces in obesity
13 Apoptosis-related network due to altered Notch3 in ovarian cancer
14 Hair Follicle Development: Cytodifferentiation (Part 3 of 3)
15 Hair Follicle Development: Organogenesis (Part 2 of 3)
16 Hair Follicle Development: Induction (Part 1 of 3)
17 Selenium Metabolism and Selenoproteins
18 Cardiac Hypertrophic Response
19 Cytosolic sensors of pathogen-associated DNA
20 Fc epsilon receptor (FCERI) signaling
21 Transcriptional Regulation of White Adipocyte Differentiation
22 Signaling by the B Cell Receptor (BCR)
23 TAK1 activates NFkB by phosphorylation and activation of IKKs complex
24 Structural Pathway of Interleukin 1 (IL-1)
25 EBV LMP1 signaling
26 Aryl Hydrocarbon Receptor
27 T-Cell Receptor and Co-stimulatory Signaling
28 Apoptosis
29 Quercetin and Nf-kB/ AP-1 Induced Cell Apoptosis
30 BDNF signaling pathway
31 Integrated Pancreatic Cancer Pathway
32 Oncostatin M Signaling Pathway
33 Corticotropin-releasing hormone
34 AGE/RAGE pathway
35 TNF alpha Signaling Pathway
36 B Cell Receptor Signaling Pathway
37 TSLP Signaling Pathway
38 IL17 signaling pathway
39 Neural Crest Differentiation
40 TWEAK Signaling Pathway
41 Leptin signaling pathway
42 RANKL/RANK Signaling Pathway
43 Integrated Breast Cancer Pathway
44 Signalling by NGF
45 IL-1 signaling pathway
46 TCR signaling
47 RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways
48 Interleukin-1 signaling
49 Interleukin-1 processing
50 Apoptosis Modulation and Signaling
51 Folate Metabolism
52 TFs Regulate miRNAs related to cardiac hypertrophy
53 MicroRNAs in cardiomyocyte hypertrophy
54 Vitamin B12 Metabolism
55 Selenium Micronutrient Network
56 Regulation of toll-like receptor signaling pathway
57 Osteopontin Signaling
References
Reference 1 Tolfenamic acid and pancreatic cancer growth, angiogenesis, and Sp protein degradation. J Natl Cancer Inst. 2006 Jun 21;98(12):855-68.
Reference 2 Combination of tolfenamic acid and curcumin induces colon cancer cell growth inhibition through modulating specific transcription factors and reactive oxygen species. Oncotarget. 2016 Jan 19;7(3):3186-200.
Reference 3 Combination of clotam and vincristine enhances anti-proliferative effect in medulloblastoma cells. Gene. 2019 Jul 15;705:67-76.
Reference 4 NF-KappaB inhibition by dimethylaminoparthenolide radiosensitizes non-small-cell lung carcinoma by blocking DNA double-strand break repair. Cell Death Discov. 2018 Feb 7;4:10.
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