DIFLUNISAL (PD002374, HUPFGZXOMWLGNK-UHFFFAOYSA-N)

General

Preferred name

DIFLUNISAL

Synonyms

MK-647

Dolobid

Dolobis

Flovacil

Fluniget

Diflusinal

Dolobid, Dolobis, Flovacil, Fluniget,MK-647

NSC-756728

Dolobid 500

P&D ID

PD002374

CAS

22494-42-4

Tags

available

drug

obsolete probe

Approved by

FDA

First approval

1982

Drug indication

Pain

Anti-Inflammatory

Analgesic

Drug Status

approved

investigational

Max Phase

4.0

Structure

PD002374

DIFLUNISAL

obsolete probe

approved

RO5

250.04

HBA

HBD

LOGP

3.04

364

Structure formats

SMILES

O=C(O)c1cc(-c2ccc(F)cc2F)ccc1O

InChI

InChI=1S/C13H8F2O3/c14-8-2-3-9(11(15)6-8)7-1-4-12(16)10(5-7)13(17)18/h1-6,16H,(H,17,18)

InChIkey

HUPFGZXOMWLGNK-UHFFFAOYSA-N

MOL

DIFLUNISAL RDKit 2D 18 19 0 0 0 0 0 0 0 0999 V2000 3.7500 -1.2990 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0000 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7500 1.2990 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5000 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7500 -1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7500 -1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5000 -2.5981 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0000 -2.5981 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7500 -3.8971 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0000 -5.1962 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7500 -6.4952 0.0000 F 0 0 0 0 0 0 0 0 0 0 0 0 -1.5000 -5.1962 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7500 -3.8971 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7500 -3.8971 0.0000 F 0 0 0 0 0 0 0 0 0 0 0 0 -1.5000 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7500 1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7500 1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5000 2.5981 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 2 4 1 0 4 5 2 0 5 6 1 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 2 0 10 11 1 0 10 12 1 0 12 13 2 0 13 14 1 0 6 15 2 0 15 16 1 0 16 17 2 0 17 18 1 0 17 4 1 0 13 7 1 0 M END > <ID> PD002374 > <Name> DIFLUNISAL

Description

(extracted from source data)

TOXICITY Oral LD₅₀ in rat, mouse, and rabbit is 392 mg/kg, 439 mg/kg, and 603 mg/kg, respectively. Symptoms of overdose include drowsiness, nausea, vomiting, diarrhea, hyperventilation, tachycardia, sweating, tinnitus, disorientation, stupor, and coma. As a monotherapy, the smallest dosage capable of causing death was reported as 15 grams.;

Selective COX-2 inhibitors have been associated with increased risk of serious cardiovascular events (e.g. myocardial infarction, stroke) in some patients. Current data is insufficient to assess the cardiovascular risk of diflunisal. Short-term use does not appear to be associated with increased cardiovascular risk (except when used immediately following coronary artery bypass graft (CABG) surgery). Risk of GI toxicity including bleeding, ulceration and perforation. Risk of direct renal injury, including renal papillary necrosis. Severe hepatic reactions, including cholestasis and/or jaundice, have been reported. May cause rash or hypersensitivity syndrome.

DESCRIPTION Diflunisal is a nonsteroidal anti-inflammatory drug (NSAID) (GtoPdb)

Protein targets

7.2

RORC Nuclear receptor ROR-gamma

6.07

SLC22A6 Solute carrier family 22 member 6

CELL-BASED 117.5x

5.72

ALB Albumin

BIOCHEM 1.6x

5.52

TTR Transthyretin

5.38

LMNA Prelamin-A/C

5.3

HIF1A Hypoxia-inducible factor 1-alpha

5.3

CA2 Carbonic anhydrase 2

5.27

CA1 Carbonic anhydrase 1

5.23

ACMSD 2-amino-3-carboxymuconate-6-semialdehyde decarboxylase

4.97

SLC12A5 Solute carrier family 12 member 5

4.75

ALDH1A1 Aldehyde dehydrogenase 1A1

4.7

HSD17B10 3-hydroxyacyl-CoA dehydrogenase type-2

4.68

FBA Fructose-bisphosphate aldolase

4.6

HPGD 15-hydroxyprostaglandin dehydrogenase [NAD(+)]

4.55

KDM4E Lysine-specific demethylase 4E

4.47

DHFR Dihydrofolate reductase inhibitor

4.47

KMT2A,MEN1 Menin/Histone-lysine N-methyltransferase MLL

PTGS1 Prostaglandin G/H synthase 1 inhibitor

PTGS2 Prostaglandin G/H synthase 2 inhibitor

PTGS1,PTGS2 Cyclooxygenase inhibitor

Target pathways

Amyloid fiber formation

R-HSA-977225

TTR

Aspirin ADME

R-HSA-9749641

ALB

Biosynthesis of D-series resolvins

R-HSA-9018676

HPGD

Biosynthesis of DHA-derived SPMs

R-HSA-9018677

PTGS2

Biosynthesis of DPAn-3 SPMs

R-HSA-9025094

PTGS2

Biosynthesis of E-series 18(S)-resolvins

R-HSA-9018896

HPGD

Biosynthesis of electrophilic ω-3 PUFA oxo-derivatives

R-HSA-9027604

PTGS2

Biosynthesis of EPA-derived SPMs

R-HSA-9018679

PTGS2

Biosynthesis of Lipoxins (LX)

R-HSA-2142700

HPGD

Branched-chain amino acid catabolism

R-HSA-70895

HSD17B10

Breakdown of the nuclear lamina

R-HSA-352238

LMNA

Cation-coupled Chloride cotransporters

R-HSA-426117

SLC12A5

Cellular response to hypoxia

R-HSA-1234174

HIF1A

Ciprofloxacin ADME

R-HSA-9793528

ALB

Circadian Clock

R-HSA-400253

HIF1A

COX reactions

R-HSA-140180

PTGS1

Cytoprotection by HMOX1

R-HSA-9707564

ALB

Defective visual phototransduction due to STRA6 loss of function

R-HSA-9918449

TTR

Depolymerization of the Nuclear Lamina

R-HSA-4419969

LMNA

Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models

R-HSA-8862803

LMNA

Erythrocytes take up carbon dioxide and release oxygen

R-HSA-1237044

CA1

CA2

Erythrocytes take up oxygen and release carbon dioxide

R-HSA-1247673

CA1

CA2

Ethanol oxidation

R-HSA-71384

ALDH1A1

Fructose catabolism

R-HSA-70350

ALDH1A1

G1/S-Specific Transcription

R-HSA-69205

DHFR

Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation

R-HSA-8950505

CA1

HDL remodeling

R-HSA-8964058

ALB

Heme biosynthesis

R-HSA-189451

ALB

Heme degradation

R-HSA-189483

ALB

Initiation of Nuclear Envelope (NE) Reformation

R-HSA-2995383

LMNA

Interleukin-10 signaling

R-HSA-6783783

PTGS2

Interleukin-4 and Interleukin-13 signaling

R-HSA-6785807

RORC

PTGS2

HIF1A

Meiotic synapsis

R-HSA-1221632

LMNA

Metabolism of folate and pterines

R-HSA-196757

DHFR

Mitochondrial protein degradation

R-HSA-9837999

HSD17B10

Neddylation

R-HSA-8951664

HIF1A

Neutrophil degranulation

R-HSA-6798695

TTR

Nicotinamide salvaging

R-HSA-197264

PTGS2

Non-integrin membrane-ECM interactions

R-HSA-3000171

TTR

NOTCH1 Intracellular Domain Regulates Transcription

R-HSA-2122947

HIF1A

Nuclear Envelope Breakdown

R-HSA-2980766

LMNA

Nuclear Receptor transcription pathway

R-HSA-383280

RORC

Organic anion transport

R-HSA-561048

SLC22A6

Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha

R-HSA-1234176

HIF1A

Platelet degranulation

R-HSA-114608

ALB

Post-translational protein phosphorylation

R-HSA-8957275

ALB

Prednisone ADME

R-HSA-9757110

ALB

PTK6 Expression

R-HSA-8849473

HIF1A

PTK6 promotes HIF1A stabilization

R-HSA-8857538

HIF1A

RA biosynthesis pathway

R-HSA-5365859

ALDH1A1

Recycling of bile acids and salts

R-HSA-159418

ALB

Regulation of gene expression by Hypoxia-inducible Factor

R-HSA-1234158

HIF1A

Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)

R-HSA-381426

ALB

Retinoid metabolism and transport

R-HSA-975634

TTR

Reversible hydration of carbon dioxide

R-HSA-1475029

CA1

CA2

rRNA processing in the mitochondrion

R-HSA-8868766

HSD17B10

RUNX3 Regulates Immune Response and Cell Migration

R-HSA-8949275

RORC

Scavenging of heme from plasma

R-HSA-2168880

ALB

Signaling by BRAF and RAF1 fusions

R-HSA-6802952

LMNA

STAT3 nuclear events downstream of ALK signaling

R-HSA-9701898

HIF1A

Synthesis of 15-eicosatetraenoic acid derivatives

R-HSA-2142770

PTGS2

Synthesis of Prostaglandins (PG) and Thromboxanes (TX)

R-HSA-2162123

PTGS2

PTGS1

HPGD

Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation

R-HSA-1474151

DHFR

The canonical retinoid cycle in rods (twilight vision)

R-HSA-2453902

TTR

tRNA modification in the mitochondrion

R-HSA-6787450

HSD17B10

tRNA processing in the mitochondrion

R-HSA-6785470

HSD17B10

Tryptophan catabolism

R-HSA-71240

ACMSD

Ub-specific processing proteases

R-HSA-5689880

HIF1A

XBP1(S) activates chaperone genes

R-HSA-381038

LMNA

Zygotic genome activation (ZGA)

R-HSA-9819196

KDM4E

References

2023 Resveratrol Derivatives Inhibit Transthyretin Fibrillization: Structural Insights into the Interactions between Resveratrol Derivatives and Transthyretin.

Yokoyama T, Kusaka K et al. J Med Chem

2023 A preclinical secondary pharmacology resource illuminates target-adverse drug reaction associations of marketed drugs.

Sutherland JJ, Yonchev D et al. Nat Commun

2021 Inhibitory activities of anthraquinone and xanthone derivatives against transthyretin amyloidogenesis.

Kitakami R, Inui K et al. Bioorg Med Chem

2021 Repositioning of the Anthelmintic Drugs Bithionol and Triclabendazole as Transthyretin Amyloidogenesis Inhibitors.

Yokoyama T, Kashihara M et al. J Med Chem

2021 Diflunisal Derivatives as Modulators of ACMS Decarboxylase Targeting the Tryptophan-Kynurenine Pathway.

Yang Y,Borel T et al. J Med Chem

2021 Systematic Development of Peptide Inhibitors Targeting the CXCL12/HMGB1 Interaction.

Sgrignani J, Cecchinato V et al. J Med Chem

2020 The Structural Basis for Nonsteroidal Anti-Inflammatory Drug Inhibition of Human Dihydrofolate Reductase

Duff MR Jr, Gabel SA et al. Journal of Medicinal Chemistry

2020 Calorimetric Studies of Binary and Ternary Molecular Interactions between Transthyretin, Aβ Peptides, and Small-Molecule Chaperones toward an Alternative Strategy for Alzheimer's Disease Drug Discovery.

Cotrina EY, Gimeno A et al. J Med Chem

2020 Transthyretin Amyloidogenesis Inhibitors: From Discovery to Current Developments.

Yokoyama T,Mizuguchi M J Med Chem

2020 The Structural Basis for Nonsteroidal Anti-Inflammatory Drug Inhibition of Human Dihydrofolate Reductase.

Duff MR; Gabel SA et al.

2019 Crown Ethers as Transthyretin Amyloidogenesis Inhibitors.

Yokoyama T, Mizuguchi M. J Med Chem

2018 Enthalpy-Driven Stabilization of Transthyretin by AG10 Mimics a Naturally Occurring Genetic Variant That Protects from Transthyretin Amyloidosis.

Miller M, Pal A et al. J Med Chem

2018 Synthesis and preliminary anti-inflammatory and anti-bacterial evaluation of some diflunisal aza-analogs.

Carta D, Brun P et al. MedChemComm

2017 Peptide Half-Life Extension: Divalent, Small-Molecule Albumin Interactions Direct the Systemic Properties of Glucagon-Like Peptide 1 (GLP-1) Analogues.

Bech EM, Martos-Maldonado MC et al. J Med Chem

2015 Enthalpic Forces Correlate with the Selectivity of Transthyretin-Stabilizing Ligands in Human Plasma.

Iakovleva I, Brannstrom K et al. J. Med. Chem.

2014 Crystal structures of human transthyretin complexed with glabridin.

Yokoyama T, Kosaka Y et al. J. Med. Chem.

2014 Inhibitory activities of propolis and its promising component, caffeic acid phenethyl ester, against amyloidogenesis of human transthyretin.

Yokoyama T, Kosaka Y et al. J. Med. Chem.

2008 New approach to measure protein binding based on a parallel artificial membrane assay and human serum albumin.

Lázaro E; Lowe PJ et al.

2008 In vitro inhibition of salicylic acid derivatives on human cytosolic carbonic anhydrase isozymes I and II.

Bayram E, Senturk M et al. Bioorg. Med. Chem.

2005 Predicting human serum albumin affinity of interleukin-8 (CXCL8) inhibitors by 3D-QSPR approach.

Aureli L, Cruciani G et al. J. Med. Chem.

2000 Nonsteroidal anti-inflammatory drugs efficiently reduce the transport and cytotoxicity of adefovir mediated by the human renal organic anion transporter 1.

Mulato AS; Ho ES et al.

PUBCHEM_BIOASSAY: qHTS Assay for Inhibitors and Activators of N370S glucocerebrosidase as a Potential Chaperone Treatment of Gaucher Disease: Purified N370S Glucocerebrosidase. (Class of assay: confirmatory) [Related pubchem assays: 2101 ] AID 2597

AID 653

AID 1736