Diflunisal

Summary

Diflunisal (CHEMBL898) is an approved small-molecule non-steroidal anti-inflammatory drug (ATC N02BA11) targeting DHFR; indicated across 6 conditions including rheumatoid arthritis and osteoarthritis.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N02BA11
• Targets: 1 (DHFR)
• Indications: 6 conditions
• Clinical trials: 5
• Chemistry: 250.2 Da · C13H8F2O3

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL898
Name	Diflunisal
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	3059
ChEBI	CHEBI:39669
ATC	N02BA11
Molecular formula	C13H8F2O3
Molecular weight	250.2
InChIKey	HUPFGZXOMWLGNK-UHFFFAOYSA-N

SMILES: C1=CC(=C(C=C1C2=C(C=C(C=C2)F)F)C(=O)O)O

IUPAC name: 5-(2,4-difluorophenyl)-2-hydroxybenzoic acid

ChEBI definition: An organofluorine compound comprising salicylic acid having a 2,4-difluorophenyl group at the 5-position.

Pharmacological roles (ChEBI): non-steroidal anti-inflammatory drug, non-narcotic analgesic.

Also known as: Diflunisal, Dolobid, Dolobid 500, NSC-756728, SID11112675, SID26746997, SID855794, diflunisal, DIFLUNISAL, SID124882514, SID144204149, SID170464956

Parent form; salt/anhydrous children: CHEMBL4745456

Patent coverage: 14,076 distinct patent families (54,786 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 54,539 (100%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
DHFR	dihydrofolate reductase	Inhibition	4.47	69.8%	P00374

Broader ChEMBL bioactivity targets: 19 (assay-derived). Sample: Lysine-specific demethylase 4E, Ubiquitin carboxyl-terminal hydrolase 2, Nuclear receptor ROR-gamma, Fructose-bisphosphate aldolase, Prelamin-A/C, 15-hydroxyprostaglandin dehydrogenase [NAD(+)], Solute carrier family 22 member 6, Dihydrofolate reductase, Carbonic anhydrase 2, Menin/Histone-lysine N-methyltransferase MLL, High mobility group protein B1, Carbonic anhydrase 1, Transthyretin, Albumin, Stromal cell-derived factor 1, Aldehyde dehydrogenase 1A1, 2-amino-3-carboxymuconate-6-semialdehyde decarboxylase, 3-hydroxyacyl-CoA dehydrogenase type-2, Hypoxia-inducible factor 1-alpha.

Bioactivity

ChEMBL activities: 28 potent at pChembl ≥ 5 of 44 total. Top 100 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
P51450	7.2	Potency	63.1	nM	CHEMBL_ACT_4794863
TTR	7.12	Kd	75	nM	CHEMBL_ACT_22795683
TTR	6.39	Kd	407	nM	CHEMBL_ACT_18557075
TTR	6.24	Kd	580	nM	CHEMBL_ACT_15670991
CXCL12	6.1	Kd	800	nM	CHEMBL_ACT_29087349
SLC22A6	6.07	IC50	850	nM	CHEMBL_ACT_11000886
ALB	5.91	Kd	1230	nM	CHEMBL_ACT_2158024
TTR	5.89	Kd	1300	nM	CHEMBL_ACT_23263057
TTR	5.85	Kd	1400	nM	CHEMBL_ACT_25666927
TTR	5.68	Ki	2100	nM	CHEMBL_ACT_25666885
LMNA	5.65	Potency	2239	nM	CHEMBL_ACT_3639858
ACMSD	5.59	Ki	2560	nM	CHEMBL_ACT_22992418
TTR	5.57	Kd	2700	nM	CHEMBL_ACT_19263636
CA2	5.57	IC50	2700	nM	CHEMBL_ACT_2259039
ALB	5.52	Kd	3000	nM	CHEMBL_ACT_18086456
CA1	5.47	IC50	3380	nM	CHEMBL_ACT_2259030
TTR	5.46	IC50	3500	nM	CHEMBL_ACT_23263029
HIF1A	5.3	Potency	5012	nM	CHEMBL_ACT_4117744
HIF1A	5.3	Potency	5012	nM	CHEMBL_ACT_4519795
TTR	5.25	EC50	5600	nM	CHEMBL_ACT_15121057
TTR	5.25	Kd	5600	nM	CHEMBL_ACT_22795688
TTR	5.2	IC50	6300	nM	CHEMBL_ACT_13960287
USP2	5.2	Potency	6310	nM	CHEMBL_ACT_4739786
TTR	5.18	IC50	6600	nM	CHEMBL_ACT_23169688
LMNA	5.1	Potency	7943	nM	CHEMBL_ACT_3663543
CA1	5.07	Ki	8450	nM	CHEMBL_ACT_2259052
ALDH1A1	5.05	Potency	8912	nM	CHEMBL_ACT_4170437
CA2	5.03	Ki	9370	nM	CHEMBL_ACT_2259059

Target pathways

Aggregated over 1 target gene(s): DHFR.

Top Reactome pathways

3 total, by targets touching each:

Pathway	Targets	Genes
Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation	1	DHFR
Metabolism of folate and pterines	1	DHFR
G1/S-Specific Transcription	1	DHFR

Dominant GO biological processes

GO term	Targets
tetrahydrobiopterin biosynthetic process	1
one-carbon metabolic process	1
negative regulation of translation	1
axon regeneration	1
response to methotrexate	1
dihydrofolate metabolic process	1
tetrahydrofolate metabolic process	1
tetrahydrofolate biosynthetic process	1
folic acid metabolic process	1
regulation of removal of superoxide radicals	1

Indications & clinical

Indications

2 approved indications. FDA phase 4, plus an anticancer drug’s labelled cancer uses (which ChEMBL often logs at phase 3).

Indication	Phase	MONDO	EFO
rheumatoid arthritis	4	MONDO:0008383	EFO:0000685
osteoarthritis	4	MONDO:0005178	MONDO:0005178

2 diseases in clinical trials (phase 1–3, investigational — not approved indications). Highest ChEMBL trial phase per disease; a non-cancer approved use is occasionally logged at phase 3 here.

Disease (in trials)	Phase	MONDO	EFO
familial amyloid neuropathy	2	MONDO:0007100	EFO:0004129
type 2 diabetes mellitus	2	MONDO:0005148	MONDO:0005148

2 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 5.

Phase distribution

Phase	Trials
PHASE4	1
PHASE2/PHASE3	1
PHASE2	1
PHASE1	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01676363	PHASE4	TERMINATED	Pilot Study of Diflunisal in HIV-infected Adults
NCT00294671	PHASE2/PHASE3	COMPLETED	The Effect of Diflunisal on Familial Amyloidosis
NCT00506298	PHASE2	COMPLETED	Study of CRx-401 on Glucose Levels in Subjects With Type II Diabetes
NCT04113668	PHASE1	COMPLETED	The Effects Diflunisal on the Levels of BMS-986165 in Healthy Participants
NCT01432587	Not specified	COMPLETED	The Effect of Diflunisal on Familial Transthyretin Amyloidosis

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

22 molecules share ≥1 primary target. Top 22 by shared-target count:

Molecule	Source	Status	Shared targets
LEUCOVORIN	ChEMBL + PubChem	Phase 4 (approved)	DHFR
METHOTREXATE	ChEMBL + PubChem	Phase 4 (approved)	DHFR
PEMETREXED	ChEMBL + PubChem	Phase 4 (approved)	DHFR
GENTAMICIN	ChEMBL	Phase 4 (approved)	DHFR
MEFENAMIC ACID	ChEMBL	Phase 4 (approved)	DHFR
PRALATREXATE	ChEMBL	Phase 4 (approved)	DHFR
PYRIMETHAMINE	ChEMBL	Phase 4 (approved)	DHFR
RALTITREXED	ChEMBL	Phase 4 (approved)	DHFR
SULFACETAMIDE	ChEMBL	Phase 4 (approved)	DHFR
SULFADIAZINE	ChEMBL	Phase 4 (approved)	DHFR
TERIFLUNOMIDE	ChEMBL	Phase 4 (approved)	DHFR
TRIMETHOPRIM	ChEMBL	Phase 4 (approved)	DHFR
TRIMETREXATE	ChEMBL	Phase 4 (approved)	DHFR
ICLAPRIM	ChEMBL	Phase 3	DHFR
AMINOPTERIN	ChEMBL	Phase 2	DHFR
BREQUINAR	ChEMBL	Phase 2	DHFR
CYCLOGUANIL	ChEMBL	Phase 2	DHFR
DIAVERIDINE	ChEMBL	Phase 2	DHFR
EDATREXATE	ChEMBL	Phase 2	DHFR
EPIROPRIM	ChEMBL	Phase 2	DHFR
PIRITREXIM	ChEMBL	Phase 2	DHFR
Folic Acid	PubChem	Approved	DHFR