Gentisic acid

2,5-Dihydroxybenzoic acid is a derivative of benzoic and a powerful inhibitor of fibroblast growth factors.

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> FGFR

Natural Products >> Acids and Aldehydes

Research Areas >> Others

Human Endogenous Metabolite

Fibroblast growth factor

2,5-Dihydroxybenzoic acid (Gentisic acid) is a derivative of benzoic and a minor product of the metabolic break down of aspirin[1]. 2,5-Dihydroxybenzoic acid is also a component of many traditional liquors and herbal remedies, is singled out as a powerful inhibitor of fibroblast growth factors. 2,5-Dihydroxybenzoic acid is used as a lead to identify additional compounds with better inhibitory characteristics generating a new chemical class of fibroblast growth factor inhibitors that includes the agent responsible for alkaptonuria. Through low and high resolution approaches, using representative members of the fibroblast growth factor family and their cell receptors, it is shown that this class of inhibitors may employ two different mechanisms to interfere with the assembly of the signaling complexes that trigger fibroblast growth factor-driven mitogenesis[2].

It is verified from in vivo disease models that this group of inhibitors (e.g., 2,5-Dihydroxybenzoic acid) may be of interest to treat cancer and angiogenesis-dependent diseases[2].

[1]. Levy G, et al. Salicylate accumulation kinetics in man. N Engl J Med. 1972 Aug 31;287(9):430-2.

[2]. IS Fernández, et al. Gentisic acid, a compound associated with plant defense and a metabolite of aspirin, heads a new class of in vivo fibroblast growth factor inhibitors. Journal of Biological Chemistry , 2010, 285(15):11714-29.

3-Methyladenine | Hydrocortisone | Acetylcysteine(N-acetylcysteine) | Retinoic acid | Nintedanib (BIBF 1120) | Infigratinib (BGJ398) | Melatonine | AZD4547 | Dinoprostone | Nicotinamide | Adenosine triphosphate | 4-Acetamidophenol | Prostaglandin E1 | Dehydroepiandrosterone | PD173074

DATA ITEMS CITED :

9

MOLECULAR FORMULA :

C7-H6-O4

MOLECULAR WEIGHT :

154.13

WISWESSER LINE NOTATION :

QVR BQ EQ

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

3 gm/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

4500 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

374 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

380 mg/kg

SEX/DURATION :

female 9 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

642 mg/kg

SEX/DURATION :

female 11 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Specific Developmental Abnormalities - musculoskeletal system

MUTATION DATA

TYPE OF TEST :

DNA inhibition

TEST SYSTEM :

Human Lymphocyte

DOSE/DURATION :

1 mmol/L

REFERENCE :

BCPCA6 Biochemical Pharmacology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.1- 1958- Volume(issue)/page/year: 29,1275,1980 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOHS - National Occupational Hazard Survey (1974) NOHS Hazard Code - M2841 No. of Facilities: 22 (estimated) No. of Industries: 2 No. of Occupations: 2 No. of Employees: 38 (estimated) NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - M2841 No. of Facilities: 39 (estimated) No. of Industries: 2 No. of Occupations: 3 No. of Employees: 259 (estimated) No. of Female Employees: 60 (estimated)