BMY 30047: A novel topically active retinoid with low local and systemic toxicity

Journal Article · Tue Jan 01 04:00:00 EST 1991 · Journal of Pharmacology and Experimental Therapeutics; (USA)

OSTI ID:5890709

Nair, X; Quigley, J; Tramposch, K M; Carroll, F I; Lewin, A H; Kiss, I ^[1]

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1. Bristol-Myers Squibb Co., Buffalo, NY (USA)

In the treatment of various dermatological disorders, topically applied retinoids have potential therapeutic use with the advantage of improved localized activity and lower toxicity over systemically administered retinoids. However, most retinoids cause a significant degree of local irritation. In the present study, the ability to produce local activity with low local irritation potential was evaluated with a novel retinoic acid derivative. BMY 30047 (11-cis, 13-cis-12-hydroxymethylretinoic acid delta-lactone) is one of a series of retinoic acid derivatives in which the carboxyl function of the polar end was modified with the aim of achieving reduced local irritation and systemic toxicity while retaining the local therapeutic effect. BMY 30047 was evaluated and compared with all-trans retinoic acid for topical retinoid activity in several preclinical assay systems, including the utricle reduction assay in rhino mice, 12-o-tetradecanoylphorbol 13-acetate ester-stimulated ornithine decarboxylase induction in hairless mice and the UV light-induced photodamaged skin model in hairless mice. BMY 30047 was assessed for retinoid-type side effects by evaluating the skin irritation potential in rabbits after repeated topical application, and hypervitaminosis A-inducing potential in mice after i.p. injection. BMY 30047 demonstrated significant topical retinoid activity in several in vivo models with less skin irritation potential relative to the most used clinical concentrations of all-trans retinoic acid. BMY 30047 also showed very little systemic activity and did not produce any evidence of hypervitaminosis A syndrome at systemic doses 20 times greater than the no-effect dose of all-trans retinoic acid.

• OSTI ID: 5890709
• Journal Information: Journal of Pharmacology and Experimental Therapeutics; (USA), Journal Name: Journal of Pharmacology and Experimental Therapeutics; (USA) Vol. 256:1; ISSN JPETA; ISSN 0022-3565
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
BIOLOGICAL EFFECTS
BODY
CARBON-CARBON LYASES
CARBOXY-LYASES
CARBOXYLIC ACID ESTERS
CARCINOGENS
CHEMOTHERAPY
DECARBOXYLASES
DISEASES
ELECTROMAGNETIC RADIATION
ENZYME INDUCTION
ENZYMES
ESTERS
GENE REGULATION
LYASES
MAMMALS
MICE
ORGANIC COMPOUNDS
ORGANS
PHORBOL ESTERS
RABBITS
RADIATIONS
RETINOIC ACID
RODENTS
SKIN
SKIN DISEASES
THERAPY
TOXICITY
ULTRAVIOLET RADIATION
VERTEBRATES