Tretinone

Tretinone, also known by its IUPAC name 4-oxo-4,5,6,7-tetradehydroretinoic acid, is a synthetic analogue of retinoic acid. It is structurally related to tretinoin (all‑trans retinoic acid) but contains a 4-oxo functional group that alters its binding affinity for retinoic acid receptors (RARs). The compound was first synthesized in the late 1970s during efforts to develop retinoid‐based therapeutics with improved potency and reduced cutaneous side effects.

Clinical research on tretinone has focused mainly on dermatological indications. In vitro studies demonstrate that it promotes keratinocyte differentiation and inhibits the formation of comedones, similar to tretinoin. Small‑scale randomized trials have reported modest improvements in mild to moderate acne vulgaris and photoaging when applied topically at concentrations ranging from 0.05 % to 0.10 %. Compared with tretinoin, tretinone appears to induce less erythema and dryness, though data are limited and further large‑scale studies are required to confirm these observations.

The pharmacokinetic profile of tretinone indicates good skin penetration and a half‑life of approximately 24 hours within the epidermis. Systemic absorption is minimal when administered in topical formulations, reducing the risk of systemic retinoid toxicity. Metabolism occurs primarily through cytochrome P450 enzymes in the dermis, yielding inactive hydroxy‑metabolites that are excreted unchanged.

Safety data suggest that tretinone is well tolerated in short‑term studies; common adverse reactions include transient skin irritation, scaling, and increased photosensitivity. Long‑term safety and efficacy remain under investigation, and regulatory approvals for tretinone are limited to specific jurisdictions. Consequently, most dermatologists continue to rely on established retinoids such as tretinoin and adapalene for routine treatment of acne and photoaging.