Tretinoin
[CAS# 302-79-4]

Identification

• Classification: API >> Special medicine >> Dermatology medication
• Name: Tretinoin
• Synonyms: 3,7-Dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8-nonatetraenoic acid; all-trans-Retinoic acid; Vitamin A acid
• Molecular Formula: C₂₀H₂₈O₂
• Molecular Weight: 300.44
• CAS Registry Number: 302-79-4
• EC Number: 206-129-0
• SMILES: CC1=C(C(CCC1)(C)C)/C=C/C(=C/C=C/C(=C/C(=O)O)/C)/C

Properties

• Solubility: insoluble (water), 25 mM (DMSO), 10 mM (ethanol) (Expl.)
• Density: 1.0±0.1 g/mL, Calc.^*
• Melting point: 180-181 °C (Expl.)
• Index of Refraction: 1.556, Calc.^*
• Boiling Point: 462.8±14.0 °C (760 mmHg), Calc.^*
• Flash Point: 350.6±11.0 °C, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07;GHS08 Danger
• Risk Statements: H315-H319-H335-H360
• Safety Statements: P203-P261-P264-P264+P265-P271-P280-P302+P352-P304+P340-P305+P351+P338-P318-P319-P321-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin irritation	Skin Irrit.	2	H315
Acute hazardous to the aquatic environment	Aquatic Acute	1	H400
Reproductive toxicity	Repr.	1B	H360
Chronic hazardous to the aquatic environment	Aquatic Chronic	1	H410
Acute toxicity	Acute Tox.	4	H302
Eye irritation	Eye Irrit.	2	H319
Chronic hazardous to the aquatic environment	Aquatic Chronic	2	H411
Specific target organ toxicity - single exposure	STOT SE	3	H335
Reproductive toxicity	Repr.	1A	H360
Germ cell mutagenicity	Muta.	2	H341
Reproductive toxicity	Repr.	2	H361
Acute toxicity	Acute Tox.	4	H312

Discovery and Applications

Tretinoin, also known as all-trans retinoic acid, is a derivative of vitamin A and is widely recognized for its significant role in dermatology and oncology. It is a highly bioactive compound that has been extensively studied for its therapeutic properties, particularly in the treatment of acne vulgaris, as well as for its potential applications in cancer treatment.

Tretinoin was first introduced in the 1960s and its efficacy in treating acne was identified shortly after its discovery. It was synthesized as part of a broader investigation into retinoids, which are compounds related to vitamin A. These compounds were studied for their ability to influence cellular growth and differentiation. The discovery of tretinoin’s biological effects was groundbreaking, as it was found to regulate the growth and differentiation of skin cells, which made it particularly useful for treating skin conditions like acne.

Tretinoin works by affecting the skin at a cellular level. It acts as a potent agonist of retinoic acid receptors, which regulate gene expression related to cell growth, differentiation, and apoptosis. In acne treatment, tretinoin promotes the shedding of the outer skin layer, prevents the formation of new comedones (skin blockages that lead to acne), and helps clear pores. It also has anti-inflammatory effects that can reduce the redness and swelling associated with acne lesions.

The application of tretinoin in dermatology began with its approval by the U.S. Food and Drug Administration (FDA) in the 1970s for topical treatment of acne. Since then, its use has expanded to include other dermatological conditions, such as photoaging and hyperpigmentation. Tretinoin is commonly used in combination with other therapies to treat more severe forms of acne, and it is found in topical creams, gels, and lotions.

In addition to its role in dermatology, tretinoin has been studied for its anticancer properties. It was first used in the treatment of acute promyelocytic leukemia (APL), a subtype of leukemia characterized by the presence of abnormal promyelocytes. Tretinoin, when administered in high doses, has been shown to induce differentiation of the abnormal promyelocytes into mature white blood cells, helping to restore normal hematopoiesis. This led to its approval by the FDA in the 1990s as a treatment for APL. The drug remains a cornerstone of APL treatment today, often in combination with chemotherapy or other retinoids.

Tretinoin has also been explored for its potential in treating other cancers, including breast and lung cancer, although its clinical use in these areas is less established compared to its role in dermatology and leukemia. The mechanism by which tretinoin influences cancer cells is related to its ability to regulate gene expression, which can alter cell cycle progression and induce differentiation, apoptosis, or inhibit angiogenesis.

In addition to its therapeutic uses, tretinoin is also a subject of ongoing research. Studies continue to explore its effectiveness in various skin disorders, including psoriasis and eczema, as well as its potential benefits in anti-aging treatments. Its ability to increase collagen production and improve skin texture makes it a popular ingredient in many over-the-counter anti-aging skincare products.

Tretinoin is generally well-tolerated when used as prescribed, though it can cause skin irritation, dryness, and peeling, especially during the initial stages of treatment. These side effects are typically temporary and subside as the skin adapts to the compound. It is important for patients using tretinoin to follow their healthcare provider’s instructions to minimize side effects and ensure optimal results.

In summary, tretinoin is a well-established compound with significant applications in both dermatology and oncology. Its discovery revolutionized the treatment of acne and skin aging, while its therapeutic efficacy in the treatment of acute promyelocytic leukemia has made it a vital drug in cancer care. The continued study of tretinoin underscores its value as a therapeutic agent with broad clinical applications.

References

1990. Treatment of first relapse in acute promyelocytic leukaemia with all-trans retinoic acid. Lancet, 336(8728).
DOI: 10.1016/0140-6736(90)93135-c

1990. Human HOX genes are differentially activated by retinoic acid in embryonal carcinoma cells according to their position within the four loci. Cell Differentiation and Development, 31(2).
DOI: 10.1016/0922-3371(90)90015-o

1979. Enhancement of experimental photocarcinogenesis by topical retinoic acid. Cancer Letters, 7(2-3).
DOI: 10.1016/s0304-3835(79)80100-7