9-cis-Retinoic acid

Description

Alitretinoin was introduced in the US for the topical treatment of cutaneous lesions in patients with Kaposi's sarcoma (KS), the most frequent malignancy observed in AIDS patients. It is a derivative of 9-cis-retinoic acid (9- cis-RA) identified as an endogenous hormone in mammalian tissues. Alitretinoin binds to all isoforms of the intracellular retinoid X (RXR) and retinoid A (RAR) receptors thus inducing cell differentiation, increasing cell apoptosis and inhibiting cellular proliferation in experimental models of human cancer. In an international phase III trial in patients with KS, 42% of 82 patients treated with 0.1% gel formulation experienced complete or partial responses cf 7% for controls. Alitretinoin is the first topical therapy for KS and is expected to be a new option to its traditional management.

Chemical Properties

Pale Yellow Solid

Originator

Ligand (US)

Uses

9-cis-Retinoic acid is a vitamin A analog that inhibits cell proliferation and induces cell differentiation. 9-cis-Retinoic acid is an inhibitor of Cox-2 and an activator of RAR α, RAR β, RAR γ and RXR.

Uses

An endogenous retinoic acid isomer, which is capable of binding to both retinoic acid receptors (RAR) and retinoid X receptors (RXR). A biologically active ligand for members of the RAR and RXR subfamilies, implying that it may play a critical role in regulating retinoid-responsive pathways.

Definition

ChEBI: A retinoic acid in which the exocyclic double bonds have 7E,9Z,11E,13E geometry.

Indications

Alitretinoin (Panretin) is a naturally occurring endogenous retinoid that binds to and activates all known retinoid receptors (both RARs and RXRs). It is approved for the topical treatment of cutaneous lesions of Kaposi’s sarcoma. Most patients have local irritation while using alitretinoin gel; however, the irritation rarely necessitates discontinuation of therapy.

brand name

Panretin (Ligand).

Biochem/physiol Actions

Ligand for both the retinoic acid receptor (RAR) and the retinoid X receptor (RXR) that act as transcription factors to regulate the growth and differentiation of normal and malignant cells.

Synthesis

Preparation of isotretinoin EP impurity D (compound of formula I): under the protection of nitrogen, add 2L of ethanol and 100g of all-trans retinoic acid to the reaction flask with stirring, and then increase the temperature to 50-55 , add PdCl289mg. 1.5h after the reaction, the purity of the product was 21% by HPLC. The reaction solution was slowly cooled down to 0~5C, held for 180 min, and filtered; the filtrate was added into another clean reaction flask, and continued to be cooled down to -10~-6C, held for 20 min, and filtered, to obtain the product isotretinoin EP impurity D 12.1g, with a total yield of 12.1%, and a purity of 99.60% by HPLC. Allelvic acid can be obtained from all-trans retinoic acid as raw material in common industrial-grade organic solvents using palladium compound catalysis. The method is easy to operate, low cost, controlled conditions, and convenient for industrial production; after the post-processing step, alevetic acid with a purity of more than 99% can be obtained, and the product yield reaches more than 12%, which has high application value.