Liarozole is an imidazole-containing compound that inhibits the cytochrome P-450-dependent metabolism of all-trans-retinoic acid (RA). Liarozole, a retinoic acid (RA) metabolism-blocking agent (RAMBA) in clinical development, has been granted orphan drug designation for congenital ichthyosis by the European Commission and the U.S. Food and Drug Administration. Later, based on the mixed results from a phase II/III trial of liarozole for the treatment of ichthyosis, Barrier decided to discontinue the development of liarozole. Liarozole displays antitumor activity against androgen-dependent and independent rat prostate carcinomas.A large phase III international study was completed comparing liarozole 300 mg twice daily with cyproterone acetate (CPA) 100 mg twice daily in a total of 321 patients with metastatic prostate cancer in relapse after first-line endocrine therapy. The results indicate that liarozole might be a possible treatment option for prostate cancer (PCA) following failure of first-line endocrine therapy.

Liarozole is an imidazole-containing compound that inhibits the cytochrome P-450-dependent metabolism of all-trans-retinoic acid (RA). Liarozole, a retinoic acid (RA) metabolism-blocking agent (RAMBA) in clinical development, has been granted orphan drug designation for congenital ichthyosis by the European Commission and the U.S. Food and Drug Administration. Later, based on the mixed results from a phase II/III trial of liarozole for the treatment of ichthyosis, Barrier decided to discontinue the development of liarozole. Liarozole displays antitumor activity against androgen-dependent and independent rat prostate carcinomas.A large phase III international study was completed comparing liarozole 300 mg twice daily with cyproterone acetate (CPA) 100 mg twice daily in a total of 321 patients with metastatic prostate cancer in relapse after first-line endocrine therapy. The results indicate that liarozole might be a possible treatment option for prostate cancer (PCA) following failure of first-line endocrine therapy.

Doramapimod (BIRB-796) is a p38 MAPK inhibitor, relatively potent against alpha isoform. Oral doramapimod exerts anti-inflammatory potential in humans in vivo. Doramapimod has entered clinical trials for the treatment of autoimmune diseases.

Apilimod is a small molecule inhibitor of interleukin-12 and interleukin-23 synthesis thereby preventing IL-12/IL-23 mediated immune responses. Apilimod is also observed to inhibit the nuclear accumulation of NF-kappB protein family, and viral infections dependent on phosphatidylinositol-3-phosphate 5-kinase (PIKfyve). Apilimod has been investigated as a potential treatment for a number of autoimmune conditions.

Atizoram (CP-80633) is a phosphodiesterase IV inhibitor with bronchodilatory and antiinflammatory properties. It was in phase II trials with Pfizer in the US for the treatment of asthma, atopic dermatitis and psoriasis. Development of atizoram has been discontinued in the asthma indication and no recent development has been reported for the other indications. CP-80633 inhibits PDE4 isozymes (human lung IC50 = 1.27 uM) in the absence of effects on PDE1, PDE2, PDE3 and PDE5 isozymes (IC50 > 100 uM). It exhibits no significant selectivity for any single cloned PDE4A, B, C or D isoform.

Liarozole is an imidazole-containing compound that inhibits the cytochrome P-450-dependent metabolism of all-trans-retinoic acid (RA). Liarozole, a retinoic acid (RA) metabolism-blocking agent (RAMBA) in clinical development, has been granted orphan drug designation for congenital ichthyosis by the European Commission and the U.S. Food and Drug Administration. Later, based on the mixed results from a phase II/III trial of liarozole for the treatment of ichthyosis, Barrier decided to discontinue the development of liarozole. Liarozole displays antitumor activity against androgen-dependent and independent rat prostate carcinomas.A large phase III international study was completed comparing liarozole 300 mg twice daily with cyproterone acetate (CPA) 100 mg twice daily in a total of 321 patients with metastatic prostate cancer in relapse after first-line endocrine therapy. The results indicate that liarozole might be a possible treatment option for prostate cancer (PCA) following failure of first-line endocrine therapy.

Liarozole is an imidazole-containing compound that inhibits the cytochrome P-450-dependent metabolism of all-trans-retinoic acid (RA). Liarozole, a retinoic acid (RA) metabolism-blocking agent (RAMBA) in clinical development, has been granted orphan drug designation for congenital ichthyosis by the European Commission and the U.S. Food and Drug Administration. Later, based on the mixed results from a phase II/III trial of liarozole for the treatment of ichthyosis, Barrier decided to discontinue the development of liarozole. Liarozole displays antitumor activity against androgen-dependent and independent rat prostate carcinomas.A large phase III international study was completed comparing liarozole 300 mg twice daily with cyproterone acetate (CPA) 100 mg twice daily in a total of 321 patients with metastatic prostate cancer in relapse after first-line endocrine therapy. The results indicate that liarozole might be a possible treatment option for prostate cancer (PCA) following failure of first-line endocrine therapy.

BX 471 is an oral nonpeptide chemokine receptor1 (CCR1) antagonist that was under clinical development with Bayer Healthcare Pharmaceuticals (formerly Bayer Schering Pharma AG and Berlex) for the treatment of various inflammation-related disorders, including endometriosis. The CCR1 antagonist was also thought to have potential application in diagnostic imaging, particularly as an imaging biomarker for the diagnosis of Alzheimer's disease. Berlex initiated the development of the radiolabelled small molecule CCR1 antagonist, BX 471, for a specific diagnostic test for both early detection and for tracking disease progression following the discovery that the CCR1 protein was found in the brains of patients with Alzheimer's disease, and that increased levels of this protein were correlated with advancement of the disease. However, development of the agent for diagnostic imaging appears to have been discontinued. BX 471 was also in development for the treatment of autoimmune diseases, including multiple sclerosis and psoriasis; however, development in these indications, as well as multiple myeloma and endometriosis, also appears to have been discontinued. A phase II study of BX 471 in endometriosis had been completed.

Quaternium-15, a preservative, is one of the most used substances and is added to several cosmetics and other industrial products. Quaternium-15 is a mixture of isomers, where the cis-form is the dominant form and where the trans-form is the minor component present as an impurity. Quaternium-15 can be found under a variety of names, most commonly those of the Dow Chemical Company: Dowicil 200 (cis isomer only), Dowicil 75 and Dowicil 100 (both a mix of cis and trans isomers). The isolated cis-compound is used primarily in cosmetic applications, with a maximum permitted concentration in the EU of 0.2%. DOWICIL 200 preservative (cis form) is used primarily as a preservative in a wide variety of personal-care and cosmetic products. It is designed to provide highly effective broad-spectrum antimicrobial activity, especially in water-based formulations. It is used in both leave-on and rinse-off application such as baby-care products, hair-care products, lotions, powders, and creams. The mixed product (cis- and trans-) is used in a wider range of formulations such as: emulsifiable metal-cutting fluids; latex and emulsion paints; liquid floor polishes and floor waxes; glues and adhesives. Recently, the cis-form has been classified as a CMR substance with the classification toxic to reproduction, category 3. This classification only concerns the cis-isomer:

Quaternium-15, a preservative, is one of the most used substances and is added to several cosmetics and other industrial products. Quaternium-15 is a mixture of isomers, where the cis-form is the dominant form and where the trans-form is the minor component present as an impurity. Quaternium-15 can be found under a variety of names, most commonly those of the Dow Chemical Company: Dowicil 200 (cis isomer only), Dowicil 75 and Dowicil 100 (both a mix of cis and trans isomers). The isolated cis-compound is used primarily in cosmetic applications, with a maximum permitted concentration in the EU of 0.2%. DOWICIL 200 preservative (cis form) is used primarily as a preservative in a wide variety of personal-care and cosmetic products. It is designed to provide highly effective broad-spectrum antimicrobial activity, especially in water-based formulations. It is used in both leave-on and rinse-off application such as baby-care products, hair-care products, lotions, powders, and creams. The mixed product (cis- and trans-) is used in a wider range of formulations such as: emulsifiable metal-cutting fluids; latex and emulsion paints; liquid floor polishes and floor waxes; glues and adhesives. Recently, the cis-form has been classified as a CMR substance with the classification toxic to reproduction, category 3. This classification only concerns the cis-isomer: