SAR439859, a Novel Selective Estrogen Receptor Degrader (SERD), Demonstrates Effective and Broad Antitumor Activity in Wild-Type and Mutant ER-Positive Breast Cancer Models.

Primary treatment for estrogen receptor-positive (ER+) breast cancer is endocrine therapy. However, substantial evidence indicates a continued role for ER signaling in tumor progression. Selective estrogen receptor degraders (SERD), such as fulvestrant, induce effective ER signaling inhibition, although clinical studies with fulvestrant report insufficient blockade of ER signaling, possibly due to suboptimal pharmaceutical properties.

Discovery of 6-(2,4-Dichlorophenyl)-5-[4-[(3)-1-(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-8,9-dihydro-7-benzo[7]annulene-2-carboxylic acid (SAR439859), a Potent and Selective Estrogen Receptor Degrader (SERD) for the Treatment of Estrogen-Receptor-Positive Breast Cancer.

More than 75% of breast cancers are estrogen receptor alpha (ERα) positive (ER+), and resistance to current hormone therapies occurs in one-third of ER+ patients. Tumor resistance is still ERα-dependent, but mutations usually confer constitutive activation to the hormone receptor, rendering ERα modulator drugs such as tamoxifen and aromatase inhibitors ineffective. Fulvestrant is a potent selective estrogen receptor degrader (SERD), which degrades the ERα receptor in drug-resistant tumors and has been approved for the treatment of hormone-receptor-positive metastatic breast cancer following antiestrogen therapy.

Data on synthesis, ADME and pharmacological properties and early safety pharmacology evaluation of a series of novel NURR1/NOT agonist potentially useful for the treatment of Parkinson's disease.

This article describes the chemical synthesis, ADME and pharmacological properties and early safety pharmacology evaluation of a series of novel Nurr1/NOT agonist. It is meant as a support to an article recently published in Bioorganic and Medicinal chemistry Letters and entitled "Development of a novel NURR1/NOT agonist from hit to lead and candidate for the potential treatment of Parkinson's disease" [1] and presenting the discovery, scope and potential of these new ligands of these nuclear receptors.

Three-step management of a newborn with a giant, highly vascularized, cervical teratoma: a case report.

Background: A giant congenital cervical teratoma is often highly vascularized; thus, in addition to a life-threatening airway occlusion at birth it comprises a high risk for significant and lethal blood loss during resection. In the case presented, an endovascular embolization of the carotid artery that supplied a giant congenital cervical teratoma was done as part of a three-stage treatment soon after birth and contributed to an overall good outcome. Embolization in cases of cervical teratomas was not described previously.

Development of a novel NURR1/NOT agonist from hit to lead and candidate for the potential treatment of Parkinson's disease.

In the course of a programme aimed at identifying Nurr1/NOT agonists for potential treatment of Parkinson's disease, a few hits from high throughput screening were identified and characterized. A combined optimization pointed to a very narrow and stringent structure activity relationship. A comprehensive program of optimization led to a potent and safe candidate drug displaying neuroprotective and anti-inflammatory activity in several in vitro and in vivo models.