Identification of the Highly Active, Species Cross-Reactive Complex I Inhibitor BAY-179.

Mitochondria are key regulators of energy supply and cell death. Generation of ATP within mitochondria occurs through oxidative phosphorylation (OXPHOS), a process which utilizes the four complexes (complex I-IV) of the electron transport chain and ATP synthase. Certain oncogenic mutations (, LKB1 or mIDH) can further enhance the reliance of cancer cells on OXPHOS for their energetic requirements, rendering cells sensitive to complex I inhibition and highlighting the potential value of complex I as a therapeutic target.

Discovery of Vilaprisan (BAY 1002670): A Highly Potent and Selective Progesterone Receptor Modulator Optimized for Gynecologic Therapies.

Progesterone plays an important role in the female reproductive system. However, there is also evidence that gynecologic disorders/diseases such as uterine fibroids and endometriosis are progesterone-dependent. Steroidal and non-steroidal selective progesterone receptor modulators (SPRMs) have shown potential for the treatment of such diseases.

Preclinical Efficacy of the Novel Monocarboxylate Transporter 1 Inhibitor BAY-8002 and Associated Markers of Resistance.

The lactate transporter /monocarboxylate transporter 1 (MCT1) plays a central role in tumor cell energy homeostasis. In a cell-based screen, we identified a novel class of MCT1 inhibitors, including BAY-8002, which potently suppress bidirectional lactate transport. We investigated the antiproliferative activity of BAY-8002 in a panel of 246 cancer cell lines and show that hematopoietic tumor cells, in particular diffuse large B-cell lymphoma cell lines, and subsets of solid tumor models are particularly sensitive to MCT1 inhibition.

BAY 1002670: a novel, highly potent and selective progesterone receptor modulator for gynaecological therapies.

Study Question: Does the novel progesterone receptor (PR) modulator BAY 1002670, based on its preclinical pharmacological profile, offer a potential novel treatment option for uterine fibroids?

Summary Answer: The newly synthesized BAY1002670 has proved to be a very potent, highly selective PR modulator in all in vitro and in vivo pharmacodynamics assays performed: it exhibits marked efficacy in an innovative humanized fibroid disease model, suggesting BAY 1002670 to be a very promising treatment option for uterine fibroids.

What Is Known Already: PR inhibiting ligands have shown clinical utility in a range of potential indications and applications. Despite the emergence of the first PR antagonist >30 years ago, no agent of this compound class has been authorized in any indication for long-term application.

Pharmacology and clinical use of sex steroid hormone receptor modulators.

Sex steroid receptors are ligand-triggered transcription factors. Oestrogen, progesterone and androgen receptors form, together with the glucocorticoid and mineralocorticoid receptors, a subgroup of the superfamily of nuclear receptors. They share a common mode of action, namely translating a hormone-i.