864262-97-5Relevant articles and documents
Matrix Metalloproteinase 13 Inhibitors for Modulation of Osteoclastogenesis: Enhancement of Solubility and Stability
Knapinska, Anna M.,Singh, Chandani,Drotleff, Gary,Blanco, Daniela,Chai, Cedric,Schwab, Jason,Herd, Anu,Fields, Gregg B.
supporting information, p. 1133 - 1142 (2021/01/29)
Matrix metalloproteinase 13 (MMP-13) activity has been correlated to breast cancer bone metastasis. It has been proposed that MMP-13 contributes to bone metastasis through the promotion of osteoclastogenesis. To explore the mechanisms of MMP-13 action, we previously described a highly efficacious and selective MMP-13 inhibitor, RF036. Unfortunately, further pursuit of RF036 as a probe of MMP-13 in vitro and in vivo activities was not practical due to the limited solubility and stability of the inhibitor. Our new study has explored replacing the RF036 backbone sulfur atom and terminal methyl group to create inhibitors with more favorable pharmacokinetic properties. One compound, designated inhibitor 3, in which the backbone sulfur and terminal methyl group of RF036 were replaced by nitrogen and oxetane, respectively, had comparable activity, selectivity, and membrane permeability to RF036, while exhibiting greatly enhanced solubility and stability. Inhibitor 3 effectively inhibited MMP-13-mediated osteoclastogenesis but spared collagenolysis, and thus represents a next-generation MMP-13 probe applicable for in vivo studies of breast cancer metastasis.
FERROPTOSIS INHIBITORS–DIARYLAMINE PARA-ACETAMIDES
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Paragraph 01607-01608, (2021/09/11)
Provided are compounds that inhibit ferroptosis activity, or modulate or inhibit a disease associated with ferroptosis dysregulation, such as neuropathy, ischemia reperfusion injury, acute kidney failure and cancer, including corresponding sulfonamides, and pharmaceutically acceptable salts, hydrates and stereoisomers thereof. The compounds are employed in pharmaceutical compositions, and methods of making and use, including treating a person in need thereof with an effective amount of the compound or composition, and detecting a resultant improvement in the person's health or condition.
PYRROLE AND PYRAZOLE COMPOUNDS AND METHODS OF USE THEREOF
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Page/Page column 78, (2020/06/19)
The disclosure relates to anti-cancer compounds derived from nuclear steroid receptor binders, to products containing the same, as well as to methods of their use and preparation. The present disclosure provides compounds having hormone receptor antagonis