868540-17-4

Posted by freemexy on July 4th, 2019

868540-17-4

PR171 is a novel, orally small-molecule Wnt inhibitor that inhibits TNIK (TRAF2 and NCK-Interacting Kinase). In vitro study has shown that NCM-0846 blocks Wnt signaling and exhibits remarkable anti-tumor and anti-CSC activities. In vivo study has also confirmed that NCB-0846 can inhibit Wnt-driven intestinal tumorigenesis in Apc min/+ mice and the sphere- and tumor-forming activities of colorectal cancer cells. NCB-0846 causes a dose-dependent reduction of the multiplicity and dimensions of tumors that developed in the small intestine. It also significantly suppresses the growth of the PDXs (patient-derived xenografts) established from the two patients in two more clinically relevant mouse models. Therefore, NCM-0846 has the potential to become a useful therapeutic method for tumor treatment.
Carfilzomib is an irreversible proteasome inhibitor and antineoplastic agent.The mechanism of action of carfilzomib is as a Proteasome Inhibitor, Carfilzomib irreversibly binds to and inhibits the chymotrypsin-like activity of the 20S catalytic core subunit of the proteasome, a protease complex responsible for degrading a large variety of cellular proteins. Inhibition of proteasome-mediated proteolysis results in an accumulation of polyubiquinated proteins, which may lead to cell cycle arrest, induction of apoptosis, and inhibition of tumor growth.
Carfilzomib is used in treatment of refractory multiple myeloma. Carfilzomib is associated with a low rate of serum enzyme elevations during treatment and has been implicated to rare instances of clinically apparent, acute liver injury some of which have been fatal.
Carfilzomib is a second-generation, irreversible, peptide epoxyketone class proteasome inhibitor that targets the chymotrypsin-like β5 subunit of the constitutive 20S proteasome (IC50 = 5.2 nM) and the β5i subunit of the immunoproteasome 20Si (LMP7; IC50 = 14 nM) with minimal cross reactivity to other proteases. It can induce cell cycle arrest and apoptosis in human cancer cell lines including multiple myeloma, lymphoma, and various solid tumors (IC50s = 2.4-20 nM).

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