1,721,178 research outputs found
STAT3 direct inhibitors: from MD77 to AC33
No full textSTAT3 (Signal Transducer and Activator of Transcription 3) is a latent cytosolic protein overexpressed in various cancer cell lines which was found to participate in oncogenesis by stimulating cell proliferation and preventing apoptosis [1]. Furthermore, previous studies have shown that blocking constitutively activated STAT3 signaling leads to tumor cell apoptosis, with minimal effect on normal cells [2,3]. This work aims at the synthesis, the structural analysis and the biological evaluation of novel potential antitumor agents, able to inhibit STAT3 protein-protein interaction, starting from MD77 previously identified by our research group [4,5]. Among them, AC33 was selected for further investigations since the AlphaScreen-based assay highlighted its ability to disrupt the STAT3 dimerization, with high selectivity over STAT1 and Grb2. These data induced us to modulate its pharmacokinetic and pharmacodynamic properties. The interesting results obtained will be presented.
This work was supported by a PRIN2010 Grant from MIUR, Italy.
References:
[1] H. Yu, R. Jove, Nat Rev Cancer, 2004, 4, 97-105.
[2] R. Buettner, L.B. Mora, R. Jove, Clin Cancer Res, 2002, 8(4), 945-954.
[3] T. Bowman, R. Garcia, J. Turkson, R. Jove, Oncogene, 2000, 19, 2474-2488.
[4] D-S. Shin, D. Masciocchi, A. Gelain, S. Villa, D. Barlocco, F. Meneghetti, A. Pedretti, Y-M Han, D. C. Han, B.M. Kwon, L. Legnani, L. Toma, Med. Chem. Comm., 2010, 1, 156-164.
[5] D. Masciocchi, S. Villa, F. Meneghetti, A. Pedretti, D. Barlocco, L. Legnani, L. Toma, B. M. Kwon, S. Nakano, A. Asai, A. Gelain, Med. Chem. Comm., 2012, 3, 592-599
Pramlintide (Amylin)
No full textPramlintide is a human amylin analog, under development by Amylin (originally in collaboration with Johnson & Johnson), as an adjunct with insulin for the potential prevention of complications of type I diabetes, and as a single agent for type II diabetes [279804], [295121], [305454]. In December 2000, Amylin submitted a US NDA seeking approval to market pramlintide as an adjunctive therapy for type 1 and 2 diabetics using insulin [392527]; the application was accepted for review by the FDA in January 2001 [396938], and was scheduled for review by the Endocrinologic and Metabolic Drugs Advisory Committee on July 26 2001 [408924]. In May 2001, Amylin submitted an MAA for pramlintide to the EMEA [411323] and in October 2001, Amylin received an approvable letter from the FDA for both Type I and insulin-using Type II diabetes; however, at this time, discussions with the FDA were ongoing regarding additional clinical work that was required before the NDA would be approved [425570]
LAF-237 (Novartis)
No full textNovartis is developing LAF-237, one of a series of orally active dipeptidylpeptidase IV inhibitors, as a potential once daily therapeutic agent for type 2 diabetes. Phase III trials began in the first quarter of 2004
Muraglitazar Bristol-Myers Squibb/Merck
Full text linkA review. Bristol-Myers Squibb and Merck & Co are co-developing muraglitazar, a dual peroxisome proliferator-activated receptor-alpha/gamma agonist, for the potential treatment of type 2 diabetes and other metabolic disorders. In Nov. 2004, approval was anticipated as early as mid-2005
Some aspects of pharmaceutical research in Italian universities. Participants, topics, financing, and intellectual property
No full textA review. The article reviews several aspects of the Italian academic research in medicinal chem. Attention is given to the actors, their funding, their fields of interest and their results, including practical applications
CLX-0901 Calyx Therapeutics
No full textCalyx Therapeutics is developing the insulin sensitizer, CLX-0901, as an antidiabetic agent. CLX-0901 is the synthetic analog of CLX-0900 which was originally isolated from a plant source. Phase I and toxicological studies indicate that the compound is safe and well tolerated [363764]. As of March 2001, phase II studies had commenced [402737]. Other antidiabetics being investigated by Calyx include CLX-0301, CLX-0921, CLX-0940, CLX-0100 and CLX-0101
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