Novel Non-Peptidomimetic Prenyl Transferase Inhibitors
Rationale: geranylgeranylation of Ras proteins is a key escape pathway for oncogenic cells treated with farnesyl transferase inhibitors (FTIs). Small molecule antagonists of GGTaseI are therefore promising candidates for fully blocking activation of Ras.Leads: Both UC22 and UC23 are drug-like compounds that are likely to be have good oral bioavalability based on their structures and functional groups.In vitro potency: UC22 and UC23 were assayed for their ability to inhibit GGTAase-I geranylgeranylation of RhoA and KRas4B. IC50s are UC22 (0.5 uM RhoA, 0.9 uM KRas4B) and UC23 (0.3 uM RhoA, 2 uM KRas4B).Specificity: both UC22 and UC23 have been shown to be specific for GGTI versus GGTII and FTICell growth inhibitory potency: UC22 and UC23 were assayed for their ability to inhibit proliferation of human cell lines MDA-MB231 and MiaPaCa2. IC50s are UC22 (50uM in MDA-MB231 and 20 uM MiaPaCa2) and UC23 (10 uM in MDA-MB231 and 8 uM in MiaPaCa2). Cell cycle arrest at the G1 phase was observed in these studies.Target: The molecular target is known and there is SAR and a crystal structure which will aid in further medicinal chemistry.
Patent Number: US8093274B2
Application Number: US2008293993A
Inventor: Tamanoi, Fuyuhiko | Kwon, Ohyun | Watanabe, Masaru | Fiji, Hannah
Priority Date: 22 Mar 2006
Priority Number: US8093274B2
Application Date: 6 Oct 2009
Publication Date: 10 Jan 2012
IPC Current: A61K003144 | A61K003140 | A61P003500 | A61P003502 | C07D020748 | C07D021178
US Class: 514356 | 514423 | 546322 | 548531 | 548542
Assignee Applicant: The Regents of the University of California
Title: Inhibitors of protein prenyltransferases
Usefulness: Inhibitors of protein prenyltransferases
Summary: (I) is useful to inhibit the growth of a cancer cell, where the cancer is pancreatic, leukemia, breast, lung, colon, ovarian, stomach and prostate cancer (claimed).
Novelty: New heterocyclic compounds are protein prenyltransferase inhibitors, useful to inhibit the growth of the cancer (e.g. pancreatic, breast, lung and colon cancer) cells
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癌症/肿瘤
8093274
State Of Development UCLA is seeking commercial partners who are strategically interested in keeping abreast of this work or who may be interested in a strategic collaboration and/or in-licensing for further development of these leads through to an IND. Additional Technologies by these Inventors Tech ID/UC Case 20273/2006-357-0 Related Cases 2006-357-0
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