BEGIN:VCALENDAR VERSION:2.0 PRODID:-//WARF - ECPv5.16.4//NONSGML v1.0//EN CALSCALE:GREGORIAN METHOD:PUBLISH X-ORIGINAL-URL:https://www.warf.org X-WR-CALDESC:Events for WARF REFRESH-INTERVAL;VALUE=DURATION:PT1H X-Robots-Tag:noindex X-PUBLISHED-TTL:PT1H BEGIN:VTIMEZONE TZID:America/Chicago BEGIN:DAYLIGHT TZOFFSETFROM:-0600 TZOFFSETTO:-0500 TZNAME:CDT DTSTART:20210314T080000 END:DAYLIGHT BEGIN:STANDARD TZOFFSETFROM:-0500 TZOFFSETTO:-0600 TZNAME:CST DTSTART:20211107T070000 END:STANDARD END:VTIMEZONE BEGIN:VEVENT DTSTART;TZID=America/Chicago:20210423T100000 DTEND;TZID=America/Chicago:20210423T110000 DTSTAMP:20230803T063326 CREATED:20210304T184812Z LAST-MODIFIED:20220405T131937Z UID:24585-1619172000-1619175600@www.warf.org SUMMARY:New Strategies to Drug Challenging Targets by Exploiting Covalent Targeting\, Beyond Rule of 5 Bitopic Ligands and Binary Pharmacology DESCRIPTION:The GTP-ase K-Ras represents the most frequently altered oncogene in cancer patients. Directly targeting K-Ras is difficult due to its picomolar affinity for GTP/GDP and the absence of easily identifiable allosteric sites. \nKevan M. Shokat\, a professor of cellular and molecular pharmacology at UCSF\, a professor of chemistry at UC Berkeley and an investigator with the Howard Hughes Medical Institute\, will describe the discovery of small molecules that covalently bind to a common oncogenic mutant\, K-RasG12C. These compounds have served as a blueprint for the development of multiple K-RasG12C drugs currently undergoing clinical investigation. \nMany drug discovery efforts are hampered by the size limit of cell permeable ligands. Shokat will discuss an unusually large (>1700Da) bitopic ligand termed Rapa-Link which inhibits all drug resistant forms of the nutrient sensor kinase\, mTOR. The particular physicochemical properties of this molecule can be exploited to overcome a common challenge in drug discovery termed on target/off tissue toxicity by leveraging a new binary pharmacology platform. \nThis seminar is part of the Pharmaceutical Sciences Seminar Series/WARF Therapeutics Distinguished Lecture in Drug Discovery. To obtain the Webex link\, contact Debra King at Debra.King@wisc.edu. 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