BEGIN:VCALENDAR VERSION:2.0 PRODID:-//Sabre//Sabre VObject 4.6.1//EN CALSCALE:GREGORIAN BEGIN:VTIMEZONE TZID:Europe/Zurich X-LIC-LOCATION:Europe/Zurich TZURL:http://tzurl.org/zoneinfo/Europe/Zurich BEGIN:DAYLIGHT TZOFFSETFROM:+0100 TZOFFSETTO:+0200 TZNAME:CEST DTSTART:19810329T020000 RRULE:FREQ=YEARLY;BYMONTH=3;BYDAY=-1SU END:DAYLIGHT BEGIN:STANDARD TZOFFSETFROM:+0200 TZOFFSETTO:+0100 TZNAME:CET DTSTART:19961027T030000 RRULE:FREQ=YEARLY;BYMONTH=10;BYDAY=-1SU END:STANDARD END:VTIMEZONE BEGIN:VEVENT UID:news816@chemie.unibas.ch DTSTAMP;TZID=Europe/Zurich:20261027T103817 DTSTART;TZID=Europe/Zurich:20261120T170000 SUMMARY:Development of Next Generation Chemical Strategies in Drug Discover y (Camille & Henry Dreyfus Lecture 2026) DESCRIPTION:Somatic mutations in the small GTPase K-Ras drive roughly 30% o f human cancers\, yet the protein was long considered „undruggable“ un til a covalent strategy targeting the G12C mutant revealed a binding pocke t in the switch-II region\, leading to the approval of sotorasib and adagr asib. These successes have shifted the central challenges in the field: ex tending covalent and non-covalent strategies to the more prevalent G12D an d G12V mutants found in pancreatic and colorectal cancer\, deepening singl e-agent responses\, and overcoming the drug resistance that inevitably eme rges with any targeted therapy. In this lecture I will describe our effort s on each front. First\, I will show that combining the pan-Ras tri-comple x inhibitor daraxonrasib—whose GAP-mimetic activity accelerates GTP hydr olysis—with switch-II pocket inhibitors selective for K-Ras(G12C) or K-R as(G12D) produces synergistic inhibition\, providing a mechanistic rationa le for combination regimens. Second\, I will present a new covalent chemis try that installs a warhead reactive toward the aspartate of K-Ras(G12D)\, extending covalent targeting beyond cysteine residues and inhibiting onco genic signaling in cancer cells. Finally\, I will place this work in the c ontext of two broader chemical biology themes from our lab that inform how such inhibitors are designed and delivered: the discovery that IFITM prot eins govern cellular uptake of chemically linked\, bivalent compounds\, an d a binary pharmacology strategy that restricts mTOR inhibition to brain t issue. Together these findings illustrate how mechanistic combination logi c\, new covalent chemistries\, and uptake-and tissue-informed drug design are converging to widen the therapeutic reach for new medicines.\\r\\n\\r\ \nCamille & Henry Dreyfus LectureshipIn memory of the Dreyfus brothers\, t he Camille and Henry Dreyfus Foundation Inc. has established the Camille & Henry Dreyfus Lectureship at the University of Basel [https://chemie.unib as.ch/de/aktuelles/veranstaltungen/dreyfus-lectureship/]. The annual Lectu reship brings a leading chemist from the United States to the Basel campus to deliver a series of talks\, and to meet with faculty and students in o rder to enhance the relationship between Swiss and U.S. science. X-ALT-DESC:

Somatic mutations in the small GTPase K-Ras drive roughly 30% of human cancers\, yet the protein was long considered „undruggable“ until a covalent strategy targeting the G12C mutant revealed a binding poc ket in the switch-II region\, leading to the approval of sotorasib and ada grasib. These successes have shifted the central challenges in the field: extending covalent and non-covalent strategies to the more prevalent G12D and G12V mutants found in pancreatic and colorectal cancer\, deepening sin gle-agent responses\, and overcoming the drug resistance that inevitably e merges with any targeted therapy. In this lecture I will describe our effo rts on each front. First\, I will show that combining the pan-Ras tri-comp lex inhibitor daraxonrasib—whose GAP-mimetic activity accelerates GTP hy drolysis—with switch-II pocket inhibitors selective for K-Ras(G12C) or K -Ras(G12D) produces synergistic inhibition\, providing a mechanistic ratio nale for combination regimens. Second\, I will present a new covalent chem istry that installs a warhead reactive toward the aspartate of K-Ras(G12D) \, extending covalent targeting beyond cysteine residues and inhibiting on cogenic signaling in cancer cells. Finally\, I will place this work in the context of two broader chemical biology themes from our lab that inform h ow such inhibitors are designed and delivered: the discovery that IFITM pr oteins govern cellular uptake of chemically linked\, bivalent compounds\, and a binary pharmacology strategy that restricts mTOR inhibition to brain tissue. Together these findings illustrate how mechanistic combination lo gic\, new covalent chemistries\, and uptake-and tissue-informed drug desig n are converging to widen the therapeutic reach for new medicines.

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Camille &\; Henry Dreyfus Lectureship
In memor y of the Dreyfus brothers\, the Camille and Henry Dreyfus Foundation Inc. has established the Camille &\; Henry Dreyfu s Lectureship at the University of Basel. The annual Lectureship bring s a leading chemist from the United States to the Basel campus to deliver a series of talks\, and to meet with faculty and students in order to enha nce the relationship between Swiss and U.S. science.

DTEND;TZID=Europe/Zurich:20261120T183000 END:VEVENT END:VCALENDAR