Shenvi Lab
Principal Investigator: Ryan Ashok Shenvi
Institution: Scripps Research Institute (La Jolla, CA)
Primary Subfield: Molecular & Cell Bio
Recruitment Status: Inquire for rotation/fellowship opportunities
Research Focus
Abstract The Galbulimima (GB) alkaloids are derived from the bark of the Galbulimima genus, which features in the traditional medicine and ritual of Papua New Guinea. GB alkaloid content varies markedly among individual trees, and only some bark samples cause hallucination. The number of alkaloids contained in the bark and their general scarcity complicate identification of the biomolecular targets and rigorous pharmacological characterization. Here we describe new chemical platforms for procurement of each Galbulimima alkaloid, the first new biological targets identified in over three decades and preliminary interrogation by pharmacology and structural biology. Viability of the synthetic platform is supported by route that reduce synthetic burden approximately three-fold. The first section of the grant demonstrates gram-scale Class Ia/b GB alkaloid accession by ligand-controlled cross-electrophile coupling (XEC). This strategy allows modular assembly of the carbocyclic (decalin) core with a variety of piperidine side-chains—motifs that define GB alkaloids. Whereas Class Ia targets mAChRs, scaffold rearrangement to Class Ib changes GPCR selectivity to ORs. Preliminary data suggests…
Active NIH Awards
- 5R01AT012075-04: Deconvolution of Galbulimima bark pharmacology through chemical synthesis and target assignment (2026)
- 5R35GM122606-10: Unusual Pharmacophores and New Tools for Cross-Coupling (2026)
- 1R01DA065827-01: Stabilized Salvinorin Analogs (2026)
- 5R35GM122606-09: Unusual Pharmacophores and New Tools for Cross-Coupling (2025)
- 5R01AT012075-03: Deconvolution of Galbulimima bark pharmacology through chemical synthesis and target assignment (2025)
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