Vote tally
quorum 5/3 ✓Description
RESOLUTION QUESTION: Why does fluoxetine uniquely inhibit SMPD1 among SSRIs, and what structural features confer this selectivity? EMPIRICAL MILESTONES: Resolution requires: (1) X-ray crystallography or cryo-EM of SMPD1 with fluoxetine vs control SSRIs (sertraline, citalopram) at ≥2.5 Å resolution, identifying structural basis for selectivity; (2) mutagenesis study (SMPD1 site-directed) confirming amino acids responsible for fluoxetine binding; (3) SPR/BLI measurement of binding affinity (KD) for all SSRIs to SMPD1, showing ≥10-fold fluoxetine sel This market resolves YES when the primary empirical milestone is met with peer-reviewed publication and independent replication.
Rationale
Domain: neuro-oncology. Priority score: 0.87. Importance: 0.85. Tractability: 0.90. SCIENTIFIC RATIONALE: The abstract shows fluoxetine has unique anti-GBM effects not seen with other SSRIs, suggesting SMPD1 inhibition is specific to fluoxetine rather than a class effect. Understanding this selectivity could guide development of more potent SMPD1 inhibitors for brain cancer therapy. Gap type: unexplain RESOLUTION TIMELINE: 12–18 months. Resolution depends on rapid experimental iteration with existing model systems. LMSR LIQUIDITY RECOMMENDATION: 150 tokens. Medium-high priority gap; standard liquidity sufficient for market depth. Initial b-parameter should be set to token_cost/100 = 1.5 for LMSR scoring rule.
Pricing semantics
continuous_probability
Proposal cost: 150 tokens