Mechanistic Validation
3. Validation of Selective Target Engagement
Cytosolic Hsp Sparing
Critical De-Risking Data
Akt degradation
Unchanged
Chk1 degradation
Unchanged
Heat shock response
Not induced
Gam-05
Conclusion: Gam-05 does not inhibit cytosolic Hsp, confirming true compartmental selectivity.
🔬 Sensitive Signaling Readout: Src Phosphorylation
01
Src kinase is highly dependent on cytosolic Hsp for stability.
02
Even subtle cytosolic Hsp inhibition rapidly alters p-Src levels.
03
Gam-05 shows no disruption of Src phosphorylation, confirming absence of off-target effects.
This level of mechanistic validation is uncommon at Phase I entry and significantly reduces class-associated risk.