Mitochondrial Dysfunction & Cell Death Induction

Gam-05 induces multi-layered mitochondrial collapse, a hallmark of irreversible cancer cell death:

Key Functional Readouts

1. Mitochondrial Membrane Potential (MMP):
   1. Significant reduction with mitochondrial-targeted Gam-05 constructs
   2. Stronger effect than non-targeted analogs
2. Cytochrome-c Release:
   1. Triggered selectively by Gam-05
   2. Activates intrinsic apoptotic pathways

• Not observed with classical inhibitors

1. Oxidative Phosphorylation Disruption:
   1. Inhibition of Complex II
   2. Decreased ATP synthesis

• Increased metabolic stress and ROS

1. Oxygen Consumption Rate (OCR):

• 1. Dose-dependent suppression (1–10 µM)
  2. Indicates forced collapse of mitochondrial bioenergetics
  3. 17-AAG shows no mitochondrial effect

Takeaway: Gam-05 directly attacks the metabolic survival axis of cancer cells, a vulnerability increasingly prioritized in oncology drug development.