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Dulanermin

Dulanermin (recombinant human Apo2L/TRAIL), a pro-apoptotic soluble protein based on naturally occurring Apo2L/TRAIL, is being developed in collaboration with Amgen.

Dulanermin is the first dual PARA that directly activates the extrinsic apoptotic pathway via the pro-apoptotic death receptors DR4 and DR5.^1,8,16,17 Acting independently of p53, a tumor-suppressor protein that is inactivated in many cancers, PARAs that target DR4 and/or DR5 such as dulanermin have the potential to induce the death of tumor cells that may otherwise be resistant to standard chemotherapy agents.¹⁷

Dulanermin may also activate the intrinsic apoptotic pathway through the mitochondrial amplification loop.¹⁷ Binding of dulanermin selectively induces apoptosis in cancer cells while sparing normal cells.¹⁷

1. Dulanermin is engineered to mimic endogenous Apo2L/TRAIL.¹⁵

   

2. Dulanermin is designed to bind to pro-apoptotic cell-surface receptors DR4 and DR5, thus activating the receptors.¹⁵

   

3. Activated DR4/DR5 recruits the cell death-inducing signaling complex (DISC) and initiates the extrinsic apoptotic signaling cascade.^1,15

   

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