Birinapant (also known as TL32711) is a SMAC mimetic antagonist and an inhibitor of IAP (Inhibitor of Apoptosis Protein) family proteins, with antitumor activity in vivo. Birinapant has high binding affinity (nM range) for cIAP1/2 and XIAP. Birinapant (TL32711) caused rapid cIAP1 degradation, caspase activation, PARP cleavage, and NF-κB activation. Birinapant induces cell death as a single agent in TRAIL-insensitive SUM190 (ErbB2-overexpressing) cells and significantly increases potency of TRAIL-induced apoptosis in TRAIL-sensitive SUM149 (triple-negative, EGFR-activated) cells. TL32711 (Birinapant) combined with TNF-α inhibited the growth of a melanoma cell line with acquired resistance to BRAF inhibition to the same extent as in the parental cell line. In addition, Birinapant in combination or as a single agent decreased colony formation and anchorage-independent growth potential of IBC cells. TL32711 is currently in a phase 2 single agent and combination clinical studies in solid tumors.
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
The novel SMAC mimetic birinapant exhibits potent activity against human melanoma cells.
Krepler C, et al. Clin Cancer Res. 2013 Apr 1;19(7):1784-94. PMID: 23403634.
Smac mimetic Birinapant induces apoptosis and enhances TRAIL potency in inflammatory breast cancer cells in an IAP-dependent and TNF-α-independent mechanism.
Allensworth JL, et al. Breast Cancer Res Treat. 2013 Jan;137(2):359-71. PMID: 23225169.
|Related IAP Products|
SM-164 is a potent cell-permeable and bivalent Smac mimetic which bind to a XIAP protein with a Ki value of 0.56 nM, and binds to cIAP-1 and cIAP-2 proteins with Ki values of 0.31 and 1.1 nM, respectively.
LCL161 is an orally bioavailable SMAC mimetic, potently binds to and inhibits multiple IAPs (i.e. XIAP, c-IAP).
BV6 is a small-molecule Smac mimetic, which antagonizes IAP proteins.
GDC-0152 is a potent small-molecule antagonist of inhibitor of apoptosis (IAP) proteins with potential antineoplastic activity.
AT-406 is an orally bioavailable potent IAP (inhibitor of apoptosis protein) of XIAP, cIAP1 and cIAP2 with Ki of 66.4 nM, 1.9 nM and 5.1 nM, respectively.
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