NVP-TNKS656(TNKS-656) is a highly potent, selective, and orally active TNKS2 inhibitor with IC50 of 6 nM; >300 fold selectivity against PARP1 and PARP2. NVP-TNKS656 was identified as an orally active antagonist of Wnt pathway activity in the MMTV-Wnt1 mouse xenograft model. With an enthalpy-driven thermodynamic signature of binding, highly favorable physicochemical properties, and high lipophilic efficiency, NVP-TNKS656 is well suited for further in vivo validation studies.
|Animal models||Athymic female nude mice bearing MMTV-Wnt1 tumors|
|Formulation||4% HCl:10% propylene glycol:20% Solutol HS15:60.5% D5W:0.5% NaOH|
|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.
|Solubility||DMSO 40 mg/mL|
Identification of NVP-TNKS656: the use of structure-efficiency relationships to generate a highly potent, selective, and orally active tankyrase inhibitor.
Shultz MD, et al. J Med Chem. 2013 Aug 22;56(16):6495-511. PMID: 23844574.
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