NVP-TNKS656

NVP-TNKS656 is a highly potent, selective, and orally active TNKS2 inhibitor with IC50 of 6 nM, and is > 300 fold selectivity against PARP1 and PARP2.

Research Areas >> Cancer

TNKS2:6 nM (IC50)

PARP2:32 μM (IC50)

NVP-TNKS656 (30 or 100 mg/kg, p.o.) exhibits good exposure and moderate oral bioavailability of 32% and 53%, respectively. Some slight overproportional increase in oral exposure is observed between 30 and 100 mg/kg with the dose normalized AUC for the 100 mg/kg dose being 2-fold higher than for the 30 mg/kg dose. Mice treated with NVP-TNKS656 (350 mg/kg, p.o.) show good plasma and tumor exposures corresponding to AUC0-24h of 515 and 325 μM·h, respectively[1].

Athymic female nude mice weighing 19-22 g are implanted subcutaneously with a 3×3×3 mm3 tumor fragment from an MMTV-Wnt1 tumor-bearing mouse. Tumors are grown to approximately 250-300 mm3. Individual mice are given a single oral dose of vehicle (n=3) (4% HCl:10% propylene glycol:20% Solutol HS15:60.5% D5W:0.5% NaOH) or TNKS656 at 350 mg/kg (n=18). At 0.5, 1, 2, 4, 8, 16, or 24 h following dosing (n=3/time point), mice are euthanized, and blood is collected via cardiac puncture and processed for plasma. Tumors are excised from mice and frozen at −80°C for PD analysis.

[1]. Shultz MD, et al. Identification of NVP-TNKS656: the use of structure-efficiency relationships to generate a highly potent, selective, and orally active tankyrase inhibitor. J Med Chem. 2013 Aug 22;56(16):6495-511.

Talazoparib | XAV-939 | MK-4827(Niraparib) | Veliparib (ABT-888) | Rucaparib (AG-014699) phosphate | PJ34 HCl | Pamiparib | Rucaparib camsylate | E-7449 | AZD2461 | G007-LK | Iniparib (BSI-201) | NMS-P118 | A-966492 | AG14361