PARP-2/1-IN-2 (Compound 4a), the enantiomer of Veliparib (HY-10129), is a potent PARP inhibitor with Kis of 2 and 5 nM against PARP-2 and PARP-1, respectively. PARP-2/1-IN-2 has an EC50 of 3 nM in a cell based assay of PARP activity[1].
in vivo
PARP-2/1-IN-2 (Compound 4a) (25 or 50 mg/kg; i.p.) attenuates pain in Cisplatin (HY-17394) and Oxaliplatin (HY-17371)-induced neuropathy in mice[1].
Animal Model:
Male C57BL6J mice, Cisplatin (HY-17394) and Oxaliplatin (HY-17371)-induced painful neuropathy models[1]
Dosage:
25 mg/kg or 50 mg/kg
Administration:
Intraperitoneal injection, two days prior to treatment with Cisplatin or oxaliplatin, with administration continuing by i.p. injection along with the Cisplatin or oxaliplatin regimen (5 days, followed by 5 days of rest, for two weekly cycles)
Result:
Does not attenuate Cisplatin and Oxaliplatin-induced body weight loss. Does not Affect the decline in exploratory behavior associated with Cisplatin and Oxaliplatin Treatment. Attenuates mechanical allodynia in Cisplatin and Oxaliplatin-induced neuropathy. Attenuates thermal hyperalgesia in Cisplatin-induced neuropathy. Attenuates cold hyperalgesia associated with Oxaliplatin-induced neuropathy.
IC 50
PARP2: 2 nM (Ki); PARP1: 5 nM (Ki)
References
[1] Ta LE, et al. A novel and selective poly (ADP-ribose) polymerase inhibitor ameliorates chemotherapy-induced painful neuropathy. PLoS One. 2013;8(1):e54161. DOI:10.1371/journal.pone.0054161
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