ABT-888 is a potent, orally bioavailable PARP-1/-2 inhibitor shown to potentiate DNA damaging agents. The ability to potentiate temozolomide (TMZ) and develop a biological marker for PARP inhibition was evaluated in vivo. Veliparib, also known as ABT-888, is a potent inhibitor of PARP-1 and PARP-2, with Ki values of 5.2 nM and 2.9 nM, respectively. It was demonstrated to have good oral bioavailability, to cross the blood-brain barrier well, to have modest antitumor activity alone, and to potentiate temozolomide, platinums, cyclophosphamide, and radiation in syngeneic and xenograft tumor models. Donawho C.K., et al. ABT-888, an orally active poly(ADP-ribose) polymerase inhibitor that potentiates DNA-damaging agents in preclinical tumor models. Clin. Cancer Res. 13: 2728-2737 (2007). A phase 1 clinical study demonstrated that the combination of veliparib with metronomic cyclophosphamide was well tolerated and showed promising activity in a subset of patients with refractory solid tumors and lymphomas and with BRCA mutations. Kummar S., et al. A phase I study of veliparib in combination with metronomic cyclophosphamide in adults with refractory solid tumors and lymphomas. Clin. Cancer Res. 18: 1726-1734 (2012). Pressure-induced myogenic tone was potentiated while endothelium-dependent relaxation was reduced in diabetic mice compared with control mice. PARP-1 inhibitors INO-1001 and veliparib significantly reduced the potentiation of myogenic tone, improved endothelium-dependent relaxation, restored endothelial NO synthase phosphorylation and cGMP, and reduced cleaved PARP-1. PARP-1 inhibitors may be used to overcome diabetic microvascular dysfunction. Choi S.K., et al. Poly(ADP-ribose) polymerase 1 inhibition improves coronary arteriole function in type 2 diabetes mellitus. Hypertension 59: 1060-1068 (2012). This veliparib product is the free base form, whose CAS number is given above. The CAS number of the dihydrochloride salt form is 912445-05-7. Appearance: White to off-white crystalline solid. Purity: 99% (HPLC, TLC) Melting Point: 186-188C Solubility: DMSO, Methanol
Molecular Weight:
244.29
Purity:
99% (HPLC, TLC)
Form:
White to off-white crystalline solid.
CAS Number:
[912444-00-9]
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