Table 1.
Characterization of PARP inhibitors with preclinical data in hematological malignancies
Name of Inhibitor | Structure | IC50 | In vitro effects | In vivo effects | Stage of Development |
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Talazoparib (BMN673) |
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0.6nM | Combination with DNMTis synergistic toxicity and reduced colony formation. | Combination with DNMTis resulted in increase in overall survival and significant anti-tumor response. | Recruiting/Phase 1 |
Olaparib (Ku-0059436) |
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5nM | Anti-proliferative and apoptotic events in AML cell lines, accumulation of S phase cell cycle arrest. Synergistic anti-leukemic effects in combination with HDACi, WEE1 inhibition, GO. | Increase in overall survival in combination with AZD1775 | Phase 1 Phase 2 |
PJ34 HCl |
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N/A | Dose-dependent decrease in cell viability, induces apoptosis in AML cell lines. | Alleviated hepatomegaly and splenomegaly and reduced level of C1498 cells. | N/A |
Veliparib (ABT 888) |
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5nM | Anti-leukemic activity in combination with DNMTis. Synergistic anti-proliferative effects in combination with TRAIL. Enhances activity of TMZ. | Veliparib combined with Cisplatin achieved significant tumor growth inhibition. | Phase I Active not yet recruiting |
Niraparib (MK-4827) |
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4nM | N/A | N/A | N/A |
Rucaparib (AG-0146991,PF-01367338) |
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1nM | Increased sensitivity in AML cell lines at 0.1–100M. | Significant improvement in overall survival in combination with fluororacil. | N/A |