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Drugs of interest to pathologists
Veliparib


Minor changes: 24 August 2020

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PubMed Search: Veliparib[TI] free full text[SB]

Y. Albert Yeh, M.D., Ph.D.
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Cite this page: Yeh YA. Veliparib. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/drugsveliparib.html. Accessed October 28th, 2020.
Definition / general
  • A poly (ADP-ribose) polymerase (PARP) inhibitor blocks PARP1 and PARP2, thereby preventing repair of DNA damage
  • Developed by Abbvie
  • Synonym: ABT-888, 912444-00-9, CHEBI:62880, 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide, veliparib
Trade name
  • Veliparib®
Indications
Pathophysiology
  • Base excision repair and homologous recombination mediated double strand breaks system responsible for the repair of damaged DNA (Figure 1, panel A)
  • In cells with BRCA1/2 mutated cells, base excision repair and other DNA repair mechanisms compensate for the nonfunctional homologous recombination (Figure 1, panel B)
  • In cells with nonfunctioning base excision repair because of PARP1 inhibition, at least one copy of BRCA1/2 with functioning homologous recombination can repair the damaged DNA (Figure 1, panel C)
  • In mutated BRCA1/2 cancer cells, PARP inhibitors prevents the base excision repair leading to cell death (Figure 1, panel D)
  • Reference: Mod Pathol 2020;33:944, see diagram below
Diagrams / tables

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Mechanism of PARP1 inhibitor in cancer cells

Clinical information
Uses by pathologists
  • None at this time
Side effects
  • Gastrointestinal: nausea, vomiting
  • Fatigue
  • Myelosuppression (anemia, neutropenia, thrombocytopenia)
  • Secondary leukemia and myelodysplastic syndrome (late serious effects)
  • Reference: Onco Targets Ther 2015;8:1931
Drug administration
  • Drug taken by mouth
Board review style question #1
    Veliparib is a potential therapeutic agent inhibiting which of the following proteins?

  1. BRAF
  2. BRCA1 and BRCA2
  3. PARP1 and PARP2
  4. TP53
Board review answer #1
C. PARP1 and PARP2

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Reference: Veliparib
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