Profile of veliparib and its potential in the treatment of solid tumors

Wagner, Lars M.

doi:10.2147/ott.s69935

Cited by 73 publications

(58 citation statements)

References 57 publications

(68 reference statements)

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“…The structure is shown in figure 2. Veliparib inhibits both PARP-1 and PARP-2 with Kis (inhibitory constants) of 5.2 and 2.9nM/L, respectively (Wagner, 2015). As seen with many PARP inhibitors, inhibition by Veliparib is quite selective and pharmacologically relevant concentration of Veliparib doesn't produce substantial effects on other receptors or ion channels.…”

Section: The Drugmentioning

confidence: 99%

“…As seen with many PARP inhibitors, inhibition by Veliparib is quite selective and pharmacologically relevant concentration of Veliparib doesn't produce substantial effects on other receptors or ion channels. Veliparib is used to treat ovarian cancer, oral cancer, basal like breast cancer, pancreatic cancer, prostate cancer (Pahuja et al, 2015;Wagner, 2015).…”

Section: The Drugmentioning

confidence: 99%

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Electrical Pulse-Mediated Veliparib for Effective Treatment of Triple Negative Breast Cancer: An in vitro Model Study

Mittal¹,

Raman²,

Camarillo³

et al. 2017

Int.J.Curr.Res.Aca.Rev.

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Article InfoUse of Poly (ADP-ribose) polymerase (PARP) inhibitors has received major attention as therapeutic agents for the treatment of breast cancers with or without mutations in BRCA1 or BRCA2. Thus, it can be effectively used for triple negative breast cancer (TNBC), which lacks the conventional receptors that many chemo drugs attack. Veliparib, a PARP agent is used as 2 nd line of treatment along with platinum compounds. It is of practical interest to study the efficacy of Veliparib alone as an anticancer drug for TNBC. Towards this, in this research, we studied the efficacy of Veliparib on MDA-MB-231, human triple negative breast cancer cells. A concentration of 330µM was used for this purpose. In addition, to enhance the uptake of Veliparib against the plasma membranes of the cells, electroporation technique is used, which involves the local application of electrical pulses to open pores, which enables easy drug passage across the cell membranes. Thus, the objective of this study is to identify the potential of Veliparib and Electroporation as an alternate combinational therapy for TNBCs. Electrical pulses of high intensity, low duration 1200V/cm, 100μs, 8 pulses and low intensity high duration 500V/cm, 20ms, 8 pulses are used in this study. Cell viabilities were measured immediately, as well as after 24, 48 and 72 hours of treatment. The results indicate cell viabilities of 70% immediately after Veliparib+electrical pulses treatment, compared to 94% with drug only, indicating the potential of the synergy of electrical pulses+Veliparib. The viabilities were lower by 11 to 13 times after 72 hours. This promising treatment is transferrable to clinical practice.

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Section: The Drugmentioning

confidence: 99%

Section: The Drugmentioning

confidence: 99%

Electrical Pulse-Mediated Veliparib for Effective Treatment of Triple Negative Breast Cancer: An in vitro Model Study

Mittal¹,

Raman²,

Camarillo³

et al. 2017

Int.J.Curr.Res.Aca.Rev.

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“…This strategy has facilitated the approval of olaparib (Figure 1) for advanced and relapsed ovarian cancer with germline BRCA mutations. A number of PARP-1 inhibitors have been discovered and several of them are in different stages of clinical trials, including veliparib [11], rucaparib [12] and niraparib ( Figure 1). This brings hope for the treatment of other advanced refractory cancers, such as triple-negative breast, pancreatic, and prostate cancers [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and Biological Evaluation of Novel PARP-1 Inhibitors Based on a 1H-Thieno[3,4-d] Imidazole-4-Carboxamide Scaffold

Wang¹,

Liu²,

Jiang³

et al. 2016

Molecules

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A series of poly(ADP-ribose)polymerase (PARP)-1 inhibitors containing a novel scaffold, the 1H-thieno [3,4-d]imidazole-4-carboxamide moiety, was designed and synthesized. These efforts provided some compounds with relatively good PARP-1 inhibitory activity, and among them, 16l was the most potent one. Cellular evaluations indicated that the anti-proliferative activities of 16g, 16i, 16j and 16l against BRCA-deficient cell lines were similar to that of olaparib, while the cytotoxicities of 16j and 16l toward human normal cells were lower. In addition, ADMET prediction results indicated that these compounds might possess more favorable toxicity and pharmacokinetic properties. This study provides a basis for our further investigation.

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“…About the DNA damage response, a recently developed class of drugs, the poly(ADPribose) polymerase-inhibitors (PARPi), are currently being developed in clinical trials as a targeted treatment, acting on the pathway of DNA repair [13]. PARP-1 is a well-characterized protein in the PARP family: through the base excision repair pathway, it is critical to the repair of single-strand DNA breaks [13][14][15]. The inhibition of PARP conducts to the accumulation of single-strand breaks, resulting in double-strand breaks.…”

Section: Introductionmentioning

confidence: 99%

“…The inhibition of PARP conducts to the accumulation of single-strand breaks, resulting in double-strand breaks. In cells with defective HR (homologous recombination) gene, like the BRCA(Breast Cancer gene)-mutations carriers, PARP inhibition can lead to chromosomal instability, cell cycle arrest and subsequent apoptosis [14]. Recently, similarly to BRCA, also ARID1A mutations have been associated with defects in DNA repair, indicating tumors with such mutations as another possible target of PARPi [15].…”

Section: Introductionmentioning

confidence: 99%