A5034773596- PARP inhibition in cancer therapy
- Phytochemicals and Medicinal Plants
- Toxin Mechanisms and Immunotoxins
- DNA Repair Mechanisms
- Health Systems, Economic Evaluations, Quality of Life
- Biosimilars and Bioanalytical Methods
- CRISPR and Genetic Engineering
- Economic and Financial Impacts of Cancer
- Integrated Circuits and Semiconductor Failure Analysis
- Cardiac electrophysiology and arrhythmias
- Advanced Electron Microscopy Techniques and Applications
AstraZeneca (United Kingdom)
2021-2023
Abstract Purpose: We hypothesized that inhibition and trapping of PARP1 alone would be sufficient to achieve antitumor activity. In particular, we aimed selectivity over PARP2, which has been shown play a role in the survival hematopoietic/stem progenitor cells animal models. developed AZD5305 with aim achieving improved clinical efficacy wider therapeutic window. This next-generation PARP inhibitor (PARPi) could provide paradigm shift outcomes achieved by first-generation PARPi,...
Abstract Purpose: We evaluated the properties and activity of AZD9574, a blood–brain barrier (BBB) penetrant selective inhibitor PARP1, assessed its efficacy safety alone in combination with temozolomide (TMZ) preclinical models. Experimental Design: AZD9574 was interrogated vitro for selectivity, PARylation inhibition, PARP-DNA trapping, ability to cross BBB, potential inhibit cancer cell proliferation. In vivo determined using subcutaneous as well intracranial mouse xenograft Mouse, rat,...
Abstract The Poly (ADP-ribose) polymerase (PARP) family has numerous essential functions in cellular processes such as transcription, chromatin remodelling, DNA damage response and repair well apoptosis. PARP inhibition blocks base excision results conversion of SSBs to double-strand break (DSBs). DSBs are the most deleterious form that can be generated by exogenous damaging agents or endogenous replication stress. repaired homologous recombination (HRR) non-homologous end joining (NHEJ)....
PARP inhibitors (PARPi) are currently indicated for the treatment of ovarian, breast, pancreatic, and prostate cancers harboring mutations in tumor suppressor genes BRCA1 or BRCA2. In case ovarian cancers, their classification as homologous recombination repair (HRR) deficient (HRD) mutated also makes PARPi an available option beyond BRCA2 mutational status. However, identification most relevant genetic alterations driving HRD phenotype has proven difficult recent data have shown that other...
Abstract Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) are currently indicated for the treatment of ovarian, breast, pancreatic and prostate cancers harbouring mutations in tumour suppressor genes BRCA1 or BRCA2 . In case ovarian cancers, their classification as homologous recombination repair (HRR) deficient (HRD) mutated (HRRm) also makes PARPi an available option beyond mutational status. However, identification most relevant genetic alterations driving HRD phenotype has proven...
<p>Supplementary methods, figures, tables</p>
<div>AbstractPurpose:<p>We evaluated the properties and activity of AZD9574, a blood–brain barrier (BBB) penetrant selective inhibitor PARP1, assessed its efficacy safety alone in combination with temozolomide (TMZ) preclinical models.</p>Experimental Design:<p>AZD9574 was interrogated <i>in vitro</i> for selectivity, PARylation inhibition, PARP-DNA trapping, ability to cross BBB, potential inhibit cancer cell proliferation. <i>In vivo</i>...
<p>Supplementary methods, figures, tables</p>
<div>AbstractPurpose:<p>We evaluated the properties and activity of AZD9574, a blood–brain barrier (BBB) penetrant selective inhibitor PARP1, assessed its efficacy safety alone in combination with temozolomide (TMZ) preclinical models.</p>Experimental Design:<p>AZD9574 was interrogated <i>in vitro</i> for selectivity, PARylation inhibition, PARP-DNA trapping, ability to cross BBB, potential inhibit cancer cell proliferation. <i>In vivo</i>...
Abstract The Poly (ADP-ribose) polymerase (PARP) family has numerous essential functions in cellular processes such as transcription, chromatin remodelling, DNA damage response and repair well apoptosis. PARP inhibition blocks base excision results conversion of SSBs to double-strand break (DSBs), the most deleterious form damage. DSBs can be repaired by homologous recombination (HRR) or non-homologous end joining (NHEJ). physiological importance HRR is underscored observation genomic...
Supplementary Figure from Preclinical Characterization of AZD5305, A Next-Generation, Highly Selective PARP1 Inhibitor and Trapper
Supplementary Data from Preclinical Characterization of AZD5305, A Next-Generation, Highly Selective PARP1 Inhibitor and Trapper
Supplementary Data from Preclinical Characterization of AZD5305, A Next-Generation, Highly Selective PARP1 Inhibitor and Trapper
Supplementary Figure from Preclinical Characterization of AZD5305, A Next-Generation, Highly Selective PARP1 Inhibitor and Trapper
Supplementary Figure from Preclinical Characterization of AZD5305, A Next-Generation, Highly Selective PARP1 Inhibitor and Trapper
Supplementary Figure from Preclinical Characterization of AZD5305, A Next-Generation, Highly Selective PARP1 Inhibitor and Trapper
Supplementary Figure from Preclinical Characterization of AZD5305, A Next-Generation, Highly Selective PARP1 Inhibitor and Trapper
Supplementary Figure from Preclinical Characterization of AZD5305, A Next-Generation, Highly Selective PARP1 Inhibitor and Trapper
Supplementary Figure from Preclinical Characterization of AZD5305, A Next-Generation, Highly Selective PARP1 Inhibitor and Trapper
Supplementary Figure from Preclinical Characterization of AZD5305, A Next-Generation, Highly Selective PARP1 Inhibitor and Trapper
<div>AbstractPurpose:<p>We hypothesized that inhibition and trapping of PARP1 alone would be sufficient to achieve antitumor activity. In particular, we aimed selectivity over PARP2, which has been shown play a role in the survival hematopoietic/stem progenitor cells animal models. We developed AZD5305 with aim achieving improved clinical efficacy wider therapeutic window. This next-generation PARP inhibitor (PARPi) could provide paradigm shift outcomes achieved by...
<div>AbstractPurpose:<p>We hypothesized that inhibition and trapping of PARP1 alone would be sufficient to achieve antitumor activity. In particular, we aimed selectivity over PARP2, which has been shown play a role in the survival hematopoietic/stem progenitor cells animal models. We developed AZD5305 with aim achieving improved clinical efficacy wider therapeutic window. This next-generation PARP inhibitor (PARPi) could provide paradigm shift outcomes achieved by...
Supplementary Figure from Preclinical Characterization of AZD5305, A Next-Generation, Highly Selective PARP1 Inhibitor and Trapper
Supplementary Figure from Preclinical Characterization of AZD5305, A Next-Generation, Highly Selective PARP1 Inhibitor and Trapper
Supplementary Figure from Preclinical Characterization of AZD5305, A Next-Generation, Highly Selective PARP1 Inhibitor and Trapper