Drug Monographs: Olaratumab and Rucaparib

Solimando, Dominic A.; Waddell, J. Aubrey

doi:10.1310/hpj5203-258

Cited by 3 publications

(3 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Poly (ADP-ribose) polymerase 1 (PARP1) is increasingly attractive as an anticancer therapeutic target in both preclinical studies and clinical trials. Many PARP1 inhibitors have been approved for treatment of human malignancies or under clinical investigation, such as olaparib (AZD2281), veliparib (ABT-888), and rucaparib (AG-014699, PF-01367338), for treatment of ovarian cancer, breast cancer, prostate cancer, pancreatic cancer, and unspecified solid tumors [ 1 , 2 , 3 ]. PARP1 has an essential role in cell proliferation, survival, and death, due to its effects on regulation of multiple biological processes [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

PARP1 in Carcinomas and PARP1 Inhibitors as Antineoplastic Drugs

Wang

Liang

et al. 2017

IJMS

View full text Add to dashboard Cite

Poly (ADP-ribose) polymerase 1 (PARP1), the best-studied isoform of the nuclear enzyme PARP family, plays a pivotal role in cellular biological processes, such as DNA repair, gene transcription, and so on. PARP1 has been found to be overexpressed in various carcinomas. These all indicate the clinical potential of PARP1 as a therapeutic target of human malignancies. Additionally, multiple preclinical research studies and clinical trials demonstrate that inhibition of PARP1 can repress tumor growth and metastasis. Up until now, PARP1 inhibitors are clinically used not only for monotherapy to suppress various tumors, but also for adjuvant therapy, to maintain or enhance therapeutic effects of mature antineoplastic drugs, as well as protect patients from chemotherapy and surgery-induced injury. To supply a framework for understanding recent research progress of PARP1 in carcinomas, we review the structure, expression, functions, and mechanisms of PARP1, and summarize the clinically mature PARP1-related anticancer agents, to provide some ideas for the development of other promising PARP1 inhibitors in antineoplastic therapy.

show abstract

Section: Introductionmentioning

confidence: 99%

PARP1 in Carcinomas and PARP1 Inhibitors as Antineoplastic Drugs

Wang

Liang

et al. 2017

IJMS

View full text Add to dashboard Cite

show abstract

“…The catalytic part contains WGR (tryptophan, glycine, and arginine rich) domain, helical domain (HD), and ADP-ribosyl transferase (ART) domain rucaparib, and veliparib are already approved for the treatment of certain cancers. [34][35][36] Some PARP inhibitors and their clinical status are described in Table 2. [37][38][39][40][41][42] BRCA deficient cancer cells which lack homologous recombination are sensitive towards PARP-1 inhibitors due to PARP-1 involvement in DNA damage detection and repair.…”

Section: Role Of Parp-1 In Cancermentioning

confidence: 99%

“…We also found excessive expression of PARP‐1 in HeLa cells (cervical cancer), A549 cells, H1299 cells (lung cancer) and HCT116 cells (colon cancer) (unpublished data). PARP‐1 inhibitors like olaparib, rucaparib, and veliparib are already approved for the treatment of certain cancers 34–36 . Some PARP inhibitors and their clinical status are described in Table 2 37–42 .…”

Section: Role Of Parp‐1 In Different Biological Processesmentioning

confidence: 99%

An assessment of poly (ADP‐ribose) polymerase‐1 role in normal and cancer cells

et al. 2020

View full text Add to dashboard Cite

Poly (ADP-ribose) polymerase (PARP) is a superfamily of 18 proteins characterized by the PARP homology domain, the catalytic domain. This catalytic domain helps in the ADP-ribosylation of various acceptor proteins using nicotinamide adenine dinucleotide (NAD+) as a donor for ADP-ribose. PARP-1 and PARP-2 carry out 80% of poly-ADP-ribosylation of cellular protein. Hence, their combined knockout results in embryonic lethality of mice. PARP-1 consists of three major domains, namely, DNA binding domain, automodification domain, and a catalytic domain. These domains further consist of subdomains and motifs, which helps PARP-1 in a diverse function. PARP-1 is mainly involved in DNA damage detection and repair, but emerging evidence suggests its role in many other functions such as DNA synthesis, replication, apoptosis, necrosis, and cancer progression. Herein, we review the current state of the PARP-1 role in DNA damage repair and other biological processes including epithelial to mesenchymal transition (EMT). We have also observed the role of PARP-1 in modulating EMT regulators like E-cadherin, Vimentin, Claudin-1, Snail, Smad-4, Twist-1, and β-catenin. Here, we have also attempted to relate the role of PARP-1 in EMT of cancer cells.

show abstract

QSAR Model Generation of Phthalazinones as Poly (ADP-Ribose) Polymerase Inhibitors by the Genetic Algorithm and Multiple Linear Regression (GA-MLR) Method: A Ligand-Based Approach for Cancer Drug Design

Ambrose¹,

Afees²,

Kalu³

et al. 2018

J Proteomics Bioinform

View full text Add to dashboard Cite

Poly (ADP-ribose) polymerase-1 (PARP-1), an enzyme known for catalyzing the attachment (covalently) of polymers of ADP-ribose moieties on itself and its target proteins, has been reported in recent study to regulate gene expression in prostate cancer. BRCA mutations are associated in the sensitivity of PARP inhibitors. The present study aimed to develop a Quantitative Structure-Activity Relationship (QSAR) model with Phthalazinones, inhibitors of PARP-1. Phthalazinones were divided into training and test sets to build the QSAR model. Among the several topological, constitutional, geometrical, electronic and hybrid descriptors generated as inputs to the model, three variables were selected by adopting the genetic algorithm subset selection method (GA). The correctness of the proposed model was accounted for by using the following evaluation techniques: Y-randomization, Validation of the external data test set and cross-validation. The model was found to have a good predictive ability and could be used for designing similar group of compounds.

show abstract

Drug Monographs: Olaratumab and Rucaparib

Cited by 3 publications

References 21 publications

PARP1 in Carcinomas and PARP1 Inhibitors as Antineoplastic Drugs

PARP1 in Carcinomas and PARP1 Inhibitors as Antineoplastic Drugs

An assessment of poly (ADP‐ribose) polymerase‐1 role in normal and cancer cells

QSAR Model Generation of Phthalazinones as Poly (ADP-Ribose) Polymerase Inhibitors by the Genetic Algorithm and Multiple Linear Regression (GA-MLR) Method: A Ligand-Based Approach for Cancer Drug Design

Contact Info

Product

Resources

About