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Literature DB >> 27781374

Recent Developments Using Small Molecules to Target RAD51: How to Best Modulate RAD51 for Anticancer Therapy?

Brian Budke¹, Wei Lv², Alan P Kozikowski², Philip P Connell¹.

Abstract

Homologous recombination (HR) is an evolutionarily conserved DNA repair process. Overexpression of the key HR protein RAD51 is a common feature of malignant cells. RAD51 plays two distinct genome-stabilizing roles, including HR-mediated repair of double-strand breaks (DSBs) and the promotion of replication fork stability during replication stress. Because upregulation of RAD51 in cancer cells can promote tumor resistance to DNA-damaging oncologic therapies, we and others have worked to develop cancer therapeutics that target various aspects of RAD51 protein function. Herein, we provide an overview of recent developments in this field, together with our perspectives on the challenges associated with these evolving anticancer strategies.

Entities: Chemical Disease Gene Mutation Species

Keywords: RAD51; cancer therapy; drug discovery; homologous recombination; medicinal chemistry

Mesh：

Substances：

Year: 2016 PMID： 27781374 PMCID： PMC5472043 DOI： 10.1002/cmdc.201600426

Source DB: PubMed Journal: ChemMedChem ISSN： 1860-7179 Impact factor: 3.466

53 in total

1. Gleevec-mediated inhibition of Rad51 expression and enhancement of tumor cell radiosensitivity.

Authors: Jeffery S Russell; Kristin Brady; William E Burgan; Michael A Cerra; Kelli A Oswald; Kevin Camphausen; Philip J Tofilon
Journal: Cancer Res Date: 2003-11-01 Impact factor: 12.701

Review 2. Replication protein A: a heterotrimeric, single-stranded DNA-binding protein required for eukaryotic DNA metabolism.

Authors: M S Wold
Journal: Annu Rev Biochem Date: 1997 Impact factor: 23.643

3. Double-strand break repair-independent role for BRCA2 in blocking stalled replication fork degradation by MRE11.

Authors: Katharina Schlacher; Nicole Christ; Nicolas Siaud; Akinori Egashira; Hong Wu; Maria Jasin
Journal: Cell Date: 2011-05-13 Impact factor: 41.582

4. Model for homologous recombination during transfer of DNA into mouse L cells: role for DNA ends in the recombination process.

Authors: F L Lin; K Sperle; N Sternberg
Journal: Mol Cell Biol Date: 1984-06 Impact factor: 4.272

5. Rad51 siRNA delivered by HVJ envelope vector enhances the anti-cancer effect of cisplatin.

Authors: Makoto Ito; Seiji Yamamoto; Keisuke Nimura; Kazuya Hiraoka; Katsuto Tamai; Yasufumi Kaneda
Journal: J Gene Med Date: 2005-08 Impact factor: 4.565

6. Defects in XRCC4 and KU80 differentially affect the joining of distal nonhomologous ends.

Authors: Josée Guirouilh-Barbat; Emilie Rass; Isabelle Plo; Pascale Bertrand; Bernard S Lopez
Journal: Proc Natl Acad Sci U S A Date: 2007-12-18 Impact factor: 11.205

7. Use of the Rad51 promoter for targeted anti-cancer therapy.

Authors: Christopher M Hine; Andrei Seluanov; Vera Gorbunova
Journal: Proc Natl Acad Sci U S A Date: 2008-12-23 Impact factor: 11.205

8. Development of Small Molecules that Specifically Inhibit the D-loop Activity of RAD51.

Authors: Wei Lv; Brian Budke; Michal Pawlowski; Philip P Connell; Alan P Kozikowski
Journal: J Med Chem Date: 2016-04-21 Impact factor: 7.446

9. A Small-Molecule Inhibitor of RAD51 Reduces Homologous Recombination and Sensitizes Multiple Myeloma Cells to Doxorubicin.

Authors: David A Alagpulinsa; Srinivas Ayyadevara; Robert Joseph Shmookler Reis
Journal: Front Oncol Date: 2014-10-30 Impact factor: 6.244

10. DIDS, a chemical compound that inhibits RAD51-mediated homologous pairing and strand exchange.

Authors: Takako Ishida; Yoshimasa Takizawa; Takashi Kainuma; Jin Inoue; Tsutomu Mikawa; Takehiko Shibata; Hidekazu Suzuki; Satoshi Tashiro; Hitoshi Kurumizaka
Journal: Nucleic Acids Res Date: 2009-03-30 Impact factor: 16.971

19 in total

1. Radiation-induced synthetic lethality: combination of poly(ADP-ribose) polymerase and RAD51 inhibitors to sensitize cells to proton irradiation.

Authors: Anne-Catherine Wéra; Alison Lobbens; Miroslav Stoyanov; Stéphane Lucas; Carine Michiels
Journal: Cell Cycle Date: 2019-06-25 Impact factor: 4.534

Recent Developments Using Small Molecules to Target RAD51: How to Best Modulate RAD51 for Anticancer Therapy?

1. Gleevec-mediated inhibition of Rad51 expression and enhancement of tumor cell radiosensitivity.

Review 2. Replication protein A: a heterotrimeric, single-stranded DNA-binding protein required for eukaryotic DNA metabolism.

3. Double-strand break repair-independent role for BRCA2 in blocking stalled replication fork degradation by MRE11.

4. Model for homologous recombination during transfer of DNA into mouse L cells: role for DNA ends in the recombination process.

5. Rad51 siRNA delivered by HVJ envelope vector enhances the anti-cancer effect of cisplatin.

6. Defects in XRCC4 and KU80 differentially affect the joining of distal nonhomologous ends.

7. Use of the Rad51 promoter for targeted anti-cancer therapy.

8. Development of Small Molecules that Specifically Inhibit the D-loop Activity of RAD51.

9. A Small-Molecule Inhibitor of RAD51 Reduces Homologous Recombination and Sensitizes Multiple Myeloma Cells to Doxorubicin.

10. DIDS, a chemical compound that inhibits RAD51-mediated homologous pairing and strand exchange.

1. Radiation-induced synthetic lethality: combination of poly(ADP-ribose) polymerase and RAD51 inhibitors to sensitize cells to proton irradiation.

2. RADX Promotes Genome Stability and Modulates Chemosensitivity by Regulating RAD51 at Replication Forks.

Review 3. Repurposing Drugs for Cancer Radiotherapy: Early Successes and Emerging Opportunities.

Review 4. RAD51 Gene Family Structure and Function.

Review 5. Small-Molecule Inhibitors Targeting DNA Repair and DNA Repair Deficiency in Research and Cancer Therapy.

6. TdT-dUTP DSB End Labeling (TUDEL), for Specific, Direct In Situ Labeling of DNA Double Strand Breaks.

7. Expression, Purification, and Biochemical Evaluation of Human RAD51 Protein.

8. Observation and Analysis of RAD51 Nucleation Dynamics at Single-Monomer Resolution.

Review 9. The Role of PARP Inhibitors in the Treatment of Prostate Cancer: Recent Advances in Clinical Trials.

Review 10. Small-molecule drug repurposing to target DNA damage repair and response pathways.