;The Drug Discovery and Structural Biology Core (DDSB) is a new shared resource that supports the identification and development of small molecule and macromolecular therapeutics for the basic, translational and clinical scientists at COHCCC. The overarching goal of DDSB is to provide the necessary scientific resources to assist In chemical biology studies and development of molecularly-based therapeutics. DDSB comprises several scientific disciplines that include medicinal chemistry, biopolymer synthesis, high throughput screening, and X-ray crystallography. Rather than have separate cores for each, these disciplines are consolidated under one unit for maximum efficiency in drug development. This has resulted in unique shared resource that works in concert to achieve the basic and translational research goals of the Cancer Center. Specific areas of expertise and services provided include: synthetic organic chemistry, custom synthesis of specialized RNA and DNA, assay development, high-throughput screening, protein production, biophysical characterization and structural biology. The amalgamation of these services provides a seamless drug discovery pipeline for development of novel molecular targets. The DDSB core is focused yet flexible to allow Cancer Center members to use any one of these services individually or in combination. An additional significant component of the DDSB is to consult with Pis, develop reagents and assays, and obtain preliminary results to support the application of externally funded proposals by Cancer Center members. For example, the DDSB has developed COH29, a novel small-molecule inhibitor that is a dual PARP/rlbonucleotide reductase antagonist and has promising activity against BRCA1 deficient cancers. This work has led to new ROI funding and our first drug candidate for GMP synthesis and clinical trials developed completely in-house. Collectively, the DDSB serves as a scientific and intellectual hub for Integrating diverse disciplines such as molecular modeling, bioinformatics, and pharmacology in a transdisciplinary approach towards the development of new agents for the treatment of cancer. The DDSB Is unique in this capacity as it provides a complete program of scientific services and coordination of efforts for drug discovery in an academic setting. Thus, Pis can leverage the DDSB core for pursuing avenues of research not previously available at one site in an academic center, thereby accelerating the development of chemical biology probes and molecularly-targeted therapies for clinic trials at COHCCC.

Public Health Relevance

The overall goal of the Drug Discovery and Structural Biology core facility is to support drug development efforts within COHCCC, utilizing advanced capabilities and equipment to develop next-generation, molecularly-targeted cancer therapeutics. This goal promotes the Cancer Center's dedication to developing innovative new disease-fighting strategies In the battle against cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
5P30CA033572-31
Application #
8764851
Study Section
Subcommittee G - Education (NCI)
Project Start
Project End
Budget Start
2013-12-01
Budget End
2014-11-30
Support Year
31
Fiscal Year
2014
Total Cost
$156,449
Indirect Cost
$63,325
Name
City of Hope/Beckman Research Institute
Department
Type
DUNS #
027176833
City
Duarte
State
CA
Country
United States
Zip Code
91010
Vu, Binh Thanh; Shahin, Sophia Allaf; Croissant, Jonas et al. (2018) Chick chorioallantoic membrane assay as an in vivo model to study the effect of nanoparticle-based anticancer drugs in ovarian cancer. Sci Rep 8:8524
Ambaye, Nigus; Chen, Chih-Hong; Khanna, Swati et al. (2018) Streptonigrin Inhibits SENP1 and Reduces the Protein Level of Hypoxia-Inducible Factor 1? (HIF1?) in Cells. Biochemistry 57:1807-1813
Bosworth, Alysia; Goodman, Elizabeth L; Wu, Eric et al. (2018) The Minneapolis-Manchester Quality of Life Instrument: reliability and validity of the Adult Form in cancer survivors. Qual Life Res 27:321-332
Pang, Ka Ming; Castanotto, Daniela; Li, Haitang et al. (2018) Incorporation of aptamers in the terminal loop of shRNAs yields an effective and novel combinatorial targeting strategy. Nucleic Acids Res 46:e6
Yan, Wei; Wu, Xiwei; Zhou, Weiying et al. (2018) Cancer-cell-secreted exosomal miR-105 promotes tumour growth through the MYC-dependent metabolic reprogramming of stromal cells. Nat Cell Biol 20:597-609
Li, Sihui; Ali, Shafat; Duan, Xiaotao et al. (2018) JMJD1B Demethylates H4R3me2s and H3K9me2 to Facilitate Gene Expression for Development of Hematopoietic Stem and Progenitor Cells. Cell Rep 23:389-403
Nguyen, Huong Q; Ruel, Nora; Macias, Mayra et al. (2018) Translation and Evaluation of a Lung Cancer, Palliative Care Intervention for Community Practice. J Pain Symptom Manage 56:709-718
Mendez-Dorantes, Carlos; Bhargava, Ragini; Stark, Jeremy M (2018) Repeat-mediated deletions can be induced by a chromosomal break far from a repeat, but multiple pathways suppress such rearrangements. Genes Dev 32:524-536
Bzymek, Krzysztof P; Puckett, James W; Zer, Cindy et al. (2018) Mechanically interlocked functionalization of monoclonal antibodies. Nat Commun 9:1580
Sun, Jie; He, Xin; Zhu, Yinghui et al. (2018) SIRT1 Activation Disrupts Maintenance of Myelodysplastic Syndrome Stem and Progenitor Cells by Restoring TET2 Function. Cell Stem Cell 23:355-369.e9

Showing the most recent 10 out of 1396 publications