;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
Aslamy, Arianne; Oh, Eunjin; Ahn, Miwon et al. (2018) Exocytosis Protein DOC2B as a Biomarker of Type 1 Diabetes. J Clin Endocrinol Metab 103:1966-1976
Abeywardana, Tharindumala; Oh, Myungeun; Jiang, Lei et al. (2018) CARM1 suppresses de novo serine synthesis by promoting PKM2 activity. J Biol Chem 293:15290-15303
Sun, Virginia; Crane, Tracy E; Slack, Samantha D et al. (2018) Rationale, development, and design of the Altering Intake, Managing Symptoms (AIMS) dietary intervention for bowel dysfunction in rectal cancer survivors. Contemp Clin Trials 68:61-66
Li, Daneng; McCall, Linda M; Hahn, Olwen M et al. (2018) Identification of risk factors for toxicity in patients with hormone receptor-positive advanced breast cancer treated with bevacizumab plus letrozole: a CALGB 40503 (alliance) correlative study. Breast Cancer Res Treat 171:325-334
Caserta, Enrico; Chea, Junie; Minnix, Megan et al. (2018) Copper 64-labeled daratumumab as a PET/CT imaging tracer for multiple myeloma. Blood 131:741-745
Smith, Nicholas R; Swain, John R; Davies, Paige S et al. (2018) Monoclonal Antibodies Reveal Dynamic Plasticity Between Lgr5- and Bmi1-Expressing Intestinal Cell Populations. Cell Mol Gastroenterol Hepatol 6:79-96
Jandial, Rahul; Neman, Josh; Lim, Punnajit P et al. (2018) Inhibition of GLO1 in Glioblastoma Multiforme Increases DNA-AGEs, Stimulates RAGE Expression, and Inhibits Brain Tumor Growth in Orthotopic Mouse Models. Int J Mol Sci 19:
Herrera, A F; Palmer, J; Martin, P et al. (2018) Autologous stem-cell transplantation after second-line brentuximab vedotin in relapsed or refractory Hodgkin lymphoma. Ann Oncol 29:724-730
Choi, Audrey H; O'Leary, Michael P; Lu, Jianming et al. (2018) Endogenous Akt Activity Promotes Virus Entry and Predicts Efficacy of Novel Chimeric Orthopoxvirus in Triple-Negative Breast Cancer. Mol Ther Oncolytics 9:22-29
Kumar, B; Garcia, M; Weng, L et al. (2018) Acute myeloid leukemia transforms the bone marrow niche into a leukemia-permissive microenvironment through exosome secretion. Leukemia 32:575-587

Showing the most recent 10 out of 1396 publications