ChemCore offers synthetic chemistry, medicinal chemistry, cheminformatics and molecular modeling services to support chemical biology and translational research programs. Our expertise is in the design and synthesis of bioactive small molecules and supports both basic cancer biology research and the translation of basic research findings into effective anticancer agents.
Silverman Hall, 3557
2170 Campus Drive
Evanston, IL 60208
- Tarry Building 12-715
300 E. Superior Street
Chicago, IL 60611
Services & Equipment
Cheminformatics and Molecular Modeling service utilizes advanced computational tools and techniques to study ligand-protein and protein-protein interactions. Specifically, our capabilities include:
- Using structure and ligand-based algorithms to identify novel drug-like molecules for various disease targets using our virtual high-throughput screening platform
- Virtual screening millions of compounds against a new protein target with the goal of generating a new lead compound or identifying a known drug with a potentially new off-target effect
- Constructing homology models of proteins in the absence of a crystal structure
- Generating qualitative structure activity relationships
- Utilizing well-validated methods to investigate ADME-tox properties of new chemical entities
- Performing advanced computational analyses such as high-level quantum mechanics calculations and molecular dynamics simulations
Medicinal and Synthetic Chemistry service carries out the design and synthesis of new small molecules for drug discovery projects as well as for use as molecular probes to study biological processes. It is performed by highly experienced professional medicinal and synthetic chemists who use state-of-the-art equipment and approaches. Our capabilities also include synthesis of reference compounds and preparation of fluorescently-tagged molecules.
Consultation is available to help investigators advance their research through the use of chemistry and related molecular approaches. We are able to help design and develop small molecule drug discovery programs, search chemistry and patent literature, develop hit identification strategies, analyze and prioritize HTS data, assess ADME, PK/PD, toxicology properties and consult on other aspects related to developing small molecule therapeutics.
- Acquity UPLC H-Class System
- Agilent mass-directed analytical to preparative HPLC
- Gilson Preparative HPLC System with GX-27L liquid handler
- Biotage Isolera Flash chromatography
- Agilent 1260 analytical HPLC with UV and ELS detection
- Agilent 1200 preparative HPLC
- Biotage V10 Touch and Genevac centrifugal evaporators
- Multiple Linux-based NVIDIA GPU workstations and a high-performance computing cluster equipped with Certara, Schrodinger and Dassault Systems BIOVIA software
Discovery of selective MAP2K4 inhibitors as a novel strategy for combating tumor metastasis.
Dr. Karl Scheidt (CAPS) in collaboration with Dr. Ray Bergan, Oregon Health & Science University, developed new and selective MAP2K4 inhibitors to inhibit prostate cancer metastasis. ChemCore contributed to their work by helping create a robust inhibitor-screening platform to inform the discovery and design of new and potent inhibitors of MAP2K4, a kinase that is overexpressed in metastatic prostate cancers. Our medicinal chemistry expertise was applied to triage compounds for screening with a high-throughput fluorescent thermal shift assay and prioritize hits. Our cheminformatics capabilities were essential to developing accurate quantitative structure-activity relationship (QSAR) models for predicting potency of potential new inhibitors prior to being synthesized and tested. Results from a follow-up study by Drs. Scheidt and Bergan show how known inhibitors interact with each kinase of the MAP2K family which has led their team to developing novel inhibitors for MAP2K4. ChemCore’s advanced molecular modeling technques were applied to guide the design of new potent and selective MEK4 hit analogs.
Grant support: NCI R01CA188015
- Krishna SN, Luan CH, Mishra RK, Xu L, Scheidt KA, Anderson WF, Bergan RC. A fluorescence-based thermal shift assay identifies inhibitors of mitogen activated protein kinase kinase 4. PLoS One. 8: e81504, 2013. PMCID: PMC3855329.
- Deibler, KK, Mishra, RK, Clutter MR, Antanasjivec, A, Bergan R, Caffrey, M., Scheidt KA. A chemical probe strategy for interrogating inhibitor selectivity across the MEK kinase family. ACS Chem Biol. 12:1245, 2017.
Discovery and development of the first small molecule CXCR4 agonists for the treatment for AML.
Collaborative work by Dr. Gary Schiltz (CAPS) and Dr. Richard Miller (MOM) led to the synthesis of a series of small molecule CXCR4 agonists, offering a new strategy for targeting CXCR4-dependent cancers. These agonists were identified using a combination of structure- and ligand-based vHTS in ChemCore. In further work that involved collaboration with Drs. Jessica Altman (HM) and Leonidas Platanias (HM), several of these agonists were found to induce chemosensitization of leukemia cells to chemotherapy. We have developed a lead series of compounds which are undergoing lead optimization to improve potency and efficacy as a potential AML therapeutics.
Grant support: NCI R01CA189074
Mishra RK, Shum AK, Platanias LC, Miller RJ, Schiltz, GE. Discovery and characterization of novel small-molecule CXCR4 receptor agonists and antagonists. Sci Rep. 6:30155, 2016. PMCID: PMC4960487. Patent application: PCT/US16/30891
All manuscripts and grants presenting work supported by this core should include the following acknowledgement:
[Description of work] was performed by ChemCore at the Center for Molecular Innovation and Drug Discovery at Northwestern University. ChemCore is generously supported by NCI CCSG P30 CA060553 awarded to the Robert H. Lurie Comprehensive Cancer Center.