chemical genomics – biol503 lecture 2 chemical genomics and cancer/cardiovascular diseases
Post on 19-Dec-2015
215 views
TRANSCRIPT
![Page 1: Chemical Genomics – Biol503 Lecture 2 Chemical Genomics and cancer/cardiovascular diseases](https://reader030.vdocuments.us/reader030/viewer/2022032704/56649d3f5503460f94a18b71/html5/thumbnails/1.jpg)
Chemical Genomics – Biol503
Lecture 2Chemical Genomics and cancer/cardiovascular
diseases
![Page 2: Chemical Genomics – Biol503 Lecture 2 Chemical Genomics and cancer/cardiovascular diseases](https://reader030.vdocuments.us/reader030/viewer/2022032704/56649d3f5503460f94a18b71/html5/thumbnails/2.jpg)
Anticancer Drug Screen
![Page 3: Chemical Genomics – Biol503 Lecture 2 Chemical Genomics and cancer/cardiovascular diseases](https://reader030.vdocuments.us/reader030/viewer/2022032704/56649d3f5503460f94a18b71/html5/thumbnails/3.jpg)
Traditional Approach: cell growth inhibition
Screen of synthetic and natural product compound libraries for inhibitor of cancer cell-lines
NCI’s cancer cell-lines (free) NCI’s Open Chemical Repository
Collection (140,000 compounds) NCI’s Natural Products Repository
![Page 4: Chemical Genomics – Biol503 Lecture 2 Chemical Genomics and cancer/cardiovascular diseases](https://reader030.vdocuments.us/reader030/viewer/2022032704/56649d3f5503460f94a18b71/html5/thumbnails/4.jpg)
Protein Kinases – cancer and cardiovascular diseases
![Page 5: Chemical Genomics – Biol503 Lecture 2 Chemical Genomics and cancer/cardiovascular diseases](https://reader030.vdocuments.us/reader030/viewer/2022032704/56649d3f5503460f94a18b71/html5/thumbnails/5.jpg)
Cancer Pathways – cellular targets
Source: Prous Integrity
![Page 6: Chemical Genomics – Biol503 Lecture 2 Chemical Genomics and cancer/cardiovascular diseases](https://reader030.vdocuments.us/reader030/viewer/2022032704/56649d3f5503460f94a18b71/html5/thumbnails/6.jpg)
Phosphorylation
Phosphorylation by protein kinases is the most widespread and well-studied signal mechanisms in eukaryotic cells
Kinome: 518 kinases, each phosporylates a distinct set of substrates
Understanding complex network of kinase-based signaling is important for cancer and cardiovascular diseases
![Page 7: Chemical Genomics – Biol503 Lecture 2 Chemical Genomics and cancer/cardiovascular diseases](https://reader030.vdocuments.us/reader030/viewer/2022032704/56649d3f5503460f94a18b71/html5/thumbnails/7.jpg)
Kinase assay – an example
Time resolved FRET
![Page 8: Chemical Genomics – Biol503 Lecture 2 Chemical Genomics and cancer/cardiovascular diseases](https://reader030.vdocuments.us/reader030/viewer/2022032704/56649d3f5503460f94a18b71/html5/thumbnails/8.jpg)
Approved drug: an example
Tykerb (lapatinib ditosylate) is an EGFR and ErbB-2 dual tyrosince kinase inhibitor.
EGFR- epidermal growth factor receptor ErbB-2 (HER2/neu) – Human Epidermal
growth factor Receptor 2 Developed by GlaxoSmithKline Approved by FDA March 2007 for use in
combination with capectabine for patients with advanced, metastatic breast cancer that is HER2 positive.
![Page 9: Chemical Genomics – Biol503 Lecture 2 Chemical Genomics and cancer/cardiovascular diseases](https://reader030.vdocuments.us/reader030/viewer/2022032704/56649d3f5503460f94a18b71/html5/thumbnails/9.jpg)
Protein Tyrosine Phosphatases – cancer and cardiovascular
diseases
![Page 10: Chemical Genomics – Biol503 Lecture 2 Chemical Genomics and cancer/cardiovascular diseases](https://reader030.vdocuments.us/reader030/viewer/2022032704/56649d3f5503460f94a18b71/html5/thumbnails/10.jpg)
Protein tyrosince phosphatases
The PTP superfamily of enzymes functions in a coordinated manner with protein tyrosine kinases to control signal pathways
Regulatory role of protein kinases well established.
But protein phosphatases can no longer viewed as passive housekeeping enzymes in the processes.
![Page 11: Chemical Genomics – Biol503 Lecture 2 Chemical Genomics and cancer/cardiovascular diseases](https://reader030.vdocuments.us/reader030/viewer/2022032704/56649d3f5503460f94a18b71/html5/thumbnails/11.jpg)
Diversity of PTPs
![Page 12: Chemical Genomics – Biol503 Lecture 2 Chemical Genomics and cancer/cardiovascular diseases](https://reader030.vdocuments.us/reader030/viewer/2022032704/56649d3f5503460f94a18b71/html5/thumbnails/12.jpg)
Regulation by dimerization
![Page 13: Chemical Genomics – Biol503 Lecture 2 Chemical Genomics and cancer/cardiovascular diseases](https://reader030.vdocuments.us/reader030/viewer/2022032704/56649d3f5503460f94a18b71/html5/thumbnails/13.jpg)
Regulation by Ligands
![Page 14: Chemical Genomics – Biol503 Lecture 2 Chemical Genomics and cancer/cardiovascular diseases](https://reader030.vdocuments.us/reader030/viewer/2022032704/56649d3f5503460f94a18b71/html5/thumbnails/14.jpg)
PTPs and Cancers
![Page 15: Chemical Genomics – Biol503 Lecture 2 Chemical Genomics and cancer/cardiovascular diseases](https://reader030.vdocuments.us/reader030/viewer/2022032704/56649d3f5503460f94a18b71/html5/thumbnails/15.jpg)
ProFluor Assay
![Page 16: Chemical Genomics – Biol503 Lecture 2 Chemical Genomics and cancer/cardiovascular diseases](https://reader030.vdocuments.us/reader030/viewer/2022032704/56649d3f5503460f94a18b71/html5/thumbnails/16.jpg)
References
Johnson and Hunter, Nature Methods, 2005
N.K. Tonks, Nature Review Mol Cell Biol, 2006