Protein Tyrosine Kinases: From Inhibitors to Useful Drugs (Cancer Drug Discovery and Development)

Leading researchers, from the Novartis group that pioneered Gleevec/GlivecTM and around the world, comprehensively survey the state of the art in the drug discovery processes (bio- and chemoinformatics, structural biology, profiling, generation of resistance, etc.) aimed at generating PTK inhibitors for the treatment of various diseases, including cancer. Highlights include a discussion of the rationale and the progress made towards generating "selective" low molecular-weight kinase inhibitors; an analysis of the normal function, role in disease, and application of platelet-derived growth factor antagonists; and a summary of the factors involved in successful structure-based drug design. Additional chapters address the advantages and disadvantages of in vivo preclinical models for testing protein kinase inhibitors with antitumor activity and the utility of different methods in the drug discovery and development process for determining "on-target" vs "off-target" effects of kinase inhibitors. 0003.pdf 0004.pdf 0005.pdf 0006.pdf 0007.pdf 0008.pdf 0009.pdf 0011.pdf 0012.pdf 0013.pdf 0014.pdf 0015.pdf 0017.pdf 0018.pdf 0019.pdf 0020.pdf 0021.pdf 0022.pdf 0023.pdf 0024.pdf 0025.pdf 0026.pdf 0027.pdf 0028.pdf 0029.pdf 0030.pdf 0031.pdf 0032.pdf 0033.pdf 0034.pdf 0035.pdf 0036.pdf 0037.pdf 0038.pdf 0039.pdf 0040.pdf 0041.pdf 0042.pdf 0043.pdf 0044.pdf 0045.pdf 0047.pdf 0048.pdf 0049.pdf 0050.pdf 0051.pdf 0052.pdf 0053.pdf 0054.pdf 0055.pdf 0056.pdf 0057.pdf 0058.pdf 0059.pdf 0060.pdf 0061.pdf 0062.pdf 0063.pdf 0064.pdf 0065.pdf 0066.pdf 0067.pdf 0068.pdf 0069.pdf 0070.pdf 0071.pdf 0072.pdf 0073.pdf 0074.pdf 0075.pdf 0076.pdf 0077.pdf 0078.pdf 0079.pdf 0080.pdf 0081.pdf 0082.pdf 0083.pdf 0084.pdf 0085.pdf 0087.pdf 0088.pdf 0089.pdf 0090.pdf 0091.pdf 0092.pdf 0093.pdf 0094.pdf 0095.pdf 0096.pdf 0097.pdf 0098.pdf 0099.pdf 0100.pdf 0101.pdf 0102.pdf 0103.pdf 0104.pdf 0105.pdf 0106.pdf 0107.pdf 0108.pdf 0109.pdf 0110.pdf 0111.pdf 0112.pdf 0113.pdf 0114.pdf 0115.pdf 0116.pdf 0117.pdf 0118.pdf 0119.pdf 0120.pdf 0121.pdf 0122.pdf 0123.pdf 0124.pdf 0125.pdf 0126.pdf 0127.pdf 0128.pdf 0129.pdf 0131.pdf 0132.pdf 0133.pdf 0134.pdf 0135.pdf 0136.pdf 0137.pdf 0138.pdf 0139.pdf 0140.pdf 0141.pdf 0142.pdf 0143.pdf 0144.pdf 0145.pdf 0146.pdf 0147.pdf 0148.pdf 0149.pdf 0150.pdf 0151.pdf 0152.pdf 0153.pdf 0154.pdf 0155.pdf 0156.pdf 0157.pdf 0158.pdf 0159.pdf 0160.pdf 0161.pdf 0162.pdf 0163.pdf 0164.pdf 0165.pdf 0166.pdf 0167.pdf 0168.pdf 0169.pdf 0170.pdf 0171.pdf 0172.pdf 0173.pdf 0174.pdf 0175.pdf 0176.pdf 0177.pdf 0178.pdf 0179.pdf 0180.pdf 0181.pdf 0182.pdf 0183.pdf 0184.pdf 0185.pdf 0186.pdf 0187.pdf 0188.pdf 0189.pdf 0190.pdf 0191.pdf 0192.pdf 0193.pdf 0194.pdf 0195.pdf 0196.pdf 0197.pdf 0198.pdf 0199.pdf 0200.pdf 0201.pdf 0202.pdf 0203.pdf 0204.pdf 0205.pdf 0206.pdf 0207.pdf 0208.pdf 0209.pdf 0210.pdf 0211.pdf 0212.pdf 0213.pdf 0214.pdf 0215.pdf 0216.pdf 0217.pdf 0218.pdf 0219.pdf 0220.pdf 0221.pdf 0222.pdf 0223.pdf 0224.pdf 0225.pdf 0226.pdf 0227.pdf 0228.pdf 0229.pdf 0230.pdf 0231.pdf 0232.pdf 0233.pdf 0234.pdf 0235.pdf 0236.pdf 0237.pdf 0238.pdf 0239.pdf 0240.pdf 0241.pdf 0242.pdf 0243.pdf 0244.pdf 0245.pdf 0246.pdf 0247.pdf 0248.pdf 0249.pdf 0250.pdf 0251.pdf 0252.pdf 0253.pdf 0254.pdf 0255.pdf 0256.pdf 0257.pdf 0258.pdf 0259.pdf 0260.pdf 0261.pdf 0262.pdf 0263.pdf 0264.pdf 0265.pdf 0266.pdf 0267.pdf 0268.pdf 0269.pdf 0270.pdf 0271.pdf 0272.pdf 0273.pdf 0274.pdf 0275.pdf 0276.pdf 0277.pdf 0278.pdf 0279.pdf 0280.pdf 0281.pdf 0282.pdf 0283.pdf 0284.pdf 0285.pdf 0286.pdf 0287.pdf 0288.pdf 0289.pdf 0290.pdf 0291.pdf 0292.pdf 0293.pdf 0294.pdf 0295.pdf 0296.pdf 0297.pdf 0298.pdf 0299.pdf 0300.pdf 0301.pdf 0302.pdf 0303.pdf 0304.pdf 0305.pdf 0306.pdf

Protein kinases function as components of signal transduction pathways, playing a central role in the control of cell growth, metabolism, differentiation, and apoptosis. The development of selective protein tyrosine kinase (PTK) inhibitors that can block or modulate diseases, such as cancer, with abnormalities in these signaling pathways is considered a promising approach for drug development. Currently, more than 20 different PTKs are being considered as potential therapeutic targets in oncology. In Protein Tyrosine Kinases: From Inhibitors to Useful Drugs, leading researchers from the Novartis group that pioneered Gleevec/Glivec™ and from around the world comprehensively survey the state-of-the-art in the drug discovery processes (bio- and chemoinformatics, structural biology, profiling, generation of resistance, etc.) aimed at generating PTK inhibitors for the treatment of various diseases, including cancer. Highlights include a discussion of the rationale and the progress made toward generating selective low molecular-weight kinase inhibitors; an analysis of the normal function, role in disease, and application of platelet-derived growth factor antagonists; and a summary of the factors involved in successful structure-based drug design. Additional chapters address the advantages and disadvantages of in vivo preclinical models for testing PTK inhibitors with antitumor activity and the utility of different methods in the drug discovery and development process for determining on-target vs off-target effects of kinase inhibitors.

Authoritative and state-of-the-art, Protein Tyrosine Kinases: From Inhibitors to Useful Drugs details the key stages in the design of PTK inhibitors and their development into useful drugs.

Protein tyrosine kinases as targets for cancer and other indications / Mark Pearson, Carlos Garcia-Echeverria, Doriano Fabbro Inhibitors of signaling interfaces: targeting Src homology 2 domains in drug discovery / Carlos Garcia-Echeverria PI 3-kinase inhibition: a target for therapeutic intervention / Peter M. Finan, Stephen G. Ward Src as a target for pharmaceutical intervention: potential and limitations / Mira Susa ... [et al.] Activated FLT3 receptor tyrosine kinase as a therapeutic target in leukemia / Blanca Scheijen, James D. Griffin JAK kinases in leukemias/lymphomas and multiple myeloma / Renate Burger, Martin Gramatzki Glivec (Gleevec, Imatinib, STI571): a targeted therapy for CML / Elisabeth Buchdunger, Renaud Capedeville Platelet-derived growth factor: normal function, role in disease, and applications of PDGF antagonists / Tobias Sjoblom ... [et al.] Structural biology of protein tyrosine kinases / Sandra W. Cowan-Jacob ... [et al.] Testing of signal transduction inhibitors in animal models of cancer / Terence O'Reilly, Robert Cozens Phosphoproteomics in drug discovery and development / Michel F. Moran. In this title, leading researchers, from the Novartis group that pioneered Gleevec/Gliveca and around the world, comprehensively survey the state of the art in the drug discovery processes (bio- and chemoinformatics, structural biology, profiling, generation of resistance, etc.) aimed at generating PTK inhibitors for the treatment of various diseases, including cancer. Highlights include a discussion of the rationale and the progress made towards generating 'selective' low molecular-weight kinase inhibitors; an analysis of the normal function, role in disease, and application of platelet-deriv