GLOSSARY

Abl kinase

An intracellular tyrosine kinase, c-Abl is the endogenous cellular counterpart to the Abelson Virus tyrosine kinase (v-Abl). The inadvertent activation of Abl kinase results in Chronic Myelogenous Leukemia (CML). See also BCR/ABL.

Apoptosis

A form of programmed cell death (PCD; see below), by which an orchestrated series of biochemical events takes place within cells leading ultimately to cell death.

BCR/ABL

A fusion protein of BCR and Abl, the result of a gene translocation, that is associated with Chronic Myelogenous Leukemia (CML).

Chronic Myelogenous Leukemia (CML)

A form of chronic leukemia characterized by increased and unregulated proliferation of cells in the bone marrow.

DNA-Programmed Chemistry™ (DPC™)

The technology platform invented by Professor David Liu at Harvard University that uses the specific formation of double stranded DNA to control chemical reactions.

EGFR

Epidermal Growth Factor (EGF) Receptor. See also ERBB

ERBB

A family of receptor tyrosine kinases (RTKs) related to the EGF Receptor (see EGFR), members of which include ERBB1 (EGFR), ERBB2 (HER2), ERBB3 and ERBB4. These receptors are important in cell-cell communication controlling the growth of cells and tissues, and are important targets of new anti-cancer drugs such as Herceptin®.

Herceptin®

See Trastuzumab.

Lipinski Rule of 5

A set of guidelines devised by Dr. Chris Lipinski that indicate the preferred physicochemical properties of molecules that influence compound solubility and cell permeability.

Macrocycle

An organic molecule that contains a ring structure of more than 12 atoms.

Programmed cell death (PCD)

The natural physiological process of cell suicide, involved in controlling development and cell numbers. This process is often inhibited in cancer cells, leading to the growth of tumors and resistance to anti-cancer drugs. PCD is most often carried out within cells by the process of apoptosis (see above).

Protein tyrosine phosphatase (PTP)

A class of enzymes that removes phosphate groups from tyrosine residues of proteins. The activity of these enzymes is generally the reverse of tyrosine kinases. Tyrosine kinases and phosphatases together regulate the structure and function of proteins via the phosphorylation state of the protein’s tyrosine residues.

Receptor tyrosine kinase

A class of cell surface transmembrane receptors that signal via their cytoplasmic kinase domains. Many respond to extracellular signals from growth factors such as epidermal growth factor and platelet-derived growth factor, translating the extracellular signal from these ligands into an intracellular kinase signaling cascade.

SAR

Structure-Activity Relationship. Used by medicinal chemists and pharmacologists to describe the relationship between variations in chemical structure and a specific biochemical or physiological activity of a molecule such as its binding affinity for a target or its inhibitory activity on an enzyme.

Trastuzumab

Generic name for Herceptin®, an inhibitory humanized monoclonal antibody targeted to the extracellular domain of ERBB2.