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Some approaches attempt to stop the functioning of the pathway in the diseased state by causing a key molecule to stop functioning. Drugs may be designed that bind to the active region and inhibit this key molecule. However these drugs would also have to be designed in such a way as not to affect any other important molecules that may be similar in appearance to the key molecules. Sequence homologies are often used to identify such risks.
Other approaches may be to enhance the normal pathway by promoting specific molecules in the normal pathways that may have been affected in the diseased state.
The structure of the drug molecule that can specifically interact with the biomolecules can be attempted using computational tools. These tools can allow a drug molecule to be constructed within the biomolecule using knowledge of its structure and the nature of its active site. Construction of the drug molecule can be made inside out or outside in depending on whether the core or the R-group s are chosen first. However many of these approaches are plagued by the practical problems of chemical synthesis.
There are also serious concerns on whether these approaches are 'philosophically correct' in their approach to actually curing a condition since they often target symptoms rather than causes.
Newer approaches have also suggested the use of drug molecules that are large and proteinaceous in nature rather than as small molecules. There have also been suggestions to make these using mRNA. Gene silencing may also have therapeutical applications.
Unlike the historical method of drug discovery, by trial-and-error testing of chemical substances on animals, and matching the apparent effects to treatments, rational drug design begins with a knowledge of specific chemical responses in the body, and tailoring combinations of these to fit a treatment profile.
An important case study in rational drug design is imatinibImatinib is a new drug used to treat certain types of cancer. It is a kind of chemotherapy used in treating chronic myelogenous leukemia (CML), gastrointestinal stromal tumors (GISTs) and a number of other malignancies. It is occasionally referred to as C, a tyrosine kinaseTyrosine kinases are a subclass of protein kinase, see there for the principles of protein phosphorylation A tyrosine kinase (EC 2. 112) is an enzyme that can transfer a phosphate group to a tyrosine residue in a protein; these enzymes are a subgroup of t inhibitor designed specifically for the bcr-abl fusion protein that is characteristic for Philadelphia chromosomePhiladelphia chromosome or Philadelphia translocation is a specific genetic, chromosomal abnormality that is associated with chronic myelogenous leukemia (CML). 95% of patients with CML show this abnormality; a remaining 2-3% harbor a very similar abnorma-positive leukemiaLeukemia leukaemia in international English) is a group of cancers of the blood-forming tissues. The word leukemia tends to be used as an umbrella term. In the 19th century, it was seen as one single, homogenous deadly disease, characterized by a white aps ( chronic myelogenous leukemiaA form of leukemia, chronic myelogenous leukemia (or CML is a clonal stem cell disorder characterized by excessive proliferation of myeloid cells. Signs and symptoms The disease is often without specific symptoms. Often it is detected on a routine full bl and occasionally acute lymphocytic leukemiaAcute lymphocytic leukaemia ALL , also known as acute lymphoblastic leukaemia is a cancer of the white blood cells, characterised by the overproduction and continuous multiplication of malignant and immature white blood cells (referred to as lymphoblasts)). Imatinib is substantially different from previous drugs for cancerFor other meanings of Cancer: see Cancer (disambiguation . apoptosis; cancer cells, however, avoid apoptosis. Cancer is a group of related diseases characterized by uncontrolled cell division. Currently, it is believed that cancers arise from both genetic, as most agents of chemotherapyChemotherapy (pronounced keem-o-therapy is the use of certain drugs to treat disease, as distinct from other forms of treatment, such as surgery. Chemotherapy dates at least as far back as the use, by the Indians of Peru, of cinchona bark in the treatment simply target rapidly dividing cells, not differentiating between cancer cells and other tissues.