You have been asked to design a drug to inhibit BCR-ABL in an effort to treat CML. Using your knowledge of enzyme-catalyzed reactions and the BCR-ABL kinase, propose a drug development strategy to combat CML. (Regular Abl protein is regulated by other molecules. BRC-ABL has mutant kinase that leads to cancer.)

by designing a drug with steric effects on BCR-ABL1

Explanation:

Chronic myeloid leukemia (CML)  is a type of cancer that affects the bone marrow and blood cells. CML is characterized by the formation of the Philadelphia chromosome, a product of a reciprocal translocation between chromosomes 9 and 22. As a consequence of this translocation, an oncoprotein tyrosine kinase called BCR-ABL1 is formed. This protein (BCR-ABL1) is responsible for 95% of all CMLs. In this case, it is possible to inhibit BCR-ABL1 (and thus inhibit CML cell proliferation) by using a kinase inhibitor. Kinase inhibitors are drugs that inhibit kinase function by preferentially binding to the inactive conformation of the target enzyme. These proteins are used to treat cancer by blocking a functional site on the kinase, thereby inhibiting its function. Moreover, it is known that steric effects alter the mode and rate by which a drug interacts with a given target. In this case, a small molecule with steric effects on BCR-ABL1, i.e., capable of altering the shape (conformation) and reactivity of BCR-ABL1, might also be used to selectively inhibit BCR-ABL1.

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