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Acute Leukemia Forum 2000, Advances and Controversies in the Therapy of Acute Myelogenous Leukemia

Small molecule mimics of hematopoietic growth factors: improving on Mother Nature?

Leukemia volume 15, pages 673–674 (2001)Cite this article

Recently, a number of screening methods have been developed to identify small molecules that might mimic the biological effects of hematopoietic growth factors. The potential advantages of small molecule mimics include lack of immunogenicity, fewer drug side-effects, and nonparenteral routes of administration. Small molecules might also be less expensive to produce. Disadvantages include shorter half-life compared to larger proteins and differences in potency.

The theoretical basis to attempt to design or screen for small molecule mimics of hematopoietic growth factors lies in multiple studies demonstrating that several types of molecules not related to growth factors can dimerize growth factor receptor subunits and induce signal transduction, thereby mimicking the biological effects of hematopoietic growth factors. Duplication of growth factor binding sites in a single molecule can initiate engagement of two receptor molecules and initiate signaling (as shown for erythropoietin (EPO)), as can the binding of bivalent monoclonal antibodies against receptor subunits (many examples). Similarly, mutations in the receptors themselves (EPO, thrombopoietin (TPO)) can initiate dimerization and cellular activation. Exogenous molecules such as the gp55 of the Friend leukemia virus can naturally dimerize the EPO receptor and lead to signal transduction. These results suggest that small molecule mimetics may be designed which can initiate signal transduction and demonstrate similar biological activity as the native growth factor.

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  1. Division of Hematology, University of Washington, Box 357710, 1959 NE Pacific Street, Seattle, WA 98195, USA

    K Kaushansky

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  1. K Kaushansky
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Kaushansky, K. Small molecule mimics of hematopoietic growth factors: improving on Mother Nature?. Leukemia 15, 673–674 (2001). https://doi.org/10.1038/sj.leu.2402058

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