دورية
BB-10010: An Active Variant of Human Macrophage Inflammatory Protein-1αWith Improved Pharmaceutical Properties
| العنوان: | BB-10010: An Active Variant of Human Macrophage Inflammatory Protein-1αWith Improved Pharmaceutical Properties |
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| المؤلفون: | Hunter, M.G., Bawden, L., Brotherton, D., Craig, S., Cribbes, S., Czaplewski, L.G., Dexter, T.M., Drummond, A.H., Gearing, A.H., Heyworth, C.M., Lord, B.I., McCourt, M., Varley, P.G., Wood, L.M., Edwards, R.M., Lewis, P.J. |
| المصدر: | Blood; December 1995, Vol. 86 Issue: 12 p4400-4408, 9p |
| مستخلص: | The stem cell inhibitor, macrophage inflammatory protein-1α(MIP-1α) or LD78, protects multipotent hematopoietic progenitors in murine models from the cytotoxic effects of chemotherapy. Clinical use of human MIP-1αduring chemotherapy could therefore lead to faster hematologic recovery and may allow dose intensification. We have also shown that human MIP-1αcauses the rapid mobilization of hematopoietic cells, suggesting an additional clinical use in peripheral blood stem cell transplantation. However, the clinical evaluation of human MIP-1αis complicated by its tendency to associate and form high molecular weight polymers. We have produced a variant of rhMIP-1α, BB-10010, carrying a single amino acid substitution of Asp26 > Ala, with a reduced tendency to form large polymers at physiologic pH and ionic strength. This greatly increases its solubility, facilitating its production and clinical formulation. We confirmed the potency of BB-10010 as a human MIP-1α-like agonist in receptor binding, calcium mobilization, inhibition of colony formation, and thymidine suicide assays. The myeloprotective activity of BB-10010 was shown in a murine model of repeated chemotherapy using hydroxyurea. BB-10010 is therefore an ideal variant with which to evaluate the therapeutic potential of recombinant human MIP-1α. |
| قاعدة البيانات: | Supplemental Index |
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