The progenitor of these compounds was hexamethylene bisacetamide, a drug that is able to induce remission in patients with myelodysplastic syndrome and acute myeloid leukemia, but cannot be used in clinical trials for the high dosage required and adverse side effects.
In the absence of induction of precocious differentiation, any compound promoting progenitor cell proliferation would result simply in more progenitors, not more β cells.
Against the leukemia progenitor cell line KG1a, triazole compounds 15a and 15d 15f and oxadiazole compounds 24a 24d were more potent than dasatinib.
Similar to pleomorphic clusters, columnar cells in early tumor foci from compound mice expressed progenitor cell markers (Figure S5A).
Such SVZ aplasia could either be the result of an exhaustion of the pool of SVZ progenitors due to chronic demyelination, and/or may reflect a direct toxic effect of the compound on SVZ progenitors, both possibilities being non-mutually exclusive.
A comparison of these compounds with their progenitor tropanes cast into doubt the existence of proximal binding sites on the DAT, and offered support for the existence of different binding sites for the 8-azatropanes compared with 8-oxa- and 8-thiatropanes.
It is possible that Lead I compounds stimulated endocrine progenitor proliferation as well, further experimentation will be required to test this.
Each member of this class of compounds shares a common progenitor in the cation olefin reaction (COR), the C C bond forming workhorse of terpene biosynthesis.
Further treatment with soluble growth factors and small molecules, such as A83-01 and Compound E, these induced endodermal progenitor cells efficiently differentiated into functional hepatocytes.
Expression of progenitor cell markers in tumor foci of compound mice also differ in Id2 expression at late tumor stages when positive cells were very rare (Figure S5B).
