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ABSTRACT
Introduction: There is an unmet need of strategies for ex-vivo expansion of hematopoetic stem cells (HSCs) without loss of their primitive nature or stemness. We evaluate here a patent that attempts to address this need via key small molecules 1 and 40 that possess a pyrimido[4,5-b]indole core.
Areas covered: (i) Discussion on literature reports of diverse strategies for ex-vivo expansion of stem cells. (ii) Synthetic scheme to 1, and general synthetic schemes for compounds 1-55 reported in the patent application. (iii) Analysis of the in vitro biological data for 1 and 40. Highlight here is: 1 and 40 when used in combination with StemReginin1 (SR1), an established aryl hydrocarbon receptor antagonist known for ex-vivo HSC expansion, demonstrate better HSC expansion relative to SR1 alone. (iv) Analysis of the in vivo biological data for 1 and 40.
Expert opinion: Compelling evidence on the molecular mechanism of action of 1 and 40 is not provided making it difficult to optimize this series. It is suggested here that combining these molecules with homing molecules will possibly improve overall engraftment time and hematopoietic recovery. The numerous literature reports and biological data indicates that these pyrimido[4,5-b]indole derivatives are promising candidates for the development of potential therapies for hematopoietic ailments.
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.