425388-80-3Relevant academic research and scientific papers
DISLODGEMENT AND RELEASE OF HSC USING ALPHA 9 INTEGRIN ANTAGONIST AND CXCR4 ANTAGONIST
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, (2016/07/05)
Haematopoietic stem cell mobilization is a process whereby haematopoietic stem cells are stimulated out of the bone marrow space. Before HSC can mobilize, they must be dislodged and released from the BM stem cell niche in which they reside and are retained by adhesive interactions. Accordingly, in an aspect of the present invention there is provided a method for enhancing dislodgement of HSC and their precursors and progenitors thereof from a BM stem cell binding ligand in vivo or ex vivo, said method comprising administering in vivo or ex vivo an effective amount of an antagonist of an α9 integrin or an active portion thereof and a CXCR4 antagonist or an active portion thereof to the BM stem cell niche. Once mobilized to the peripheral blood (PB) the HSC may be collected for transplant. Methods which enhance mobilization of the HSC can also improve treatments of haematological disorders.
The discovery of small molecule carbamates as potent dual α4β1/α4β7 integrin antagonists
Chang, Linda L.,Truong, Quang,Mumford, Richard A.,Egger, Linda A.,Kidambi, Usha,Lyons, Kathryn,McCauley, Ermengilda,Van Riper, Gail,Vincent, Stella,Schmidt, John A.,MacCoss, Malcolm,Hagmann, William K.
, p. 159 - 163 (2007/10/03)
The α4β1 and α4β7 integrins are implicated in several inflammatory disease states. Systematic SAR studies of an α4β1-specific arylsulfonyl-Pro-Tyr lead led to the identification of a new α4β7 binding site, best captured by O-carbamates of Tyr for this structural class. Several compounds showed a 200- to 400-fold improvement in α4β7 binding affinity while maintaining subnanomolar α4β1 activity, for example 2l, VCAM-Ig α4β1 IC50=0.13 nM, VCAM-Ig α4β7 IC50=1.92 nM.
