Method for producing highly functional platelets
AssigneesKyoto University, Megakaryon Corporation
InventorsKoji Eto, Sou Nakamura, Yukitaka Ito, Tomohiro Shigemori, Takeaki Dohda
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Abstract
The present invention provides a highly functional platelet production promoting agent which comprises one or a plurality of aryl hydrocarbon receptor (AhR) antagonists and one or a plurality of Rho-associated coiled-coil forming kinase (ROCK) inhibitors.
Claims20
A platelet production promoting agent which comprises one or a plurality of aryl hydrocarbon receptor (AhR) antagonists selected from the group consisting of 4-(2-(2-(benzo[b]thiophen-3-yl)-9-isopropyl-9H-purin-6-ylamino)ethyl)phenol (SR-1), 2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazo-phenyl)-amide (CH-223191), and N-]2-(3H-indol-3-yl)ethyl]-9-isopropyl-2-(5-methyl-3-pyridyl)purin-6-amine (GNF-351), and one or a plurality of Rho-associated coiled-coil forming kinase (ROCK) inhibitors selected from the group consisting of Y27632 and Y39983.
A platelet production method, which comprises
- bringing a platelet production promoting agent comprising (a) one or a plurality of aryl hydrocarbon receptor (AhR) antagonists and (b) one or a plurality of Rho-associated coiled-coil forming kinase (ROCK) inhibitors selected from the group consisting of Y27632, Y39983, SLX-2119, RKI-1447, azaindole1, SR-3677, and Staurosporine into contact with megakaryocytes or progenitor cells thereof, and
- suppressing the expression or function of high mobility group At-hook (HMGA) proteins in the megakaryocytes or progenitor cells thereof by siRNA or miRNA that directly or indirectly suppresses expression of HMGA gene.
A composition, which comprises
- (a) 200 nM to less than 1000 nM of 4-(2-(2-(benzo[b]thiophen-3-yl)-9-isopropyl-9H-purin-6-ylamino)ethyl)phenol (SR-1),
- 0.2 μM to less than 4 μM of 2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazo-phenyl)-amide (CH-223191), or
- 20 nM to less than 300 nM of N42-(3H-indol-3-yl)ethyl]-9-isopropyl-2-(5-methyl-3-pyridyl)purin-6-amine (GNF-351);
- and
- (b) one or a plurality of Rho-associated coiled-coil forming kinase (ROCK) inhibitors selected from the group consisting of Y27632, Y39983, SLX-2119, RKI-1447, azaindole1, SR-3677, and Staurosporine.
Dependencies are inferred from the claim text.