AI-10-49

AI-10-49
Identifiers
  • 2,2'-(5,5'-((Oxybis(ethane-2,1-diyl))bis(oxy))bis(pyridine-5,2-diyl))bis(5-(trifluoromethoxy)-1H-benzo[d]imidazole)
CAS Number
ChemSpider
UNII
Chemical and physical data
FormulaC30H22F6N6O5
Molar mass660.533 g·mol−1
3D model (JSmol)
  • FC(F)(F)OC1=CC2=C(C=C1)NC(C(C=C3)=NC=C3OCCOCCOC(C=C4)=CN=C4C5=NC6=CC(OC(F)(F)F)=CC=C6N5)=N2
  • InChI=1S/C30H22F6N6O5/c31-29(32,33)46-17-1-5-21-25(13-17)41-27(39-21)23-7-3-19(15-37-23)44-11-9-43-10-12-45-20-4-8-24(38-16-20)28-40-22-6-2-18(14-26(22)42-28)47-30(34,35)36/h1-8,13-16H,9-12H2,(H,39,41)(H,40,42)
  • Key:WJBSSBFGPKTMQQ-UHFFFAOYSA-N

AI-10-49 is a small molecule inhibitor of leukemic oncoprotein CBFβ-SMHHC developed by the laboratory of John Bushweller (University of Virginia) with efficacy demonstrated by the laboratories of Lucio H. Castilla (University of Massachusetts Medical School) and Monica Guzman (Cornell University).[1][2][3][4] AI-10-49 allosterically binds to CBFβ-SMMHC and disrupts protein-protein interaction between CBFβ-SMMHC and tumor suppressor RUNX1. This inhibitor is under development as an anti-leukemic drug.

  1. ^ Illendula A, Pulikkan JA, Zong H, Grembecka J, Xue L, Sen S, et al. (February 2015). "Chemical biology. A small-molecule inhibitor of the aberrant transcription factor CBFβ-SMMHC delays leukemia in mice". Science. 347 (6223): 779–784. doi:10.1126/science.aaa0314. PMC 4423805. PMID 25678665.
  2. ^ Chen A, Koehler AN (February 2015). "Drug discovery. Tying up a transcription factor". Science. 347 (6223). New York, N.Y.: 713–4. doi:10.1126/science.aaa6119. PMID 25678644. S2CID 20025135.
  3. ^ Miura G (April 2015). "Free RUNX1". Nature Chemical Biology. 11 (4): 241. doi:10.1038/nchembio.1784.
  4. ^ Pulikkan JA, Illendula A, Grembecka J, Xue L, Rajewski R, Guzman ML, et al. (November 2014). "Selective inhibition of the leukemia fusion protein CBFβ-SMMHC by small molecule AI-10-49 in the treatment of Inv (16) AML". Blood. 124 (21): 390. doi:10.1182/blood.V124.21.390.390.