BTB-1 | Mitotic kinesin Kif18A inhibitor

BTB-1 (86030-08-2) is a  selective, ATP-competitive and reversible inhibitor of mitotic kinesin Kif18A, IC₅₀=1.7 mM.^1,2 Binds to an allosteric site near Kif18A loop 5 preventing a range of conformational changes thereby blocking motor function.³ Inhibits the differentiation of mouse bone marrow cells to dendritic cells.⁴ Suppresses the replication of influenza A virus, inhibiting activation of AKT, p38 MAPK, SAPK and RanBP3 leading to the prevention of nuclear export of viral ribonucleoprotein complexes. Greatly improves the viability of IAV-infected mice.⁵

References/Citations:

1. Catarinella et al. (2009), BTB-1; a small molecule inhibitor of the mitotic motor protein Kif18A; Chem. Int. Ed. Engl., 48 9072
2. Braun et al. (2015), Synthesis and biological evaluation of optimized inhibitors of the mitotic kinesin Kif18A; ACS Chem. Biol., 10 554
3. Locke et al. (2017), Structural basis of human kinesin-8 function and inhibition; Proc. Natl. Acad. Sci. USA, 114 E9539
4. Kim et al. (2020), Kinesin family member KIF18A is a critical cellular factor that regulates the differentiation and activation of dendritic cells; Genes Genomics, 42 41
5. Cho et al. (2020), Selective and ATP-competitive kinesin KIF18A inhibitor suppresses the replication of influenza A virus; J. Cell Mol. Med., 24 5463