Selective ASH1L histone methyltransferase inhibitor
AS 99 is a selective ASH1L histone methyltransferase inhibitor (IC50 = 0.79 μM); it binds to the autoinhibitory loop region in the SET domain (Kd = 0.89 μM). AS 99 exhibits >100-fold selectivity for ASH1L over a range of lysine methyltransferases; no significant inhibition is observed at 50 μM against a panel of 20 histone methyltransferases, including NSD1, NSD2, NSD3, and SETD2. In leukemia cells, AS 99 blocks H3K36 methylation, and causes a dose-dependent downregulation of MLL fusion target genes; it also induces apoptosis and differentiation and inhibits cell proliferation. AS 99 reduces leukemia burden in the xenotransplantation mouse model of MLL leukemia without affecting blood count in normal mice.
| Marque | Tocris Bioscience |
|---|---|
| Réf. B-LABO | BL-RE-125275 |
| Réf. fabricant | 18765955 |
| Nom chimique ou matériau | N-[[3-[3-(Aminothioxomethyl)phenyl]-1-[1-[(trifluoromethyl)sulfonyl]-4-piperidinyl]-1 H-indol-6-yl]methyl]-1-methyl-3-azetidinecarboxamide |
| CAS | 2323623-93-2 |
| Quantité | 5 mg |
| Cible | Lysine Methyltransferase Inhibitors |
| Formule moléculaire | C<sub>27</sub>H<sub>30</sub>F<sub>3</sub>N<sub>5</sub>O<sub>3</sub>S<sub>2</sub> |
| Pureté | 0.98 |
