AS-99 TFA 是首创的、有效的、选择性的 ASH1L 组蛋白甲基转移酶抑制剂 (IC₅₀= 0.79 µM, K_d= 0.89 µM)，具有抗白血病活性。AS-99 TFA 在体内阻断细胞增殖，诱导细胞凋亡 (apoptosis) 和分化，下调 MLL 融合靶基因，减轻白血病。

AS-99 TFA is a first-in-class, potent and selective ASH1L histone methyltransferase inhibitor (IC 50 =?0.79?μM, K d =?0.89?μM) with anti-leukemic activity. AS-99 TFA blocks cell proliferation, induces apoptosis and differentiation, downregulates MLL fusion target genes, and reduces the leukemia burden in vivo.

Solid

0.79?μM (ASH1L histone methyltransferase)

AS-99 TFA is tested against a panel of 20 histone methyltransferases, including NSD1, NSD2, NSD3, and SETD2. NO significant inhibition is observed at 50?μM of AS-99 TFA on any of the tested histone methyltransferases, indicating over 100-fold selectivity towards ASH1L.
AS-99 shows a several fold weaker effect on the proliferation of leukemia cells without MLL1 translocations, such as SET2 and K562, with no or limited effects at 10?μM or higher concentrations.
AS-99 (1-8 μM; 7 days) TFA also induces apoptosis in the MLL leukemia cells, but not in the K562 cells, as assessed by the quantification of the Annexin V positive cells.
AS-99 TFA suppresses MLL fusion driven transcriptional programs.
AS-99 results in a reduced number of H3K36me2 peaks when compared to the DMSO-treated cells.

AS-99 (30?mg/kg; i.p.; q.d., treated for 14 consecutive days) TFA reduces leukemia burden in mice.
AS-99 TFA is used for in vivo studies in mice, which reveals favorable exposure in plasma upon i.v. and i.p. administration (AUC?=?9701?hr* ng/mL and 10,699?hr* ng/mL, respectively), suitable half-life (~5–6?h) and Cmax?>10?μM. has not independently confirmed the accuracy of these methods. They are for reference only.

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moistur In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

[1]. David S. Rogawski, Jing Deng, Hao Li, Tomasz Cierpicki, Jolanta Grembecka, et al. Discovery of first-in-class inhibitors of ASH1L histone methyltransferase with anti-leukemic activity. Nat Commun. 2021 May 14;12(1):2792.

In Vitro: DMSO : 100 mg/mL (141.30 mM; Need ultrasonic)H₂O : 12.5 mg/mL (17.66 mM; Need ultrasonic)配制储备液