AS-99 free base 

AS-99 is a first-in-class, potent and selective ASH1L histone methyltransferase inhibitor (IC₅₀= 0.79 µM, K_d= 0.89 µM) with anti-leukemic activity. AS-99 blocks cell proliferation, induces apoptosis and differentiation, downregulates MLL fusion target genes, and reduces the leukemia burden in vivo^[1].

AS-99 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 on any of the tested histone methyltransferases, indicating over 100-fold selectivity towards ASH1L^[1].
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^[1].
AS-99 (1-8 µM; 7 days) 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^[1].
AS-99 suppresses MLL fusion driven transcriptional programs^[1].
AS-99 results in a reduced number of H3K36me2 peaks when compared to the DMSO-treated cells^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

AS-99 (30 mg/kg; i.p.; q.d., treated for 14 consecutive days) reduces leukemia burden in mice^[1].
AS-99 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^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

593.68

C₂₇H₃₀F₃N₅O₃S₂

2323623-93-2

Solid

White to off-white

O=C(C1CN(C)C1)NCC2=CC3=C(C=C2)C(C4=CC=CC(C(N)=S)=C4)=CN3C5CCN(S(=O)(C(F)(F)F)=O)CC5

Room temperature in continental US; may vary elsewhere.

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

• [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.  [Content Brief]