Size | Price | Stock | Qty |
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1mg |
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5mg |
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Other Sizes |
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Targets |
0.79 µM (ASH1L histone methyltransferase)[1]
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ln Vitro |
AS-99 TFA is measured against a panel comprising NSD1, NSD2, NSD3, and SETD2, among other 20 histone methyltransferases. At 50 µM of AS-99 TFA, no discernible inhibition is seen on any of the examined histone methyltransferases, suggesting a selectivity of over 100 times for ASH1L[1]. At 10 µM and greater concentrations, AS-99 exhibits little or very little influence on the growth of leukemia cells without MLL1 translocations, such as SET2 and K562[1]. (1–8 µM; 7 days) According to the quantification of Annexin V positive cells, TFA also causes apoptosis in MLL leukemia cells but not in K562 cells[1]. MLL fusion-driven transcriptional pathways are suppressed by AS-99 TFA[1]. Compared to the cells treated with DMSO, AS-99 produces less H3K36me2 peaks[1].
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ln Vivo |
In mice, leukemia burden is decreased by AS-99 (30 mg/kg; ip; qd, administered for 14 consecutive days) TFA[1]. When administered intravenously (IV) and intraperitoneally (IP) to mice, AS-99 TFA exhibits good exposure in plasma (AUC = 9701 hr* ng/mL and 10,699 hr* ng/mL, respectively), a reasonable half-life (~5–6 h), and a Cmax >10 µM[1].
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Cell Assay |
RT-PCR[1]
Cell Types: MOLM13 cells Tested Concentrations: 2-6 µM Incubation Duration: 7 days Experimental Results: Led to a dose-dependent downregulation of canonical MLL fusion target genes required for leukemogenesis including MEF2C, DLX2, FLT3, and HOXA9. |
Animal Protocol |
Animal/Disease Models: 8- to 10 -week old female NSG mice (bearing MV4;11 cells)[1]
Doses: 30 mg/kg Route of Administration: Ip; qd, treated for 14 days Experimental Results: decreased the leukemia burden in the xenotransplantation mouse model of MLL leukemia without affecting blood counts in normal mice. |
References |
[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.
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Molecular Formula |
C29H31F6N5O5S2
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Molecular Weight |
707.71
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Related CAS # |
AS-99 free base;2323623-93-2;AS-99
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
Solubility (In Vitro) |
DMSO :~100 mg/mL (~141.30 mM)
H2O :~12.5 mg/mL (~17.66 mM) |
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Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (3.53 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (2.94 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.  (Please use freshly prepared in vivo formulations for optimal results.) |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 1.4130 mL | 7.0650 mL | 14.1301 mL | |
5 mM | 0.2826 mL | 1.4130 mL | 2.8260 mL | |
10 mM | 0.1413 mL | 0.7065 mL | 1.4130 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.