| Size | Price | |
|---|---|---|
| 100mg | ||
| 250mg | ||
| 500mg | ||
| Other Sizes |
| Targets |
0.79 µM (ASH1L histone methyltransferase)[1]
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|---|---|
| ln Vitro |
AS-99 is examined in relation to a panel of 20 histone methyltransferases, which comprises SETD2, NSD1, NSD2, and NSD3. For all studied histone methyltransferases, NO substantial inhibition is seen at 50 µM of AS-99, suggesting > 100-fold selectivity towards ASH1L[1]. AS-99 exhibits negligible or no effects at 10 µM or greater doses on the proliferation of leukemia cells without MLL1 translocations, such as SET2 and K562[1]. Quantification of Annexin V positive cells[1] indicates that AS-99 (1 -8 µM; 7 days) similarly promotes apoptosis in MLL leukemia cells, but not in K562 cells. Transcriptional programs driven by MLL fusion are suppressed by AS-99[1].Comparing AS-99-treated cells to DMSO-treated cells, less H3K36me2 peaks are observed[1].
|
| ln Vivo |
In mice, leukemia burden is decreased by AS-99 (30 mg/kg; ip; qd, administered for 14 consecutive days)[1]. The in vivo investigations conducted on mice using AS-99 show that the drug has an acceptable half-life (~5–6 h), a favorable exposure in plasma upon iv and ip injection (AUC = 9701 hr* ng/mL and 10,699 hr* ng/mL, respectively), and a Cmax >10 µM[1].
|
| 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: diminished 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.
|
| Molecular Formula |
C27H30F3N5O3S2
|
|---|---|
| Molecular Weight |
593.68
|
| CAS # |
2323623-93-2
|
| Related CAS # |
AS-99 TFA;AS-99
|
| SMILES |
N1(C)CC(C(NCC2=CC3=C(C=C2)C(C2=CC=CC(C(N)=S)=C2)=CN3C2CCN(S(C(F)(F)F)(=O)=O)CC2)=O)C1
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
|---|
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6844 mL | 8.4220 mL | 16.8441 mL | |
| 5 mM | 0.3369 mL | 1.6844 mL | 3.3688 mL | |
| 10 mM | 0.1684 mL | 0.8422 mL | 1.6844 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.
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