| Size | Price | Stock | Qty |
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| Targets |
AS-85 targets ASH1L (Absent, Small, or Homeotic-like 1), a histone methyltransferase that catalyzes the methylation of histone H3 at lysine 36 (H3K36). The compound inhibits ASH1L with an IC50 of 0.6 μM and binds to the ASH1L SET domain with a KD of 0.78 μM. ASH1L is a component of the COMPASS-like complex and is involved in epigenetic regulation of gene expression. Dysregulation of ASH1L has been implicated in various cancers, including leukemias with MLL1 translocations. By inhibiting ASH1L, AS-85 reduces H3K36 methylation and alters gene expression programs that drive cancer cell proliferation and survival.
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| ln Vitro |
AS-85 has no effect on K562 leukemia cells without MLL1 translocations and inhibits the proliferation of leukemia cells (MV4;11, MOLM13, and KOPN8) containing various MLL1 translocations, with GI50 values ranging from 5 µM to 25 µM[1].
AS-85 demonstrates potent in vitro anti-leukemic activity. The compound inhibits the growth of leukemia cells harboring different MLL1 translocations, including MV4;11, MOLM13, and KOPN8 cells, with GI50 (50% growth inhibition) values ranging from 5 μM to 25 μM. AS-85 strongly binds to the ASH1L SET domain with a KD of 0.78 μM. The compound’s anti-leukemic activity is attributed to its inhibition of ASH1L histone methyltransferase activity, which leads to changes in gene expression that reduce cancer cell proliferation and survival. |
| ln Vivo |
No detailed in vivo activity data for AS-85 has been published in the available literature. The compound has been primarily characterized in vitro as a tool for studying ASH1L and leukemia. Further studies would be needed to evaluate the efficacy of AS-85 in animal models of leukemia or other cancers. The compound’s cell-permeable nature and favorable physicochemical properties suggest that it could have in vivo activity.
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| Enzyme Assay |
The binding of AS-85 to the ASH1L SET domain can be assessed using surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC). In a typical SPR assay, recombinant ASH1L SET domain protein is immobilized on a sensor chip, and varying concentrations of AS-85 are injected over the surface. The association rate (ka), dissociation rate (kd), and equilibrium dissociation constant (KD) are calculated from the sensorgram data using a 1:1 Langmuir binding model. The KD for AS-85 binding to the ASH1L SET domain is 0.78 μM. The inhibitory activity of AS-85 against ASH1L can be assessed using in vitro histone methyltransferase assays.
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| Cell Assay |
The cellular activity of AS-85 is assessed using leukemia cell lines harboring MLL1 translocations, including MV4;11, MOLM13, and KOPN8 cells. Cells are seeded in 96-well plates and treated with escalating concentrations of AS-85 for 72 hours. Cell viability is measured using MTT or CellTiter-Glo assays, and the GI50 (50% growth inhibition) values are calculated from dose-response curves. The effects of AS-85 on histone H3K36 methylation are assessed by Western blotting using antibodies specific for H3K36me2 or H3K36me3. The effects of AS-85 on gene expression are assessed by RNA sequencing or quantitative PCR.
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| Animal Protocol |
No detailed in vivo animal model data for AS-85 has been published in the available literature. As a research compound, AS-85 has not been evaluated in animal models to assess its in vivo efficacy or pharmacokinetic properties. Future studies may involve the use of mouse xenograft models of leukemia to assess the antitumor activity of AS-85. The compound’s cell-permeable nature and favorable physicochemical properties suggest that it could have in vivo activity.
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| ADME/Pharmacokinetics |
No detailed pharmacokinetic data for AS-85 has been published in the available literature. The compound is described as cell-permeable with increased cLogP and decreased tPSA, suggesting that it has favorable drug-like properties. Further studies would be needed to characterize the absorption, distribution, metabolism, and excretion (ADME) properties of AS-85, including oral bioavailability, plasma protein binding, clearance, half-life, and tissue distribution.
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| Toxicity/Toxicokinetics |
No detailed toxicity data for AS-85 has been published in the available literature. As a research compound, AS-85 has not been subjected to comprehensive toxicology studies. The mechanism of action, which involves the inhibition of ASH1L histone methyltransferase, could have off-target effects on gene expression in normal cells. Further studies would be needed to assess the safety profile of AS-85.
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| References | |
| Additional Infomation |
AS-85 is a potent inhibitor of the ASH1L histone methyltransferase, with an IC50 of 0.6 μM and a KD of 0.78 μM for the ASH1L SET domain. The compound demonstrates significant anti-leukemic activity, inhibiting the growth of leukemia cells harboring MLL1 translocations with GI50 values ranging from 5 μM to 25 μM. AS-85 is a cell-permeable compound with favorable physicochemical properties. The compound is a valuable research tool for studying the role of ASH1L in cancer and for exploring potential therapeutic strategies for leukemia.
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| Molecular Formula |
C26H28F3N5O3S2
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| Molecular Weight |
579.66
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| Exact Mass |
579.158
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| CAS # |
2323623-80-7
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| PubChem CID |
138608677
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
2.5
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
39
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| Complexity |
1010
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N1CC(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
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| InChi Key |
WDQKQCWRQIVDBA-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H28F3N5O3S2/c27-26(28,29)39(36,37)33-8-6-20(7-9-33)34-15-22(17-2-1-3-18(11-17)24(30)38)21-5-4-16(10-23(21)34)12-32-25(35)19-13-31-14-19/h1-5,10-11,15,19-20,31H,6-9,12-14H2,(H2,30,38)(H,32,35)
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| Chemical Name |
N-[[3-(3-carbamothioylphenyl)-1-[1-(trifluoromethylsulfonyl)piperidin-4-yl]indol-6-yl]methyl]azetidine-3-carboxamide
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : 100 mg/mL (172.51 mM)
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| 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 | 1.7251 mL | 8.6257 mL | 17.2515 mL | |
| 5 mM | 0.3450 mL | 1.7251 mL | 3.4503 mL | |
| 10 mM | 0.1725 mL | 0.8626 mL | 1.7251 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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