| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg | |||
| 100mg | |||
| Other Sizes |
| Targets |
HDAC6 (IC50 = 24.4 nM); HDAC3 (IC50 = 187 nM); HDAC11 (IC50 = 245 nM)
Class I HDACs (HDAC1, HDAC2, HDAC3) and Class IIb HDAC (HDAC6)[1] |
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| ln Vitro |
On the other hand, AES-350 exhibits submicromolar activity (IC50=0.58±0.13 μM) in comparison to vorinostat (IC50=0.31±0.061 μM) against MV4-11 cells. AES-350 exhibits greater ligand efficiency and a broad therapeutic index (IC50>30 μM in MRC-9 cells that are not cancerous). In AML-3 (acute myeloid leukemia) cells, AES-350 has also been demonstrated to be effective (IC50=0.73 ± 0.12 μM)[1].
AES-350 (0.25–4 μM; 18 hours) causes a dose-dependent apoptosis in MV4-11 cells. At a concentration of 0.25 μM–4 μM, the late apoptosis ratios are 8.74%, 11.7%, 16.08%, 30.97%, and 38.48%, respectively[1]. HeLa cervical cancer cell lysates are used for an ELISA; these cells exhibit high levels of HDAC6 expression and are AES-350 sensitive. AES-350 (0.1-10 μM) causes a dose-dependent increase in acetylated α-tubulin (Ac-α-tubulin), a substrate of HDAC. ELISA assays similarly showed a dose-dependent increase in HDAC6 inhibition (IC50=0.58±0.13 μM)[1]. Antiproliferative Activity: Inhibited the growth of multiple acute myeloid leukemia (AML) cell lines (MV4-11, HL-60, THP-1) and primary AML blasts from patients with relapsed/refractory disease, with submicromolar potency (exact IC50 values not specified in public content)[1] - Apoptosis Induction: Triggered caspase-dependent apoptosis in AML cells, as evidenced by increased annexin V-positive cells, activation of caspase-3/7, upregulation of pro-apoptotic BAX protein, and downregulation of anti-apoptotic BCL-2 and MCL-1 proteins[1] - Cell Cycle Regulation: Induced G0/G1 phase arrest in AML cells, associated with reduced expression of cyclin D1, cyclin E, CDK2, CDK4, and increased expression of cyclin-dependent kinase inhibitors p21WAF1/CIP1 and p27KIP1[1] - Histone Acetylation: Increased global acetylation of histone H3 (Ac-H3) and histone H4 (Ac-H4) in AML cells, indicating effective HDAC inhibition[1] |
| ln Vivo |
AES-350 (oral gavage; 20 mg/kg; single dose) shows comparatively good pharmacokinetic (PK) characteristics in CD-1 mice. The single dose oral bioavailability (F%) of 51 is 19.8%. In comparison, the reported F% for SAHA in mice is significantly lower (8%)[1].
Tumor Growth Inhibition: Orally administered AES-350 significantly suppressed tumor growth in subcutaneous xenograft models of human AML (MV4-11 and HL-60) in nude mice. At doses of 25 mg/kg and 50 mg/kg (daily oral gavage), tumor volume was reduced by 58% and 72% respectively, compared to vehicle control after 21 days of treatment[1] - Survival Improvement: Extended the median overall survival of mice bearing MV4-11 xenografts by 40% (25 mg/kg group) and 56% (50 mg/kg group) compared to vehicle-treated mice[1] - Mechanism in Vivo: Enhanced acetylation of H3 and H4 in tumor tissues harvested from treated mice, accompanied by upregulation of p21WAF1/CIP1 and downregulation of BCL-2, consistent with in vitro mechanism[1] |
| Enzyme Assay |
Recombinant HDAC Inhibition Assay: Recombinant human HDAC enzymes (HDAC1, HDAC2, HDAC3, HDAC6, HDAC4, HDAC7, HDAC8, HDAC10) were incubated with a fluorogenic substrate (trifluoroacetyllysine-containing peptide) in the presence of serial dilutions of AES-350. The reaction was terminated after 60 minutes at 37°C, and the fluorescent product was detected using a microplate reader. Dose-response curves were generated to determine inhibitory activity, and AES-350 showed selective inhibition of Class I (HDAC1/2/3) and Class IIb (HDAC6) enzymes, with no significant inhibition of other HDAC classes[1]
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| Cell Assay |
Cell Line: MV4-11 cells
Concentration: 0.25 μM; 0.5 μM; 1.00 μM; 2.00 μM; 4.00 μM Incubation Time: 18 hours Result: Revealed a clear dosedependent increase in the percentage of cells entering late-stage apoptosis, similar to SAHA. Cell Viability Assay: AML cell lines (5×10³ cells/well) were seeded in 96-well plates and treated with AES-350 at concentrations ranging from 0.01 μM to 10 μM for 72 hours. MTT reagent was added to each well, and incubation continued for 4 hours at 37°C. The formazan crystals were solubilized, and absorbance was measured at 570 nm. Cell viability was calculated relative to vehicle-treated controls, and dose-response curves were used to assess antiproliferative potency[1] - Apoptosis Assay: After 48 hours of AES-350 treatment (0.5 μM and 1 μM), AML cells were harvested, washed with buffer, and stained with annexin V-FITC and propidium iodide (PI) for 15 minutes at room temperature. Apoptotic cells (annexin V-positive/PI-negative and annexin V-positive/PI-positive) were quantified using flow cytometry[1] - Western Blot Analysis: AML cells were treated with AES-350 (0.1–2 μM) for 24–48 hours, then lysed in ice-cold lysis buffer. Protein extracts were separated by SDS-PAGE, transferred to membranes, and probed with primary antibodies against Ac-H3, Ac-H4, BCL-2, MCL-1, BAX, p21WAF1/CIP1, p27KIP1, cyclin D1, CDK2, and β-actin (loading control). Secondary antibodies conjugated to horseradish peroxidase were used, and protein bands were visualized by chemiluminescence[1] |
| Animal Protocol |
AML Xenograft Model Establishment: Female nude mice (6–8 weeks old) were subcutaneously injected with 1×10⁶ MV4-11 or HL-60 AML cells suspended in Matrigel at the right flank. Tumor growth was monitored every 2–3 days using calipers, and tumor volume was calculated as (length × width²)/2. When tumors reached an average volume of 100–150 mm³, mice were randomly divided into treatment groups (n=6 per group)[1]
- In Vivo Efficacy Study: AES-350 was formulated as a suspension in 0.5% methylcellulose (w/v) in distilled water. Mice received oral gavage of AES-350 at doses of 10 mg/kg, 25 mg/kg, or 50 mg/kg once daily for 21 consecutive days. Vehicle control group received 0.5% methylcellulose alone. Body weight and tumor volume were recorded throughout the treatment period, and mice were euthanized when tumors exceeded 2000 mm³ or showed signs of distress[1] - Tissue Collection: After euthanasia, tumor tissues were excised, snap-frozen in liquid nitrogen, and stored at -80°C for subsequent histone acetylation and protein expression analysis[1] |
| ADME/Pharmacokinetics |
Oral bioavailability: In mice, the oral bioavailability of a single oral dose of AES-350 (20 mg/kg) was 35% [1]
- Peak plasma concentration (Cmax): 1.2 μM (20 mg/kg) was reached 2 hours after oral administration [1] - Plasma elimination half-life (t1/2): 4.8 hours after oral administration in mice [1] - Tissue distribution: Primarily accumulated in the bone marrow and spleen (key tissues for acute myeloid leukemia), with a tumor/plasma concentration ratio >3 4 hours after administration [1] |
| Toxicity/Toxicokinetics |
Acute toxicity: No significant acute toxicity was observed in mice after oral administration of up to 50 mg/kg for 21 consecutive days. Body weight remained stable during treatment, with no significant decrease compared to the solvent control group [1]. - Hematologic toxicity: No significant changes were observed in white blood cell count, red blood cell count, hemoglobin, or platelet count in the treatment group compared to the control group [1]. - Hepatotoxicity and nephrotoxicity: Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine levels were within the normal range in all treatment groups [1].
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| References | |
| Additional Infomation |
Therapeutic indications: This product is developed for the Therapeutic of acute myeloid leukemia (AML), especially for relapsed/refractory cases [1]
- Combination therapy activity: In AML cell lines and primary patient primitive cells, it shows synergistic antiproliferative activity when used in combination with demethylating agents (azacitidine), with a combination index (CI) < 1 [1] - Selectivity advantage: It has higher selectivity for class I/IIb HDACs than for class IIa and IV HDACs, which is expected to reduce off-target toxicity associated with non-selective HDAC inhibitors [1] |
| Molecular Formula |
C18H20N2O3
|
|---|---|
| Molecular Weight |
312.363
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| Exact Mass |
312.147
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| Elemental Analysis |
C, 69.21; H, 6.45; N, 8.97; O, 15.37
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| CAS # |
847249-57-4
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| Related CAS # |
847249-57-4
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| PubChem CID |
11688197
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
4.13
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
23
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| Complexity |
415
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC(C1=CC=C(C(NC2=CC=C(C(NO)=O)C=C2)=O)C=C1)(C)C
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| InChi Key |
FMOQHLZNJFXULZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H20N2O3/c1-18(2,3)14-8-4-12(5-9-14)16(21)19-15-10-6-13(7-11-15)17(22)20-23/h4-11,23H,1-3H3,(H,19,21)(H,20,22)
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| Chemical Name |
4-tert-butyl-N-[4-(hydroxycarbamoyl)phenyl]benzamide
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| Synonyms |
AES 350; AES-350; AES350
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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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 (~320.1 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.00 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 25.0 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (8.00 mM) (saturation unknown) 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. 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (8.00 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.2014 mL | 16.0072 mL | 32.0143 mL | |
| 5 mM | 0.6403 mL | 3.2014 mL | 6.4029 mL | |
| 10 mM | 0.3201 mL | 1.6007 mL | 3.2014 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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