| Size | Price | Stock | Qty |
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| 100mg |
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| Other Sizes |
| Targets |
HSP90; HSV-1; ERK1; ERK2; NF-κB; Akt; HIF-1α; VEGF/VEGFR-2
AT-533 targets two distinct biological entities: heat shock protein 90 (Hsp90) and herpes simplex virus (HSV). Hsp90 is a molecular chaperone that is essential for the proper folding and function of many proteins, including those involved in cell signaling, proliferation, and survival. By inhibiting Hsp90, AT-533 promotes the degradation of its client proteins. Its antiviral activity is directed against HSV, though the specific mechanism is less defined. |
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| ln Vitro |
Twenty ng/mL VEGF-induced tube, cell migration, and HUVEC templates are inhibited by AT-533 (0-1350 nM; 24 h or 48 h) [1]. Under hypoxic conditions, AT-533 (2 μM or 75 μM; 24 h) suppresses the coupling of HIF-1α/VEGF signaling in breast cancer cells and phosphorylates FAK, Akt/mTOR/p70S6K, and Erk1/2 [1]. AT-533 (0.5 μM; 2 h, 4 h) on chorion membrane (CAM) decreases the HSV-1-induced TNF-α, IL- Production of 1β and IL-6. AT-533 (10 nM, 50 nM; 48 h).
In vitro, AT-533 inhibits the activation of downstream signaling pathways, including Akt/mTOR/p70S6K, Erk1/2, and FAK. It also inhibits the migration, invasion, and tube formation of human umbilical vein endothelial cells (HUVECs), which are key processes in angiogenesis. These activities contribute to its antitumor and anti-angiogenic effects. |
| ln Vivo |
AT-533 (10 mg/kg; intraperitoneal injection; once daily for 21 days) Fluorescent dye MDA-MB-231 Expression of HIF-1α/VEGF coupling signaling-related proteins in breast cancer xenograft tumor transplant model [1]. AT-533 (1, 2, 4 mg/kg; i.p.; once daily for 30 days) did not produce death, recovery, weight loss, or adverse effects in the Sprague-Dawley subacute poisoning study [
In vivo, AT-533 has demonstrated the ability to suppress tumor growth and angiogenesis. By blocking the HIF-1α/VEGF/VEGFR-2 signaling pathway, it inhibits the formation of new blood vessels that are necessary for tumor growth. Its activity against HSV suggests potential for treating viral infections. However, specific in vivo efficacy data is detailed in the primary literature. |
| Enzyme Assay |
The inhibitory activity of AT-533 is assessed using various in vitro assays. Its effect on Hsp90 activity can be measured by assessing the degradation of Hsp90 client proteins. Its anti-angiogenic activity is evaluated using HUVEC tube formation assays. Its antiviral activity is assessed using HSV infection and replication assays. IC50 values for these activities would be determined.
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| Cell Assay |
Cell Viability Assay [1]
Cell Types: Human Umbilical Vein Endothelial Cells (HUVEC): MCF-7 and MDA-MB-231 Tested Concentrations: 0, 5.6, 16.7, 50, 150, 450 and 1350nM Incubation Duration[2]: 12 hrs (hours), 24 hrs (hours), 48 hrs (hours) and 72 hrs (hours). Experimental Results: Cell viability was inhibited at 48 hrs (hours) with an IC50 value of 50.1 nM. Western Blot Analysis[1] Cell Types: MCF-7 cells and MDA- MB-231 Cell Tested Concentrations: 5 nM, 10 nM, 50 nM and 75 nM Incubation Duration: 24 hrs (hours) Experimental Results: Inhibition of VEGF-2, phosphorylation of Akt, mTOR, Erk1/2, FAK. The cellular activity of AT-533 is evaluated in various cancer cell lines and in HUVECs. Cells are treated with AT-533, and its effect on cell viability, proliferation, migration, and signaling pathways is assessed. Its ability to inhibit angiogenesis is measured by its effect on HUVEC tube formation. The compound's effect on Hsp90 client protein levels is confirmed by Western blot. |
| Animal Protocol |
Animal/Disease Models: MDA-MB-231 breast cancer xenograft male C57BL/6 mice [1]
Doses: 10 mg/kg; 3]. Route of Administration: intraperitoneal (ip) injection; one time/day for 21 days. Experimental Results: The expression of HIF-1α and VEGF was Dramatically down-regulated. In animal studies, AT-533 would typically be administered to tumor-bearing mice to assess its antitumor efficacy. The route of administration (e.g., intraperitoneal, oral) and dosing regimen would be determined based on its pharmacokinetic properties. Tumor growth inhibition and markers of angiogenesis would be measured. Its antiviral efficacy could be evaluated in models of HSV infection. |
| ADME/Pharmacokinetics |
AT-533 is a small molecule with a molecular weight of 394.47 and a formula of C23H30N4O3. It is soluble in DMSO (25 mg/mL) and is typically stored as a powder at -20°C. Detailed pharmacokinetic parameters, such as half-life and bioavailability, are not extensively documented in publicly available sources.
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| Toxicity/Toxicokinetics |
Toxicology data for AT-533 is limited, as it is a research compound. Its safety profile has not been established in formal toxicology studies. As an Hsp90 inhibitor, its potential for off-target effects and toxicity would need to be carefully evaluated. Its use is limited to research applications.
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| References |
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| Additional Infomation |
AT-533 (CAS: 908112-37-8) is a dual-action research tool that inhibits both Hsp90 and HSV. Its ability to block multiple signaling pathways involved in tumor growth and angiogenesis makes it a valuable compound for cancer research. Its antiviral activity adds to its utility as a research probe. It is used to study the role of Hsp90 in cancer and the potential of Hsp90 inhibition as a therapeutic strategy.
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| Molecular Formula |
C23H30N4O3
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|---|---|
| Molecular Weight |
410.509305477142
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| Exact Mass |
410.231
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| CAS # |
908112-37-8
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| Related CAS # |
908112-37-8
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| PubChem CID |
24820800
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| Appearance |
Off-white to light yellow solid
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| LogP |
3.3
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
30
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| Complexity |
661
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=NN(C2=C1C(=O)CC(C2)(C)C)C3=CC(=C(C=C3)C(=O)N)NC4CCC(CC4)O
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| InChi Key |
FMOSGTTYAFQMSD-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H30N4O3/c1-13-21-19(11-23(2,3)12-20(21)29)27(26-13)15-6-9-17(22(24)30)18(10-15)25-14-4-7-16(28)8-5-14/h6,9-10,14,16,25,28H,4-5,7-8,11-12H2,1-3H3,(H2,24,30)
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| Chemical Name |
2-[(4-hydroxycyclohexyl)amino]-4-(3,6,6-trimethyl-4-oxo-5,7-dihydroindazol-1-yl)benzamide
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| Synonyms |
AT-533; AT533; AT 533
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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 |
| 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: ~33.3 mg/mL (81.2 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.09 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 (6.09 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 (6.09 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 | 2.4360 mL | 12.1800 mL | 24.3599 mL | |
| 5 mM | 0.4872 mL | 2.4360 mL | 4.8720 mL | |
| 10 mM | 0.2436 mL | 1.2180 mL | 2.4360 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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