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Purity: ≥98%
ASP3026 (ASP-3026; ASP 3026) is an orally bioavailable inhibitor of ALK (anaplastic lymphoma kinase) with potential antineoplastic activity. It inhibits ALK with an IC50 of 3.5 nM. Treatment for ALK-positive non-small cell lung cancer (NSCLC) has been proven to be effective when targeting ALK. High anti-proliferative activity of ASP3026 is shown in vitro against a variety of cancer cells, including NCI-H2228 and 3T3 cells that express variants 1, 2, and 3 of EML4-ALK. Additionally, it demonstrated strong in vivo antitumor efficacy in mice that were xenografted with NCI-H2228 cells that expressed EML4-ALK.
| Targets |
ALK (IC50 = 3.5 nM)
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| ln Vitro |
ASP3026 exhibits a more focused inhibition of ALK than PF02341066 in a Tyr-kinase panel. NCI-H2228 is a human NSCLC tumor cell line that endogenously expresses EML4-ALK variant 3. At an IC50 value of 64.8 nM, ASP3026 inhibits the growth of this cell line.
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| ln Vivo |
ASP3026 causes dose-dependent anti-tumor effects beginning at 1 mg/kg with strong regression at 10, 30, and 100 mg/kg when given orally twice daily for 14 days to mice bearing subcutaneous NCI-H2228 tumor xenografts.
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| Enzyme Assay |
ASP3026 exhibited an inhibitory spectrum distinct from crizotinib, a dual ALK/MET inhibitor, and inhibited ALK activity in an ATP-competitive manner.
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| Cell Assay |
ASP3026, when administered orally, was well absorbed in tumor tissues in mice xenografted with NCI-H2228 cells expressing EML4-ALK. Its concentrations in tumor tissues exceeded those in plasma by more than ten times, and it caused tumor regression with a therapeutic margin spanning from highly effective to highly toxic doses. Paclitaxel and pemetrexed's antitumor activities were improved in the same mouse model by ASP3026, without compromising body weight. Strong antitumor effects were also demonstrated by ASP3026 in hEML4-ALK transgenic mice, where it led to tumor shrinkage to undetectable levels and increased survival in mice receiving intrapleural NCI-H2228 xenografts. Relative to mice treated with crizotinib, tumors in the intrahepatic xenograft model utilizing NCI-H2228 cells continuously regressed when ASP3026 was administered. Finally, ASP3026 shown significant antitumor activity against EML4-ALK-expressing cells carrying the L1196M gatekeeper position mutation, which results in crizotinib resistance. All things considered, these results suggest that ASP3026 may be effective in treating NSCLC and should help patients whose cancer has an abnormal ALK expression receive better treatment outcomes.
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| References |
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| Molecular Formula |
C29H40N8O3S
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| Molecular Weight |
580.74
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| Exact Mass |
580.29
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| Elemental Analysis |
C, 59.98; H, 6.94; N, 19.29; O, 8.26; S, 5.52
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| CAS # |
1097917-15-1
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| Related CAS # |
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| Appearance |
Solid powder
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| SMILES |
CC(C)S(=O)(=O)C1=CC=CC=C1NC2=NC(=NC=N2)NC3=C(C=C(C=C3)N4CCC(CC4)N5CCN(CC5)C)OC
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| InChi Key |
MGGBYMDAPCCKCT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C29H40N8O3S/c1-21(2)41(38,39)27-8-6-5-7-25(27)33-29-31-20-30-28(34-29)32-24-10-9-23(19-26(24)40-4)36-13-11-22(12-14-36)37-17-15-35(3)16-18-37/h5-10,19-22H,11-18H2,1-4H3,(H2,30,31,32,33,34)
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| Chemical Name |
2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)-1,3,5-triazine-2,4-diamine
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| Synonyms |
ASP-3026; ASP 3026; ASP3026
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2 mg/mL (3.44 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 20.0 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 mg/mL (3.44 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 20.0 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 mg/mL (3.44 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 | 1.7219 mL | 8.6097 mL | 17.2194 mL | |
| 5 mM | 0.3444 mL | 1.7219 mL | 3.4439 mL | |
| 10 mM | 0.1722 mL | 0.8610 mL | 1.7219 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT01401504 | Completed | Drug: ASP3026 | Solid Tumor | Astellas Pharma Inc | May 2011 | Phase 1 |
| NCT01284192 | Completed | Drug: ASP3026 | Solid Tumor B-Cell Lymphoma |
Astellas Pharma Inc | December 2010 | Phase 1 |
ASP3026 reduces the tyrosine kinase activity of NPM-ALK, downregulates the phosphorylation of NPM-ALK and target proteins, and induces biochemical effects consistent with apoptosis. Oncotarget. 2014 Jul; 5(14): 5750–5763. |
ASP3026 overcomes the resistance to crizotinib in NPM-ALK+ ALCL. |
ASP3026 suppresses NPM-ALK+ ALCL tumor cell growth in vivo. Oncotarget. 2014 Jul 30;5(14):5750-63. |
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