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5mg |
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25mg |
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Purity: =98.18%
MT-802 is a novel and potent PROTAC-mediated degrader which binds fewer off-target kinases than ibrutinib does, thereby inducing BTK knockdown, and recruiting BTK to the cereblon E3 ubiquitin ligase complex to trigger BTK ubiquitination and degradation via the proteasome. For patients suffering from chronic lymphocytic leukemia (CLL) and other B-cell malignancies, inhibition of Bruton's tyrosine kinase (BTK) with the irreversible inhibitor ibrutinib has emerged as a transformative treatment option. However, more than 80% of CLL patients develop resistance because of a cysteine to serine mutation at the site covalently bound by ibrutinib (C481S). For C481S patients who show relapse to ibrutinib, there is currently no effective treatment option, and these patients do not respond well. In order to overcome this, MT-802 was created as a PROteolysis TArgeting Chimera (PROTAC) that causes BTK that is both wild-type and C481S mutant to degrade. In order to cause BTK ubiquitination and proteasome degradation, MT-802 enlists BTK to the cereblon E3 ubiquitin ligase complex. In comparison to ibrutinib, MT-802 binds fewer off-target kinases while maintaining a potency against wild-type and C481S BTK that is equivalent to >99% degradation at nanomolar concentrations. Whereas ibrutinib cannot lower the pool of active, phosphorylated BTK, MT-802 can in cells isolated from CLL patients with the C481S mutation. All together, these findings offer a foundation for additional preclinical research on BTK PROTACs as a novel therapeutic approach for C481S mutant CLL.
Targets |
BTK (DC50 = 1 nM)
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ln Vitro |
MT-802 degrades BTK with a DC50 of 9.1 nM, reaching a maximum degradation threshold of 250 nM[1].
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References |
Molecular Formula |
C41H41N9O8
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Molecular Weight |
787.8197
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Exact Mass |
787.3078093
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CAS # |
2231744-29-7
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Related CAS # |
2231744-29-7
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Appearance |
Solid
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SMILES |
C1CC(=O)NC(=O)C1N2C(=O)C3=C(C2=O)C=C(C=C3)NC(=O)COCCOCCN4CCC(CC4)N5C6=NC=NC(=C6C(=N5)C7=CC=C(C=C7)OC8=CC=CC=C8)N
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InChi Key |
AJTLGUJXIKEZCQ-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C41H41N9O8/c42-37-35-36(25-6-9-29(10-7-25)58-28-4-2-1-3-5-28)47-50(38(35)44-24-43-37)27-14-16-48(17-15-27)18-19-56-20-21-57-23-34(52)45-26-8-11-30-31(22-26)41(55)49(40(30)54)32-12-13-33(51)46-39(32)53/h1-11,22,24,27,32H,12-21,23H2,(H,45,52)(H2,42,43,44)(H,46,51,53)
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Chemical Name |
2-[2-[2-[4-[4-amino-3-(4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]ethoxy]ethoxy]-N-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]acetamide
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Synonyms |
MT802; MT 802; MT-802
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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: ~100 mg/mL (~126.9 mM)
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.17 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 (3.17 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 (3.17 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 | 1.2693 mL | 6.3466 mL | 12.6933 mL | |
5 mM | 0.2539 mL | 1.2693 mL | 2.5387 mL | |
10 mM | 0.1269 mL | 0.6347 mL | 1.2693 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.