| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg |
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| 1g |
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| Other Sizes |
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Purity: ≥98%
Brigatinib analog is derived from Brigatinib (AP-26113; Alunbrig), an oral bioavailable ALK (anaplastic lymphoma kinase) inhibitor that the FDA approved in 2017 for the treatment of non-small cell lung cancer (NSCLC) that has met ALK-positive metastatic criteria.
| Targets |
ALK (IC50 = 0.07 nM); EGFR (IC50 = 28.4 nM); IGF1R (IC50 = 32 nM); EGFR (IC50 = 36.8 nM); EGFR (IC50 = 36.8 nM)
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| ln Vitro |
AP26113-analog and brgatinib, both of which have IC50 values of less than 100 nM, are potent against triple-mutant EGFR. When EGFR mutations of any kind are expressed in cells, AP26113-analog inhibits the phosphorylation of EGFR and its downstream signal path[2].
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| ln Vivo |
AP26113 (< 50 mg/kg) inhibits p-ALK in the tumor of Karpas-299 xenograft mice model in a dose-dependent manner. AP26113 (< 50 mg/kg) inhibits tumor growth in the Karpas-299 and H3122 xenograft mouse models in a dose-dependent manner. Positive characteristics of AP26113 include a low level of inhibition of the main CYP isoforms and a moderate in vitro plasma protein binding (47%, 70%, and 76% in human, rat, and mouse). Rats show good tolerance to AP26113 (10 mg/kg), with a Cmax of 2587 ng/mL and an AUC of 41120 hr.ng/mL. In the model of HCC827(EGFR-DEL) or HCC827(EGFR-DEL/T790M) xenograft mice, AP26113 (25 mg/kg) causes tumor regression.
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| Enzyme Assay |
A HotSpotSM kinase profile of 289 kinases is carried out in vitro. The experiment is carried out with brigatinib concentrations ranging from 0.05 nM to 1 μM in the presence of 10 μM [33P]-ATP.
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| Cell Assay |
For three-day cell viability assays, black transparent-bottom 96-well plates are plated with 2,000, 1,500, or 2,000 cells per well of Ba/F3, PC9, or MGH121, respectively. Each TKI is applied to the cells in a 10-dose range of 0.3 nM to 10 μM on the same day for Ba/F3 cells and the following day for PC9 and MGH121 cells. The CellTiter-Glo assay is used to measure cell viability 72 hours after the start of drug treatment.
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| Animal Protocol |
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| References |
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| Molecular Formula |
C26H34CLN6O2P
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|---|---|
| Molecular Weight |
529.01
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| Exact Mass |
528.22
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| Elemental Analysis |
C, 59.03; H, 6.48; Cl, 6.70; N, 15.89; O, 6.05; P, 5.85
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| CAS # |
1197958-12-5
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| Related CAS # |
1197958-12-5 (analog);1197953-54-0;
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| Appearance |
white solid powder
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| SMILES |
CN(C)C1CCN(CC1)C2=CC(=C(C=C2)NC3=NC=C(C(=N3)NC4=CC=CC=C4P(=O)(C)C)Cl)OC
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| InChi Key |
OVDSPTSBIQCAIN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H34ClN6O2P/c1-32(2)18-12-14-33(15-13-18)19-10-11-21(23(16-19)35-3)30-26-28-17-20(27)25(31-26)29-22-8-6-7-9-24(22)36(4,5)34/h6-11,16-18H,12-15H2,1-5H3,(H2,28,29,30,31)
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| Chemical Name |
5-chloro-2-N-[4-[4-(dimethylamino)piperidin-1-yl]-2-methoxyphenyl]-4-N-(2-dimethylphosphorylphenyl)pyrimidine-2,4-diamine
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| Synonyms |
AP-26113; Brigatinib-analog; AP26113; AP 26113; AP 26113-analog; AP26113-analog; AP-26113-analog
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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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.73 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 (4.73 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 (4.73 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: NMP+polyethylene glycol 300 (10+90, v+v): 1 mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8903 mL | 9.4516 mL | 18.9032 mL | |
| 5 mM | 0.3781 mL | 1.8903 mL | 3.7806 mL | |
| 10 mM | 0.1890 mL | 0.9452 mL | 1.8903 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 |
| NCT03410108 | Completed | Drug: Brigatinib | ALK-positive Advanced NSCLC | Takeda | January 29, 2018 | Phase 2 |
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