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Avapritinib:WO 2021/183709 A1.
Purity: =99.25%
Avapritinib (formerly known as BLU-285; trade name Ayvakit) is an oral, potent and selective small molecule inhibitor of PDGFRα D842V and KIT Exon 17 mutants (IC50=0.5 nM) with anticancer activity. In 2020, it received approval to treat gastrointestinal stromal tumors (GIST) that have spread. In order to treat systemic mastocytosis (SM), a disorder of the mast cells where a KIT Exon 17 mutation is the main cause of disease, avapritinib was being developed as a highly targeted therapy. Patients with advanced systemic mastocytosis saw quick and long-lasting disease control in a phase I trial. Of the patients, 56% had a complete or partial response, for an overall response rate of 72%. Adverse events were mostly mild to moderate in nature, and none of the patients stopped their treatment because of them. Furthermore, BLU-285 might be a useful treatment choice for AMLs with t(8;21) mutations and KIT exon 17 mutations in CBF-AMLs.
| Targets |
KIT D816V (IC50 = 0.27 nM); PDGFRA D842V (IC50 = 0.24 nM)
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| ln Vitro |
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| ln Vivo |
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| Enzyme Assay |
Biochemical in vitro activity of avapritinib (BLU-285) on the KIT exon 17 mutant enzyme, KIT D816V (IC50=0.27 nM), has been demonstrated.
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| Cell Assay |
Autophosphorylation in the human mast cell leukemia cell line HMC1.2 and the mouse mastocytoma cell line P815, with IC50 values of 4 and 22 nM, respectively, is used to assess the cellular activity of avapritinib on KIT D816 mutants. Avapritinib potently inhibits cellular proliferation (IC50=75 nM), downstream signaling, and KIT N822K mutant autophosphorylation (IC50=40 nM) in Kasumi-1 cells, a t(8;21)-positive AML cell line with a KIT exon 17 N822K mutation.
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| Animal Protocol |
Mice: The effectiveness of avapritinib (BLU-285) in KIT exon 17-mutated CBF-AML is evaluated in a femoral injection model of Kasumi-1 luc+ AML NOG SCID mice. Mice are dosed with avapritinib orally once daily at 10 mg/kg or 30 mg/kg through day 45 after a 21-day post-injection latency period.
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| References |
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| Molecular Formula |
C26H27FN10
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| Molecular Weight |
498.56
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| Exact Mass |
498.24
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| Elemental Analysis |
C, 62.64; H, 5.46; F, 3.81; N, 28.09
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| CAS # |
1703793-34-3
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| Related CAS # |
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| Appearance |
White to off-white solid powder
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| SMILES |
C[C@](C1=CC=C(C=C1)F)(C2=CN=C(N=C2)N3CCN(CC3)C4=NC=NN5C4=CC(=C5)C6=CN(N=C6)C)N
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| InChi Key |
DWYRIWUZIJHQKQ-SANMLTNESA-N
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| InChi Code |
InChI=1S/C26H27FN10/c1-26(28,20-3-5-22(27)6-4-20)21-13-29-25(30-14-21)36-9-7-35(8-10-36)24-23-11-18(16-37(23)33-17-31-24)19-12-32-34(2)15-19/h3-6,11-17H,7-10,28H2,1-2H3/t26-/m0/s1
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| Chemical Name |
(1S)-1-(4-fluorophenyl)-1-[2-[4-[6-(1-methylpyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl]piperazin-1-yl]pyrimidin-5-yl]ethanamine
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| Synonyms |
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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: ≥ 2.5 mg/mL (5.01 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 (5.01 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 (5.01 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: 2% DMSO+40% PEG 300+2% Tween 80+ddH2O: 4mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0058 mL | 10.0289 mL | 20.0578 mL | |
| 5 mM | 0.4012 mL | 2.0058 mL | 4.0116 mL | |
| 10 mM | 0.2006 mL | 1.0029 mL | 2.0058 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 |
| NCT03580655 | Active Recruiting |
Drug: Avapritinib | Advanced Systemic Mastocytosis Mast Cell Leukemia |
Blueprint Medicines Corporation | November 21, 2018 | Phase 2 |
| NCT04825574 | Active Recruiting |
Drug: Avapritinib | Gastrointestinal Stromal Tumors | Blueprint Medicines Corporation | May 21, 2021 | Phase 4 |
| NCT03731260 | Active Recruiting |
Drug: Avapritinib Drug: Placebo |
Indolent Systemic Mastocytosis | Blueprint Medicines Corporation | April 16, 2019 | Phase 2 |
| NCT04773782 | Recruiting | Drug: avapritinib | CNS Tumor Relapsed Solid Neoplasm |
Blueprint Medicines Corporation | February 24, 2022 | Phase 1 Phase 2 |
| NCT04771520 | Recruiting | Drug: Avapritinib | Metastatic Sarcoma Metastatic Melanoma |
M.D. Anderson Cancer Center | January 20, 2021 | Phase 2 |
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