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| 5mg |
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| 25mg |
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| 50mg |
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| 100mg |
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Purity: =99.23%
Irbinitinib (formerly known as ARRY-380; ONT-380; Tucatinib; Tukysa) is a potent and selective small molecule HER2 inhibitor that has been given the go-ahead to treat breast cancer. Its IC50 value is 8 nM, its potency against truncated p95-HER2 is equal, and its selectivity for HER2 is 500 times higher than that of EGFR. Irbinitinib works by preventing HER2 and its downstream effector, Akt, from proliferating and becoming phosphorylated. On the other hand, it only marginally suppresses phosphorylation and proliferation in EGFR overexpressing cell lines, suggesting that Irbinitinib may be able to inhibit HER2 signaling without having the deleterious effects of EGFR inhibition. It could therefore be applied as an anticancer agent.
| Targets |
RETWT (IC50 = 1.29 nM); RETV804M (IC50 = 1.97 nM ); RETV804M (IC50 = 0.99 nM)
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| ln Vitro |
ONT-380 has nanomolar activity against purified HER2 enzyme and is approximately 500-fold selective for HER2 versus EGFR in cell-based assays. ONT-380 (ARRY-380) selectively inhibits the receptor tyrosine kinase HER2 relative to EGFR. In HER2 overexpressing cell lines, ONT-380 blocks proliferation and the phosphorylation of HER2 and its downstream effector, Akt. By contrast, in the EGFR overexpressing cell lines, it weakly inhibits phosphorylation and proliferation, demonstrating that ONT-380 may have potential to block HER2 signaling without causing the toxicities of EGFR inhibition.
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| ln Vivo |
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| Enzyme Assay |
Irbinitinib, formerly known as ARRY-380 and ONT-380 or Tucatinib, is a potent and selective small molecule inhibitor of HER2 with IC50 value of 8 nM, it is equally potent against truncated p95-HER2, and is 500-fold more selective for HER2 versus EGFR. Irbinitinib acts by blocking the proliferation and phosphorylation of HER2 and its downstream effector, Akt. By contrast, in the EGFR overexpressing cell lines, it weakly inhibits phosphorylation and proliferation, demonstrating that Irbinitinib may have potential to block HER2 signaling without causing the toxicities of EGFR inhibition. Therefore, it has the potential to be used as an anticancer agent.
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| Cell Assay |
ONT-380 has nanomolar activity against purified HER2 enzyme and is approximately 500-fold selective for HER2 versus EGFR in cell-based assays. In the EGFR overexpressing cell lines, it weakly inhibits phosphorylation and proliferation, demonstrating that Irbinitinib may have potential to block HER2 signaling without causing the toxicities of EGFR inhibition.
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| References |
Clin Cancer Res.2017 Jul 15;23(14):3529-3536.
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| Molecular Formula |
C26H24N8O2
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|---|---|
| Molecular Weight |
480.2022
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| Exact Mass |
480.2022
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| Elemental Analysis |
C, 64.99; H, 5.03; N, 23.32; O, 6.66
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| CAS # |
937263-43-9
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| Related CAS # |
Tucatinib hemiethanolate;1429755-56-5
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| Appearance |
Solid powder
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| SMILES |
CC1=C(C=CC(=C1)NC2=NC=NC3=C2C=C(C=C3)NC4=NC(CO4)(C)C)OC5=CC6=NC=NN6C=C5
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| InChi Key |
SDEAXTCZPQIFQM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H24N8O2/c1-16-10-17(5-7-22(16)36-19-8-9-34-23(12-19)28-15-30-34)31-24-20-11-18(4-6-21(20)27-14-29-24)32-25-33-26(2,3)13-35-25/h4-12,14-15H,13H2,1-3H3,(H,32,33)(H,27,29,31)
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| Chemical Name |
6-N-(4,4-dimethyl-5H-1,3-oxazol-2-yl)-4-N-[3-methyl-4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)phenyl]quinazoline-4,6-diamine
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| Synonyms |
ONT 380; ARRY380; ONT380; ARRY 380; ONT-380; Irbinitinib; ARRY-380; Tukysa; Tucatinib
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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: ~96 mg/mL ( ~199.8 mM）
Water: <15 mg/mL Ethanol: Insoluble |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.62 mg/mL (5.45 mM) (saturation unknown) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.62 mg/mL (5.45 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. 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: 2.08 mg/mL (4.33 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Solubility in Formulation 4: 2.08 mg/mL (4.33 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 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. Solubility in Formulation 5: ≥ 2.08 mg/mL (4.33 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 6: 5%DMSO+40%PEG300+5%Tween 80+50%ddH2O：0.8mg/ml Solubility in Formulation 7: 10 mg/mL (20.81 mM) in 30 % SBE-β-CD (add these co-solvents sequentially from left to right, and one by one), Suspension solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0825 mL | 10.4123 mL | 20.8247 mL | |
| 5 mM | 0.4165 mL | 2.0825 mL | 4.1649 mL | |
| 10 mM | 0.2082 mL | 1.0412 mL | 2.0825 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 |
| NCT03054363 | not recruiting | Drug: Tucatinib in Combination with Palbociclib and Letrozole (Safety Cohort) | Breast Cancer | University of Colorado, Denver | November 27, 2017 | Phase 1 |
| NCT05382364 | not recruiting | Drug: Tucatinib | Metastatic HER2+ Advanced Breast Cancer | Merck Sharp & Dohme LLC | June 29, 2022 | Phase 1 |
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