| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg | |||
| 100mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
HER4 (IC50 = 8.5 nM); HER2 (IC50 = 13 nM); EGFR (IC50 = 65 nM); BMX (IC50 = 4.9 nM); BLK (IC50 = 31 nM); JAK3 (IC50 = 33 nM); SLK (IC50 = 25 nM); LOK (IC50 = 86 nM)
TAS0728 targets HER2 (ERBB2) kinase, covalently binding to C805 and irreversibly inhibiting its activity. It also inhibits BMX (IC50=4.9 nM), HER4 (IC50=8.5 nM), BLK (IC50=31 nM), EGFR (IC50=65 nM), JAK3 (IC50=33 nM), SLK (IC50=25 nM), and LOK (IC50=86 nM). It blocks downstream PI3K/AKT and MAPK signaling pathways. |
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| ln Vitro |
TAS0728 selectively inhibits the kinase activity of HER2 by covalently binding to it at C805. High ATP concentrations have no effect on TAS0728's inhibitory activity once it binds to HER2 kinase. TAS0728 exhibits superior HER2 specificity compared to wild-type EGFR. Both wild-type and mutant HER2 have their phosphorylation significantly inhibited by TAS0728. The phosphorylation of HER2, HER3, and downstream effectors is robustly and persistently inhibited by TAS0728, which causes HER2-amplified breast cancer cells to undergo apoptosis. [1]
In vitro, TAS0728 is a potent HER2 inhibitor with an IC50 of 13 nM. It exhibits robust and sustained inhibition of the phosphorylation of HER2, HER3, and downstream effectors, thereby inducing apoptosis of HER2-amplified breast cancer cells. It shows a broad kinase inhibition profile against multiple targets including BMX, HER4, BLK, EGFR, JAK3, SLK, and LOK. |
| ln Vivo |
TAS0728 causes apoptosis in tumor tissues of a xenograft model by demonstrating strong and long-lasting inhibition of the phosphorylation of HER2, HER3, and downstream effectors. In mouse models of xenografts with tumors driven by the HER2 signal, TAS0728 causes tumor regression; in a mouse model of peritoneal dissemination with cancer cells driven by the HER2 signal, it shows a benefit to survival without obvious toxicity.[1]
In vivo, TAS0728 has demonstrated potent antitumor activity in preclinical models, including xenograft models. It induces apoptosis in tumor tissues of xenograft models bearing HER2-driven cancer cells. The compound is orally active and has shown efficacy in peritoneal dissemination mouse models. |
| Enzyme Assay |
Kinase profiling is a technique used by Carna Biosciences to quantify the inhibitory activity of HER2 kinase. Based on HER2's in vitro peptide substrate phosphorylation activity, the 50% inhibitory concentration (IC50 value) of TAS0728 is calculated. Three separate studies are carried out. Reaction Biology Corporation utilizes the Kinase Panel Assay to test TAS0728's inhibitory activity against 386 or 374 kinases. The assays are carried out in duplicate mode with TAS0728 concentrations of 0.1, 1, and 10 μmol/L. 10 μmol/L ATP is present when reactions are occurring.
TAS0728 is a covalent-binding HER2 inhibitor. In vitro kinase assays measure its inhibition of HER2 kinase activity, with an IC50 of 13 nM. Binding to HER2 at C805 is confirmed through covalent binding studies. Selectivity is assessed by profiling against a panel of kinases including BMX, HER4, BLK, EGFR, JAK3, SLK, and LOK. |
| Cell Assay |
In 6-well plates, cells are sown, and they are cultured for an entire night. For three hours, compounds are added to the culture medium at the indicated concentrations. After that, the medium is harvested for Western blot analysis. The MCF10A cell line is used for studies in which 12-well plates are seeded with cells and left overnight to culture. After adding TAS0728 to the culture medium, it is incubated for three hours. To carry out a Western blot analysis, the cells are extracted. 100-mm dishes are used to seed and culture SK-BR-3 cells for the duration of the pharmacodynamics time-course study. Add TAS0728, then let it sit for three or forty-eight hours. To carry out a Western blot analysis, the cells are extracted.
In vitro cell-based assays for TAS0728 use HER2-amplified breast cancer cells. Cells are treated with serial dilutions of the compound, and phosphorylation of HER2, HER3, and downstream effectors is measured by Western blotting. Apoptosis is assessed by measuring cleaved caspase-3 and PARP. Cell viability and proliferation are measured using standard assays. |
| Animal Protocol |
6-week-old male nude mice (BALB/cAJcl-nu/nu)
7.5 mg/kg, 15 mg/kg, 30 mg/kg, 60 mg/kg Oral gavage In vivo efficacy is evaluated using xenograft models bearing HER2-driven cancer cells. The compound is administered orally, and tumor growth inhibition is measured. Apoptosis in tumor tissues is assessed by immunohistochemistry. Peritoneal dissemination mouse models are used to evaluate efficacy against metastatic disease. |
| ADME/Pharmacokinetics |
TAS0728 has a molecular formula of C₂₆H₂₈F₃N₇O₃ and a molecular weight of 543.54 g/mol. It is orally bioavailable. The compound is soluble in DMSO and is stored at -20°C. Pharmacokinetic parameters including half-life and bioavailability are documented in research publications.
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| Toxicity/Toxicokinetics |
Toxicity data for TAS0728 are available from preclinical safety studies. As a covalent HER2 inhibitor, the compound's safety profile is assessed in standard toxicology studies. The compound is for research use only and is not approved for clinical use. Appropriate safety precautions should be taken during handling.
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| References | |
| Additional Infomation |
TAS0728 is a potent, selective, orally active, irreversible, and covalent-binding HER2 inhibitor with an IC50 of 13 nM. It binds to HER2 at C805 and blocks downstream PI3K/AKT and MAPK signaling. TAS0728 has shown potent antitumor activity in preclinical models. It is also known as TAS-0728 and is intended for laboratory research use only.
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| Molecular Formula |
C26H32N8O3
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|---|---|
| Molecular Weight |
504.584084510803
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| Exact Mass |
504.26
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| Elemental Analysis |
C, 61.89; H, 6.39; N, 22.21; O, 9.51
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| CAS # |
2088323-16-2
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| Related CAS # |
2088323-16-2
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| PubChem CID |
130275856
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| Appearance |
White to off-white solid powder
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| LogP |
1.7
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
37
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| Complexity |
869
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC1=C(C=CC(=C1C)NC(=O)C2=NN(C3=NC=NC(=C23)N)[C@@H]4CCCN(C4)C(=O)C=C)CC(=O)N(C)C
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| InChi Key |
JCCIICHPRAAMGK-GOSISDBHSA-N
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| InChi Code |
InChI=1S/C26H32N8O3/c1-6-20(35)33-11-7-8-18(13-33)34-25-22(24(27)28-14-29-25)23(31-34)26(37)30-19-10-9-17(15(2)16(19)3)12-21(36)32(4)5/h6,9-10,14,18H,1,7-8,11-13H2,2-5H3,(H,30,37)(H2,27,28,29)/t18-/m1/s1
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| Chemical Name |
4-amino-N-[4-[2-(dimethylamino)-2-oxoethyl]-2,3-dimethylphenyl]-1-[(3R)-1-prop-2-enoylpiperidin-3-yl]pyrazolo[3,4-d]pyrimidine-3-carboxamide
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| Synonyms |
TAS 0728; TAS0728; TAS-0728
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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: 100~125 mg/mL (198.2~247.7 mM）
Ethanol: ~5 mg/mL (~9.9 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.12 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 20.8 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: ≥ 2.08 mg/mL (4.12 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 20.8 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.12 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 | 1.9818 mL | 9.9092 mL | 19.8185 mL | |
| 5 mM | 0.3964 mL | 1.9818 mL | 3.9637 mL | |
| 10 mM | 0.1982 mL | 0.9909 mL | 1.9818 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.
Link: https://clinicaltrials.gov/ct2/show/NCT03410927
Conditions:Advanced Solid Tumors With HER2 Abnormalities|Advanced Solid Tumors With HER3 Abnormalities
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