DZD1516
Based on 1 Customer Validation
DZD1516 is an orally active, reversible, blood-brain barrier (BBB)-penetrant selective HER2 tyrosine kinase inhibitor with an IC50 of 0.56 nM against HER2. DZD1516 is not a substrate of P-gp or BCRP, and exhibits high passive permeability. DZD1516 inhibits tumor growth in HER2-positive brain metastasis, leptomeningeal metastasis and subcutaneous xenograft models, and can be used for research related to HER2-positive breast cancer and central nervous system metastasis.
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- Pureza: 99.62%
- No. CAS: 2387570-00-3
- Fòrmula: C28H27F2N7O3
- Peso molecular:547.56
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Almacenamiento:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Actividad biológica
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Chemical Information
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Solvente y solubilidad
- Pureza y Documentación
- Referencias
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Help & FAQs
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Actividad biológica
Descripciòn
IC50 & Target
[3]|
HER2 0.56 nM (IC50) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| BT-474 | IC50 |
4.4 nM
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Inhibition of phospho-HER2 (pHER2) in HER2-overexpressing BT474C1 cells via cell-based assay.
Inhibition of phospho-HER2 (pHER2) in HER2-overexpressing BT474C1 cells via cell-based assay.
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37415239 |
| A-431 | IC50 |
1455 nM
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Inhibition of phospho-EGFR (pEGFR) in wild-type EGFR-overexpressing A431 cells via cell-based assay.
Inhibition of phospho-EGFR (pEGFR) in wild-type EGFR-overexpressing A431 cells via cell-based assay.
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37415239 |
| BT-474 | GI50 |
20 nM
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Antiproliferative activity against HER2-overexpressing BT474C1 cells via cell proliferation assay.
Antiproliferative activity against HER2-overexpressing BT474C1 cells via cell proliferation assay.
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37415239 |
| A-431 | GI50 |
8867 nM
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Antiproliferative activity against wild-type EGFR-overexpressing A431 cells via cell proliferation assay.
Antiproliferative activity against wild-type EGFR-overexpressing A431 cells via cell proliferation assay.
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37415239 |
In Vitro
DZD1516 potently inhibits purified recombinant human HER2 kinase with an IC50 of 0.56 nM[3].
DZD1516 demonstrates high selectivity for HER2 kinase over a panel of 121 other recombinant human kinases[3].
DZD1516 exhibits high passive permeability in Caco-2 cells and is not a substrate of P-gp or BCRP transporters, supporting its potential for blood-brain barrier penetration[3].
DZD1516 inhibits hERG potassium channels with an IC50 of 3.29 μM in an in vitro safety pharmacology assay[3].
DZD1516 potently inhibits pHER2 in BT474C1 cells with an IC50 of 4.4 nM and exhibits over 300-fold selectivity over wild-type EGFR expressed in A431 cells[3].
DZD1516 potently inhibits the proliferation of HER2-overexpressing BT474C1 cells with a GI50 of 20 nM and has minimal activity against wild-type EGFR-overexpressing A431 cells[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
DZD1516 (100-150 mg/kg; p.o.; twice daily; for 2 weeks) exhibits potent dose-dependent antitumor activity in a mouse model of leptomeningeal metastasis of breast cancer, with a maximum TGI of up to 81% at the dose of 150 mg/kg twice daily[3].
DZD1516 (100-150 mg/kg; p.o.; twice daily; for 14 consecutive days) induces tumor regression in a subcutaneous breast cancer xenograft model in mice when administered at doses of 100 mg/kg and 150 mg/kg twice daily, with efficacy comparable to that of the control drug[3].
DZD1516 (100 mg/kg; p.o.; twice daily) enhances the anti-tumor activity of T-DM1 in a mouse model of breast cancer brain metastasis[3].
DZD1516 (6.25 mg/kg; p.o.; twice daily) enhances the anti-tumor activity of T-DM1 in a subcutaneous breast cancer xenograft mouse model[3].
Combination treatment with DZD1516 (6.25 mg/kg; p.o.; twice daily; for 28 consecutive days) and T-DXd (HY-138298A) induces complete tumor regression in a subcutaneous breast cancer xenograft mouse model[3].
DZD1516 (25-150 mg/kg; p.o.; single administration) exhibits a dose-dependent inhibitory effect on pHER2 in a mouse subcutaneous breast cancer xenograft model, and the inhibitory effect can last up to 24 h at a single dose of 150 mg/kg[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Nude mice[3]
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Dosage:100 mg/kg; 150 mg/kg
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Administration:p.o.; twice daily; 3 weeks
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Result:Produced 48% tumor growth inhibition (TGI) at 100 mg/kg and 79% TGI at 150 mg/kg.
Demonstrated antitumor activity at 150 mg/kg superior to a comparator at its mouse MTD of 75 mg/kg.
Showed profound reduction in intracranial tumor signals at both doses after 3 weeks of treatment.
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Animal Model:Nude mice[3]
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Dosage:100 mg/kg; 150 mg/kg
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Administration:p.o.; twice daily; 2 weeks
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Result:Generated 57% tumor growth inhibition (TGI) at 100 mg/kg and 81% TGI at 150 mg/kg.
Showed marked reduction in leptomeningeal tumor signals at both doses after 2 weeks of treatment, with efficacy numerically better than a comparator.
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Animal Model:Nude mice[3]
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Dosage:100 mg/kg; 150 mg/kg
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Administration:p.o.; twice daily; 14 days
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Result:Induced dose-dependent tumor remission at both 100 mg/kg and 150 mg/kg, with efficacy equivalent to a comparator.
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Animal Model:Nude mice[3]
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Dosage:25 mg/kg; 50 mg/kg; 150 mg/kg
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Administration:p.o.; single dose
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Result:Led to more than 94% inhibition of pHER2 as early as 0.25 hours at 50 mg/kg, with inhibition maintained for 6 hours.
Led to 89% inhibition of pHER2 at 150 mg/kg, with the effect lasting for 24 hours.
Showed higher doses correlated with higher plasma exposure and more profound pHER2 inhibition in tumor tissue.
Ensayo clínico
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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No. CAS 2387570-00-3
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Appearance Solid
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Peso molecular 547.56
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Fòrmula C28H27F2N7O3
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Color Off-white to light yellow
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SMILES
COC1=CC2=C(C(NC3=CC=C(C(C)=C3)OC4=CC5=NC=NN5C=C4)=NC=N2)C(O[C@H]6CCN(CC6(F)F)C)=C1
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvente y solubilidad
In Vitro:
DMSO : 100 mg/mL (182.63 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: 2.5 mg/mL (4.57 mM); Clear solution; Need ultrasonic
This protocol yields a clear solution of 2.5 mg/mL.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: 2.5 mg/mL (4.57 mM); Clear solution; Need ultrasonic
This protocol yields a clear solution of 2.5 mg/mL.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Pureza y Documentación
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Ficha de datos (289 KB)
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SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
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Instrucciones de manejo (2659 KB)
Referencias
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.8263 mL | 9.1314 mL | 18.2628 mL | 45.6571 mL |
| 5 mM | 0.3653 mL | 1.8263 mL | 3.6526 mL | 9.1314 mL | |
| 10 mM | 0.1826 mL | 0.9131 mL | 1.8263 mL | 4.5657 mL | |
| 15 mM | 0.1218 mL | 0.6088 mL | 1.2175 mL | 3.0438 mL | |
| 20 mM | 0.0913 mL | 0.4566 mL | 0.9131 mL | 2.2829 mL | |
| 25 mM | 0.0731 mL | 0.3653 mL | 0.7305 mL | 1.8263 mL | |
| 30 mM | 0.0609 mL | 0.3044 mL | 0.6088 mL | 1.5219 mL | |
| 40 mM | 0.0457 mL | 0.2283 mL | 0.4566 mL | 1.1414 mL | |
| 50 mM | 0.0365 mL | 0.1826 mL | 0.3653 mL | 0.9131 mL | |
| 60 mM | 0.0304 mL | 0.1522 mL | 0.3044 mL | 0.7610 mL | |
| 80 mM | 0.0228 mL | 0.1141 mL | 0.2283 mL | 0.5707 mL | |
| 100 mM | 0.0183 mL | 0.0913 mL | 0.1826 mL | 0.4566 mL |
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