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.
For research use only. We do not sell to patients.
- Purity : 99.62%
- CAS No.: 2387570-00-3
- Formula: C28H27F2N7O3
- Molecular Weight:547.56
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Storage: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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Biological Activity
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Chemical Information
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Solvent & Solubility
- Protocols
- Purity & Documentation
- References
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Help & FAQs
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Biological Activity
Description
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. Further protocols information, click here.
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.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 2387570-00-3
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Appearance Solid
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Molecular Weight 547.56
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Formula 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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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvent & Solubility
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.
Protocols
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How to Select the Route of Administration for Mammals
Route-of-administration selection in mammals is a pharmacokinetic, pharmacodynamic, formulation, animal-welfare, and translational decision, not a default technical choice. The selected route should match the study goal: intravenous dosing is most useful when complete systemic exposure and rapid onset are required, oral dosing is most translational for orally intended medicines but is affected by absorption and first-pass metabolism, subcutaneous or intramuscular dosing can provide slower systemic exposure, and intraperitoneal dosing can be useful in rodent proof-of-concept studies but may have limited clinical translation. Published route-comparison studies show that the same compound can produce different exposure, onset, bioavailability, tissue distribution, and tolerability depending on route; therefore, route choice should be supported by pilot pharmacokinetic or pharmacodynamic evidence when the literature is insufficient. Unresolved questions include how to standardize route sel
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Patient-Derived Xenograft (PDX)
Patient-derived xenograft (PDX) models are generated by engrafting primary human tumor tissue directly into immunodeficient mice, allowing in vivo propagation of patient tumor biology without initial in vitro adaptation. These models are used to preserve key histopathological and molecular characteristics of the original tumor and enable assessment of tumor growth dynamics and therapeutic response in a living organism. The biological readout is tumor engraftment and subsequent growth in the murine host, which reflects the ability of human tumor cells to survive, vascularize, and expand in an immunocompromised microenvironment.
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Transepithelial/transendothelial electrical resistance assay
TEER measures electrical resistance across epithelial or endothelial monolayers cultured on permeable supports, and the readout reflects ionic conductance through the cell barrier, especially the paracellular pathway regulated by junctional integrity. TEER can be measured without destroying the monolayer and is commonly used before or during transport, permeability, barrier-disruption, and barrier-maturation experiments. TEER values are influenced by biological maturation and technical conditions; reported factors include temperature, medium formulation, passage number, electrode geometry, membrane properties, and junctional length during early monolayer maturation. Therefore, TEER should be interpreted with blank-insert subtraction, area normalization, repeated readings, and, when possible, orthogonal barrier readouts such as FITC-dextran flux or tight-junction staining.
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Patient-Derived Orthotopic Xenograft (PDOX)
Patient-derived orthotopic xenograft (PDOX) modeling implants fresh patient tumor tissue or patient-derived tumor cells into the anatomically corresponding organ or tissue site of immunodeficient mice, usually by surgical orthotopic implantation, to preserve patient tumor histology, local microenvironmental context, invasion, metastatic behavior, and treatment-response features better than subcutaneous implantation. PDOX readouts include tumor engraftment, orthotopic tumor growth, local invasion, metastasis, recurrence after resection, histologic similarity to the donor tumor, biomarker retention, molecular concordance, survival, and response or resistance to therapy. PDOX models are used for preclinical drug testing and individualized therapy evaluation, but engraftment success varies by tumor type and specimen quality.
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Splenic/Portal-Vein Liver Metastasis Xenograft
Splenic and portal-vein liver metastasis xenograft models deliver tumor cells into the portal circulation so that cells reach the liver first and form hepatic metastatic lesions; splenic injection uses the spleen as an access route to the portal system, while direct portal-vein injection introduces cells into the portal vein without requiring splenectomy. The assay detects liver colonization, intrahepatic tumor growth, tumor distribution, treatment response, survival, and liver-metastasis microenvironment changes; readouts include bioluminescence or fluorescence imaging, gross liver nodule counts, liver weight or tumor burden, histology, and survival.
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Subcutaneous Cell-Line-Derived Xenograft
Subcutaneous cell-line-derived xenograft (CDX) models are established by implanting cultured human cancer cell lines into immunodeficient mice, where the injected cells form localized tumors that can be monitored in vivo as a measure of tumorigenic potential, growth kinetics, and treatment response. These models are widely used in oncology research because they allow reproducible tumor formation and enable comparative assessment of tumor growth between different cell lines or genetic manipulations in a controlled in vivo microenvironment. Subcutaneous implantation of cancer cells in immunodeficient mice is a standard approach for evaluating tumor growth behavior and therapeutic response across multiple cancer types, including prostate, esophageal, pancreatic, and colon cancer models.
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Breast Cancer Modeling
Breast cancer is a heterogeneous cancer, and it has been distinguished into four subtypes: luminal A, luminal B, HER2-positive and basal-like. Molecular mutations, epigenetic alterations, hormone exposure and immune microenvironment are related to the progression of breast cancer.
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Orthotopic Cell-Line Xenograft
Orthotopic cell-line xenograft models involve implantation of human cancer cell lines into the anatomically corresponding organ of immunodeficient mice to reproduce tumor growth within a native microenvironment, enabling more clinically relevant tumor behavior compared with subcutaneous models. These models are widely used because orthotopic placement better recapitulates tumor progression, including invasion and metastatic spread, which are often underrepresented in heterotopic implantation systems. Compared with conventional xenografts, orthotopic implantation is described as more technically complex but provides improved simulation of tumor-microenvironment interactions and metastatic behavior, making it particularly valuable for translational oncology research. Surgical orthotopic implantation approaches have been emphasized as enabling faithful reproduction of clinical cancer features, including metastasis and disease progression patterns that align with the tumor’s organ of origi
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Intraperitoneal/Peritoneal Dissemination Xenograft
Intraperitoneal (IP) or peritoneal dissemination xenograft models are based on the introduction of human cancer cells into the peritoneal cavity of immunodeficient mice, where they attach to peritoneal surfaces, form multicellular aggregates or spheroids, and progressively generate disseminated tumor nodules that mimic advanced peritoneal metastatic disease. These models are widely used to study ovarian cancer progression, tumor-microenvironment interactions, and intraperitoneal therapeutic responses, often incorporating bioluminescence or fluorescence imaging to longitudinally monitor tumor burden in vivo. The biological principle relies on the capacity of tumor cells such as SKOV3 or related ovarian carcinoma lines to survive in suspension, aggregate within ascites-like fluid, adhere to mesothelial surfaces, and invade peritoneal organs, thereby recapitulating human peritoneal carcinomatosis patterns observed in advanced disease.
Purity & Documentation
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Data Sheet (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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Handling Instructions (2659 KB)
References
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 |
DZD1516 Related Classifications
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