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| Targets |
GW2974 targets epidermal growth factor receptor (EGFR/ErbB-1) and ErbB-2 (HER2) receptor tyrosine kinases. These receptors are members of the ErbB family and are frequently overexpressed or mutated in various cancers, driving tumor cell proliferation, survival, and invasion. GW2974 is a dual inhibitor with IC50 values of 0.007 μM for EGFR and 0.016 μM for HER2. By inhibiting these kinases, the compound blocks downstream signaling pathways including MAPK and PI3K/AKT.
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| ln Vitro |
After being treated for 24 hours at 0.5–5 μM, GW2974 (0.5–50 μM, 3 hours) can reduce the growth of U87MG and U251MG cells and has evident cytotoxicity at 10 μM or above [1]. GW2974 (0.001-100 μM, 24 hours): There is a dose-related relationship between GW2974's effects on GBM cells and migration [1]. GW2974 (0.001-100 μM, 24 hours) prevents HN5, N87, and BT474 cells from proliferating[2]. Results: Cell viability of U87MG and U251MG in 0.5 μM and 5 μM was reduced to 89.4% and 86.3%, respectively, compared to the control. Strain: U87MG, U251MG Concentration: 0.5-50 μM Incubation time: 3 hours. An experiment on cell proliferation [1]
In vitro, GW2974 demonstrates potent inhibitory activity against EGFR and HER2 with IC50 values of 0.007 μM and 0.016 μM, respectively. The compound suppresses the growth of tumor cells. It has in vitro inhibitory activity against the kinase domains of EGFR and HER2. These properties make GW2974 a valuable tool for studying EGFR/HER2 signaling and evaluating dual EGFR/HER2 inhibition as a therapeutic strategy. |
| ln Vivo |
Low doses of GW2974 (30 mg/kg, 100 mg/kg, model, once daily) have an effect on the growth of angiogenic tumor cells and intravascular tumor growth in GBM tumors; however, in the HN5 human tumor xenograft model, high doses of GW2974 (10 mg/kg, 30 mg/kg, facial dose, twice daily) and BT474 completely eliminated the tumor inhibition effect of low-dose GW2974 [1]. In human tumor xenograft mouse models, it dramatically and dose-dependently suppressed tumor growth [2].
In vivo, GW2974 is orally active. It suppresses the invasion and tumor growth of glioblastoma (GBM) cells in vivo. The compound's oral bioavailability and efficacy in GBM models support its use in cancer research. Specific animal study protocols and dosing regimens are available in the primary literature but are not detailed in the available sources. |
| Enzyme Assay |
Not specifically documented for GW2974. For kinase inhibitors, cell-free enzyme assays typically measure the inhibition of EGFR and HER2 kinase activity using purified enzyme preparations and peptide or protein substrates. Radiolabeled ATP or fluorescence-based detection methods are used to quantify kinase activity. IC50 values (0.007 μM for EGFR, 0.016 μM for HER2) are determined from concentration-response curves.
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: U87MG, U251MG Tested Concentrations: 0.5-50 μM Incubation Duration: 3 hrs (hours) Experimental Results: Compared to the control, U87MG and U251MG cell viability in 0.5 μM and 5 μM was diminished to 89.4% and 86.3%, respectively. Cell proliferation experiment [1] Cell Types: U87MG, U251MG Tested Concentrations: 0.5-5 μM Incubation Duration: 24 h Experimental Results: 0.5 μM and 5 μM inhibited the proliferation of U87MG and U251MG cells. Cell invasion analysis [1] Cell Types: U87MG, U251MG Tested Concentrations: 0.5-5 μM Incubation Duration: 24 h Experimental Results: The percentages of U87MG and U251MG cells in 0.5 μM were diminished to 55.6% and 48.6% respectively. Cell migration assay [1] Cell Types: U87MG, U251MG Tested Concentrations: 0.5-5 μM Incubation Duration: 24 h Experimental Results: At 0.5 μM, the relative migration distance (percentage) of U87MG and U251MG cells was diminished to 40.2% and 51.6% respectively. Compared with the control, the relative migration distance of U87MG and U251MG cells was 5 μM. Cell proliferation assay [2] Cell Types: BT474, HN In vitro cell-based assays for GW2974 include cell proliferation and survival assays in cancer cell lines with EGFR/HER2 overexpression or mutations. Signaling pathway analysis by Western blot can assess inhibition of EGFR/HER2 phosphorylation and downstream effectors such as MAPK and AKT. Invasion assays may evaluate the effect of the compound on tumor cell invasiveness. Concentration ranges typically span from nanomolar to micromolar. |
| Animal Protocol |
Animal/Disease Models: GBM xenograft mouse model [1]
Doses: 30 mg/kg, 100 mg/kg Route of Administration: po (oral gavage) Experimental Results: Tumor growth slowed down at doses of 30 mg/kg and 100 mg/kg . The 30 mg/kg group inhibited the invasion of the area around the tumor, but the 100 mg/kg group demonstrated enhanced tumor invasion in the brain tissue. Doses of 30 mg/kg and 100 mg/kg inhibited angiogenesis. Animal/Disease Models: CD-1 nude mice (HN5), CB-17 SCID (severe combined immunodeficient) mouse (BT474) [2] Doses: 10 mg/kg, 30 mg/kg Route of Administration: po (oral gavage) Experimental Results: Inhibition of HN5 model The therapeutic dose for tumor growth is 30 mg/kg. A therapeutic dose of 10 mg/kg inhibited tumor growth by approximately 95% in the HN5 model and approximately 50% in the BT474 model. In vivo studies with GW2974 are conducted in mouse models of glioblastoma and other EGFR/HER2-driven cancers. The compound is administered orally due to its oral bioavailability. Endpoints include tumor growth inhibition, assessment of invasion, and evaluation of signaling pathway inhibition in tumor tissues. Dosing regimens are detailed in the primary literature. |
| ADME/Pharmacokinetics |
GW2974 is orally active, indicating favorable oral bioavailability. As a small molecule with molecular weight 395.46 and formula C23H22N8? (exact formula not verified), it is suitable for oral administration. The compound appears as a yellow solid with purity ≥98%. Detailed PK parameters such as half-life, Cmax, and AUC are available in the primary literature but are not detailed in the available sources.
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| Toxicity/Toxicokinetics |
Specific toxicity data for GW2974 are not provided in the available literature. As a research compound, it is not intended for human therapeutic use. Standard laboratory safety precautions should be followed when handling this compound. The compound is supplied for research purposes only.
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| References |
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| Additional Infomation |
N6,N6-dimethyl-N4-[1-(benzyl)-5-indazolyl]pyrido[3,4-d]pyrimidine-4,6-diamine is a pyridopyrimidine.
GW2974 has the IUPAC name 4-N-(1-benzylindazol-5-yl)-6-N,6-N-dimethylpyrido[3,4-d]pyrimidine-4,6-diamine. It is a potent dual inhibitor of EGFR and HER2. The compound is used in glioblastoma (GBM) research and is a featured product for Kinase Phosphatase Biology research. |
| Molecular Formula |
C23H21N7
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| Molecular Weight |
395.47
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| Exact Mass |
395.186
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| CAS # |
202272-68-2
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| PubChem CID |
6603857
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| Appearance |
Light yellow to yellow solid powder
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| Boiling Point |
645.6ºC at 760 mmHg
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| Flash Point |
344.3ºC
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| Vapour Pressure |
1.47E-16mmHg at 25°C
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| Index of Refraction |
1.71
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| LogP |
4.305
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
30
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| Complexity |
552
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
DYYZXRCFCVDSKD-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H21N7/c1-29(2)22-11-19-20(13-24-22)25-15-26-23(19)28-18-8-9-21-17(10-18)12-27-30(21)14-16-6-4-3-5-7-16/h3-13,15H,14H2,1-2H3,(H,25,26,28)
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| Chemical Name |
4-N-(1-benzylindazol-5-yl)-6-N,6-N-dimethylpyrido[3,4-d]pyrimidine-4,6-diamine
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| Synonyms |
GW 2974; GW-2974; GW2974
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5286 mL | 12.6432 mL | 25.2864 mL | |
| 5 mM | 0.5057 mL | 2.5286 mL | 5.0573 mL | |
| 10 mM | 0.2529 mL | 1.2643 mL | 2.5286 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.
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