| Size | Price | |
|---|---|---|
| 100mg | ||
| 250mg | ||
| 500mg |
| ln Vitro |
GZD856 (0.0032-10 μM, 72 hours) shows anti-proliferative action on a panel of lung cancer cells [1]. GZD856 (0.3-3 μM; 24-28 hours) promotes dose-dependent G0/G1 arrest and death in H1703 cells but not in A549 cells [1]. GZD856 (0.1-10 μM; 6 hours) dose-dependently suppresses PDGFRα/β phosphorylation and downstream signaling in H1703 and A549 cells [1]. GZD856 reduces the growth of K562, K562R (Q252H) and mouse Ba/F3 cells ectopically expressing Bcr-AblWT and Bcr-AblT315I, with IC50 of 2.2, 67.0, 0.64 and 10.8 nM correspondingly [2].
|
|---|---|
| ln Vivo |
In both the H1703 and A549 lung cancer models, GZD856 (10–30 mg/kg, orally, once day for 16 days) had good anti-tumor effectiveness and was well tolerated. In the A549-Luc orthotopic model, GZD856 prevents lung cancer cells from metastasizing to the brain and liver [1]. Xenografts of K562 and Ba/F3 cells expressing Bcr-AblT315I can successfully suppress tumor growth in mice bearing GZD856 (10 mg/kg; orally once daily for 8 days) [2]. In rats, GZD856 (5 mg/kg; single intravenous injection) had an optimum plasma exposure (Cmax=934.38 μg/L), a lengthy half-life (T1/2=19.97 h), and an AUC0-∞ (8165.8 μg/L· h) [1]. In rats, GZD856 (25 mg/kg; single oral dose) has a good degree of oral bioavailability (BA=78%), an optimal plasma exposure (Cmax=899.5 μg/L), and a lengthy half-life (T1/2=22.2 h] [1].
|
| Cell Assay |
Cell Viability Assay[1]
Cell Types: H1703, A549, Calu-6, 95-D, L-78, HCC827, SPCA-1, H1650, H1299, H522, H332 and H820 NSCLC Cell Tested Concentrations: 0.0032-10 μM Incubation Duration: 72 hrs (hours) Experimental Results: Inhibition of PDGFRα overexpression in H1703 cells, IC50 is 0.25 μM. Apoptosis analysis [1] Cell Types: H1703 and A549 NSCLC Cell Tested Concentrations: 0.3, 1, 3 μM Incubation Duration: 24, 48 hrs (hours) Experimental Results: At a concentration of 3.0 μM, the apoptosis rate of H1703 cells was 54.1%; Only 15.5% were observed in A549 cells under similar conditions. Reduces CDK4, cyclin D2, CDK2 and cyclin E protein levels and activates PARP and Caspase-3 cleavage in H1703 cells. Western Blot Analysis[1] Cell Types: H1703 and A549 NSCLC Cell Tested Concentrations: 0.1-10 μM Incubation Duration: 6 hrs (hours) Experimental Results: Inhibited the phosphorylation of PDGFRα and PDGFRβ in a dose-dependent manner. The activation of downstream AKT, ERK1/2 and STAT3 was observed and had no significant effect on the total protein level. |
| Animal Protocol |
Animal/Disease Models: Male CB17-SCID (severe combined immunodeficient) mouse implanted with H1703 and A549 cancer cells [1]
Doses: 10, 30 mg/kg Route of Administration: po (oral gavage), one time/day for 16 days Experimental Results: In H1703 xenograft mice It demonstrated anti-tumor effect and inhibited tumor growth. When the doses were 10 and 30 mg/kg, the TGI values were 20.8% and 74.1% respectively. Antitumor effects were demonstrated in A549 xenograft mice, with a TGI value of 51.1% at 30 mg/kg. All test groups were well tolerated, with no deaths or significant weight loss. Animal/Disease Models: SD (SD (Sprague-Dawley)) rat (180-220 g) [1] Doses: 5 mg/kg IV; 25 mg/kg po (pharmacokinetic/PK/PK analysis) Route of Administration: Single IV and Oral Experimental Results: Iv: T1/2=19.97 h; Cmax=934.38 μg/L; AUC0-∞=8165.8 μg/L·h. Po: T1/2=22.2 hrs (hrs (hours)); Cmax=899.5μg/L; BA=78%. |
| References |
[1]. Zhang Z, et al. GZD856, a novel potent PDGFRα/β inhibitor, suppresses the growth and migration of lung cancer cells in vitro and in vivo. Cancer Lett. 2016 May 28;375(1):172-178.
[2]. Lu X, et al. Synthesis and identification of GZD856 as an orally bioavailable Bcr-AblT315I inhibitor overcoming acquired imatinib resistance. J Enzyme Inhib Med Chem. 2017 Dec;32(1):331-336. |
| Molecular Formula |
C29H27F3N6O
|
|---|---|
| Molecular Weight |
532.559496164322
|
| CAS # |
1257628-64-0
|
| Related CAS # |
GZD856 formic;2804039-78-7
|
| Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
|
| SMILES |
FC(C1C=C(C=CC=1CN1CCN(C)CC1)NC(C1C=CC(C)=C(C#CC2C=NC3=CC=NN3C=2)C=1)=O)(F)F
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~250 mg/mL (~469.43 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.91 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 (3.91 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8777 mL | 9.3886 mL | 18.7772 mL | |
| 5 mM | 0.3755 mL | 1.8777 mL | 3.7554 mL | |
| 10 mM | 0.1878 mL | 0.9389 mL | 1.8777 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
