| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| Other Sizes |
|
Purity: ≥98%
ACC-789, also known as ZK-202650 and NVP-ACC789 is a novel, potent, selective and orally bioavailable inhibitor of human VEGFR-1, VEGFR-2 (mouse VEGFR-2), VEGFR-3 and PDGFR-β with IC50s of 0.38, 0.02 (0.23), 0.18, 1.4 μM, respectively. It is angiogenesis-dependent that tumors grow exponentially. Potent angiogenic inducers that work in concert both in vivo and in vitro are vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF).
| Targets |
VEGFR-2 (IC50 = 0.02 μM); VEGFR-1 (IC50 = 0.38 μM); mVEGFR-2 (IC50 = 0.23 μM); VEGFR-3 (IC50 = 0.18 μM); PDGFR-β (IC50 = 1.4 μM)
|
|---|---|
| ln Vitro |
NVP-ACC789 is an inhibitor of human VEGFR-1, VEGFR-2 (mouse VEGFR-2), VEGFR-3, and PDGFR-β, with IC50s of 0.38, 0.02 (0.23), 0.18, and 1.4 μM, respectively, according to the enzymatic kinase assays. When the VEGFR-2 inhibitor NVP-ACC789 is added to VEGF-treated cultures, the number of BME cells decreases from 1 μM to baseline levels. Similarly, NVP-ACC789 significantly suppresses bFGF-induced BME cell proliferation from 1 to 10 μM, but not to basal levels. With an IC50 of 1.6 nM, NVP-ACC789 is discovered to be a strong inhibitor of VEGF-induced HUVE cell proliferation. Additionally, NVP-ACC789 totally prevents BME and BAE cell invasion caused by VEGF as well as BAE cell invasion caused by VEGF-C. In both cell types, the inhibition is dose-dependent, reaching its maximum impact at 1 μM[1].
|
| ln Vivo |
Oral NVP-ACC789 administered once daily for six days inhibits VEGF-induced angiogenesis in a dose-dependent manner. While NVP-ACC789 does not have a linear dose-response curve, it does somewhat inhibit the response to bFGF[1].
|
| Enzyme Assay |
In 6-well plates, human VEGFR-2-transfected CHO cells are plated and allowed to grow to approximately 80% confluency. The cells are cultured in medium without fetal calf serum (FCS) for two hours at 37°C after serial dilutions of NVP-ACC789 are added. Then, 20 ng/mL of VEGF is added. Following a 5-minute incubation period at 37°C, the cells undergo two ice-cold phosphate-buffered saline washes before being lysed. Centrifugation is used to remove nuclei for 10 minutes at 4°C. It is determined how much protein is present in the lysates[1].
|
| Cell Assay |
It determines HUVE cell proliferation. 96-well plates coated with 1.5% gelatin are seeded with 5 x 103 cells per well. The cells are then incubated for 24 hours in endothelial cell growth medium that contains 5% fetal calf serum (FCS). After changing the medium, the cells are incubated for an additional 24 hours in essential basic medium (1.5% FCS). Once that is done, fresh medium containing either 0.5 ng/mL bFGF or 50 ng/mL VEGF is added to the essential basic media. Growth factors are added immediately after NVP-ACC789. Before adding the BrdU labeling solution, the cells are incubated for an additional twenty-four hours. After 24 hours, the labeling solution is eliminated, the cells are fixed, and incorporated BrdU is seen using TMB substrate and an anti-BrdU antibody labeled with peroxidase[1].
|
| Animal Protocol |
The dorsal flank of female mice is implanted subcutaneously with porous Teflon chambers (volume, 0.5 mL) containing 0.8% w/v agar-containing heparin (20 U/mL) with or without VEGF (2 μg/mL) or bFGF (0.3 μg/mL). The mice receive a daily oral dose of NVP-ACC789 or a vehicle (5% dimethyl sulfoxide, 1% Tween 80 in water) beginning the day before the chamber is implanted and lasting for an additional five days. The mice are put to death and the chambers are taken out at the conclusion of the treatment period. Carefully removed, the vascularized tissue growing around the chamber is weighed, and hemoglobin levels are used to determine the amount of blood present. It is calculated to find the percentage inhibition of the angiogenic response, which is an increase in tissue weight or blood volume. The dose response curves (% inhibition versus dose) are used to estimate EC50 values. Six animals per dose group participate in each experiment, and each dose is examined in a minimum of two separate studies[1].
|
| References |
| Molecular Formula |
C21H17BRN4
|
|---|---|
| Molecular Weight |
405.29048
|
| Exact Mass |
405.299
|
| Elemental Analysis |
C, 62.23; H, 4.23; Br, 19.71; N, 13.82
|
| CAS # |
300842-64-2
|
| Related CAS # |
300842-64-2
|
| Appearance |
Solid powder
|
| SMILES |
CC1=C(C=C(C=C1)NC2=NN=C(C3=CC=CC=C32)CC4=CC=NC=C4)Br
|
| InChi Key |
GXWKSXUPEFVUOO-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C21H17BrN4/c1-14-6-7-16(13-19(14)22)24-21-18-5-3-2-4-17(18)20(25-26-21)12-15-8-10-23-11-9-15/h2-11,13H,12H2,1H3,(H,24,26)
|
| Chemical Name |
N-(3-bromo-4-methylphenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine
|
| Synonyms |
ZK-202650; ZK 202650; ZK202650; NVP-ACC789; NVP-ACC 789; NVP-ACC-789; ACC-789; ACC 789; ACC789
|
| 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: ~25 mg/mL (~61.7 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.17 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 25.0 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: ≥ 2.5 mg/mL (6.17 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4674 mL | 12.3368 mL | 24.6737 mL | |
| 5 mM | 0.4935 mL | 2.4674 mL | 4.9347 mL | |
| 10 mM | 0.2467 mL | 1.2337 mL | 2.4674 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
COA