| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
|
||
| 25mg |
|
||
| 50mg | |||
| 100mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
VEGFR1 (IC50 = 2 nM); VEGFR2 (IC50 = 7 nM); FGFR1 (IC50 = 2 nM); FGFR2 (IC50 = 16 nM); PDGFRβ (IC50 = 13 nM)
TG 100572 HCl is a multi-targeted kinase inhibitor that targets VEGFR1, VEGFR2, FGFR1, FGFR2, PDGFRβ, and Src family kinases (Fgr, Fyn, Hck, Lck, Lyn, Src, Yes). The IC50 values for these targets are: VEGFR1 (2 nM), VEGFR2 (7 nM), FGFR1 (2 nM), FGFR2 (16 nM), PDGFRβ (13 nM), Fgr (5 nM), Fyn (0.5 nM), Hck (6 nM), Lck (0.1 nM), Lyn (0.4 nM), Src (1 nM), and Yes (0.2 nM). |
|---|---|
| ln Vitro |
Subnanomolar action is demonstrated by TG 100572 HCl against the Src family and RTKs, including VEGFR1 and R2, FGFR1 and R2, and PDGFRβ. The hydrochloric acid TG 100572 inhibits the reproduction of vascular endothelial cells (ED50=610±71 nM) and prevents the phosphorylation of extracellular signals that regulate telogen. With an IC50 of 610±72 nM, TG 100572 Hydrochronide suppresses the growth of hRMVEC cells. This implies that TG 100572 Hydrochronide may be able to prevent ocular endothelial cells—which are the starting points for aberrant angiogenesis in conditions like AMD and PDR—from functioning as VEGF [2].
TG 100572 HCl shows sub-nanomolar activity against the Src family kinases as well as RTKs such as VEGFR1, VEGFR2, FGFR1, FGFR2, and PDGFRβ. It inhibits vascular endothelial cell proliferation with an ED50 of 610±71 nM and blocks VEGF-induced phosphorylation of extracellular signal-regulated kinase. TG 100572 induces apoptosis in rapidly proliferating, but not quiescent, endothelial cell cultures. The compound inhibits hRMVEC cell proliferation with an IC50 of 610±72 nM. These findings suggest therapeutic potential to inhibit VEGF function in ocular endothelial cells. |
| ln Vivo |
In a laser-induced choroidal neovascularization (CNV) model, systemic intravenous TG 100572 Hydrochronide can significantly inhibit CNV; however, weight loss suggests systemic toxicity [1]. Within half an hour, the concentration of TG 100572 Hydrochronide in the choroid and sclera reaches 23.4 μM (Cmax) (Tmax) = 0.5 h. On the other hand, there wasn't much TG 100572 hydrochloride in the acceleration. Because TG 100572 hydrochloride has a brief half-life in ocular tissue, it must be applied topically with little time interval in order to keep the right amount of medication in the eye. TG 100572 Hydrochloride formulations can achieve a maximum concentration of 0.7% w/v[2].
In a murine model of laser-induced choroidal neovascularization (CNV), systemic delivery of TG 100572 causes significant suppression of CNV. A concentration of 23.4 μM (Cmax) of TG 100572 is reached in 30 minutes (Tmax=0.5 h) in the choroid and sclera; however, levels in the retina are relatively low. The half-life of TG 100572 in ocular tissues is very short; hence, the compound needs to be administered topically at least three times daily to maintain appropriate drug levels in the eye. Systemic delivery is associated with weight loss, suggestive of systemic toxicity. |
| Enzyme Assay |
The kinase inhibition assay for TG 100572 involves incubating the compound with recombinant kinases in the presence of ATP and a substrate. The reaction is carried out in a buffer optimized for each kinase (e.g., 50 mM HEPES, pH 7.5, 10 mM MgCl2, 1 mM EGTA, 0.01% Brij-35). After incubation at room temperature for 30-60 minutes, the reaction is stopped, and the amount of phosphorylated substrate is quantified using a luminescence-based kinase assay (e.g., ADP-Glo) or HTRF. Dose-response curves are generated using at least 8 concentrations of the compound in duplicate, and IC50 values are calculated using nonlinear regression analysis.
|
| Cell Assay |
In order to perform proliferation assays, human retinal microvascular EC plated in 96-well cluster plates are cultured for 48 hours with 10% FBS, 50 µg/mL heparin, and 50 ng/mL rhVEGF in the presence of either TG 100572 (2 nM–5 µM) or DMSO. After that, an XTT-based assay is used to determine the number of cells[1].
Human retinal microvascular endothelial cells (hRMVECs) are seeded in 96-well plates coated with fibronectin and grown in endothelial growth medium containing VEGF. Cells are treated with varying concentrations of TG 100572 HCl (e.g., 0.1 nM to 10 μM) for 72 hours. Cell proliferation is measured using a colorimetric assay such as WST-1 or MTS. The IC50 for inhibition of proliferation is calculated. Apoptosis is assessed using an annexin V-FITC apoptosis detection kit, followed by flow cytometry analysis to determine the percentage of apoptotic cells. |
| Animal Protocol |
Mice: C57BL/6 mice (15–20 g) are given 5 mg/kg TG 100572 intraperitoneally (i.p.) twice a day for 4 days. On Day 5, 5 hours later, a single dose is given, plasma samples are collected, the animals are put to sleep, and their eyes are removed. As an alternative, mice receive a single 10 µL drop applied topically to each eye for a total of two days, either with TG 100572 or related prodrugs (e.g., TG 100801), and both the eyes and plasma are harvested before or 0.5, 1, 3, 5, or 7 hours after the Day 2 dosing[1].
The in vivo efficacy of TG 100572 is evaluated in a murine model of laser-induced choroidal neovascularization (CNV). C57BL/6 mice undergo laser photocoagulation to induce CNV. TG 100572 is administered systemically (e.g., intraperitoneally or orally) or topically as eye drops. After treatment for a specified period (e.g., 7 days), the area of CNV is measured in choroidal flat mounts using fluorescent staining. The percentage inhibition of CNV is calculated relative to vehicle-treated controls. Body weight is monitored as an indicator of systemic toxicity. |
| ADME/Pharmacokinetics |
In a murine model of laser-induced CNV, a concentration of 23.4 μM (Cmax) of TG 100572 is reached in 30 min (Tmax=0.5 h) in the choroid and sclera. However, levels in the retina are relatively low. The half-life of TG 100572 in ocular tissues is very short; therefore, the compound must be administered topically at least three times daily to maintain appropriate drug levels in the eye. The maximum concentration achievable in formulations using TG 100572 is 0.7% w/v.
|
| Toxicity/Toxicokinetics |
In a murine model of laser-induced CNV, systemic delivery of TG 100572 causes significant suppression of CNV but is associated with weight loss suggestive of systemic toxicity. The compound is intended for research use only and is not approved for human therapeutic applications. Standard safety precautions should be followed when handling this compound, including the use of appropriate personal protective equipment.
|
| References |
|
| Additional Infomation |
TG 100572 HCl is a multi-targeted kinase inhibitor that inhibits receptor tyrosine kinases and Src kinases. It has IC50 values of 2, 7, 2, 16, 13, 5, 0.5, 6, 0.1, 0.4, 1, and 0.2 nM for VEGFR1, VEGFR2, FGFR1, FGFR2, PDGFRβ, Fgr, Fyn, Hck, Lck, Lyn, Src, and Yes, respectively. The compound is supplied for laboratory research purposes and is stored at -80°C for long-term stability.
|
| Molecular Formula |
C26H27CL2N5O2
|
|---|---|
| Molecular Weight |
512.43088
|
| Exact Mass |
511.154
|
| Elemental Analysis |
C, 60.94; H, 5.31; Cl, 13.84; N, 13.67; O, 6.24
|
| CAS # |
867331-64-4
|
| Related CAS # |
TG 100572;867334-05-2
|
| PubChem CID |
24823567
|
| Appearance |
Pink to red solid powder
|
| LogP |
6.39
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
35
|
| Complexity |
630
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
Cl.ClC1C(C2C=C(C)C3C(=NN=C(NC4C=CC(OCCN5CCCC5)=CC=4)N=3)C=2)=CC(O)=CC=1
|
| InChi Key |
NVINBIHNVAYEND-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C26H26ClN5O2.ClH/c1-17-14-18(22-16-20(33)6-9-23(22)27)15-24-25(17)29-26(31-30-24)28-19-4-7-21(8-5-19)34-13-12-32-10-2-3-11-32;/h4-9,14-16,33H,2-3,10-13H2,1H3,(H,28,29,31);1H
|
| Chemical Name |
4-chloro-3-[5-methyl-3-[4-(2-pyrrolidin-1-ylethoxy)anilino]-1,2,4-benzotriazin-7-yl]phenol;hydrochloride
|
| Synonyms |
TG100572 HCl; TG 100572; TG100572; TG-100572 HCl
|
| 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 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)
|
| Solubility (In Vitro) |
DMSO: ~25 mg/mL (~48.8 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.88 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 25.0 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 | 1.9515 mL | 9.7574 mL | 19.5149 mL | |
| 5 mM | 0.3903 mL | 1.9515 mL | 3.9030 mL | |
| 10 mM | 0.1951 mL | 0.9757 mL | 1.9515 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.
 TG100572 inhibits VEGF signaling and induces apoptosis in proliferating vascular endothelial cells.
Fluorescein leakage after topical delivery of TG100801 in a rat model of retinal vein occlusion.J Cell Physiol.2008 Jul;216(1):29-37. |
|---|
 Systemic delivery of TG100572 in a murine model of choroidal neovascularization (CNV).J Cell Physiol.2008 Jul;216(1):29-37. |
 Ocular distribution of14C-TG100801 following topical instillation in the rabbit.
Topical delivery of TG100801 in a murine model of choroidal neovascularlization (CNV).J Cell Physiol.2008 Jul;216(1):29-37 |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
