TG 100572
Modify Date: 2024-01-07 23:02:22
TG 100572 structure
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Common Name | TG 100572 | ||
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| CAS Number | 867334-05-2 | Molecular Weight | 475.97000 | |
| Density | N/A | Boiling Point | N/A | |
| Molecular Formula | C26H26ClN5O2 | Melting Point | N/A | |
| MSDS | N/A | Flash Point | N/A | |
Use of TG 100572TG 100572 is a multi-targeted kinase inhibitor which inhibits receptor tyrosine kinases and Src kinases; has IC50s of 2, 7, 2, 16, 13, 5, 0.5, 6, 0.1, 0.4, 1, 0.2 nM for VEGFR1, VEGFR2, FGFR1, FGFR2, PDGFRβ, Fgr, Fyn, Hck, Lck, Lyn, Src, Yes, respectively. |
| Name | 4-chloro-3-[5-methyl-3-[4-(2-pyrrolidin-1-ylethoxy)anilino]-1,2,4-benzotriazin-7-yl]phenol |
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| Synonym | More Synonyms |
| Description | TG 100572 is a multi-targeted kinase inhibitor which inhibits receptor tyrosine kinases and Src kinases; has IC50s of 2, 7, 2, 16, 13, 5, 0.5, 6, 0.1, 0.4, 1, 0.2 nM for VEGFR1, VEGFR2, FGFR1, FGFR2, PDGFRβ, Fgr, Fyn, Hck, Lck, Lyn, Src, Yes, respectively. |
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| Related Catalog | |
| Target |
VEGFR1:2 nM (IC50) VEGFR2:7 nM (IC50) FGFR1:2 nM (IC50) FGFR2:16 nM (IC50) PDGFRβ:13 nM (IC50) |
| In Vitro | TG 100572 shows sub-nanomolar activity against the Src family as well as RTK such as VEGFR1 and R2, FGFR1 and R2, and PDGFRβ. TG 100572 inhibits vascular endothelial cell proliferation (ED50=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[1]. TG 100572 is shown to inhibit hRMVEC cell proliferation, with an IC50 of 610±72 nM. This suggests that TG 100572 has the therapeutic potential to inhibit VEGF function in ocular endothelial cells, a contributing factor to pathological angiogenesis in diseases such as AMD and PDR[2]. |
| In Vivo | Systemic delivery of TG 100572 in a murine model of laser-induced choroidal neovascularization (CNV) causes significant suppression of CNV, but with an associated weight loss suggestive of systemic toxicity[1]. A concentration of 23.4 µM (Cmax) of TG 100572 is reached in 30 min (Tmax)=0.5 h) in the choroid and the sclera. However, the levels of TG 100572 in the retina are relatively low. The half-life of TG 100572 in ocular tissues is very short; hence, the compound is administered topically minimum t.i.d. to maintain appropriate drug levels in the eye. The maximum concentration one can achieve in formulations using TG 100572 is 0.7% w/v[2]. |
| Cell Assay | For proliferation assays, human retinal microvascular EC plated in 96-well cluster plates are cultured for 48 hr in the presence of either TG 100572 (2 nM-5 µM) or DMSO; medium contained 10% FBS, 50 µg/mL heparin, and 50 ng/mL rhVEGF. Cell numbers are then assessed using an XTT-based assay[1]. |
| Animal Admin | Mice: C57BL/6 mice (15-20 g) are dosed i.p. twice daily for 4 days with 5 mg/ kg TG 100572, followed by a single dose on Day 5, 5 hr after which plasma samples are taken, animals euthanized, and eyes explanted. Alternatively, mice are dosed topically with either TG 100572 or related prodrugs (e.g., TG 100801) by delivering a single 10 µL drop to both eyes for a total of two days, and both plasma and eyes harvested prior to or 0.5, 1, 3, 5, or 7 hr after the Day 2 dosing[1]. |
| References |
| Molecular Formula | C26H26ClN5O2 |
|---|---|
| Molecular Weight | 475.97000 |
| Exact Mass | 475.17800 |
| PSA | 83.40000 |
| LogP | 5.58830 |
|
~85%
TG 100572 CAS#:867334-05-2 |
| Literature: Palanki, Moorthy S. S.; Akiyama, Hideo; Campochiaro, Peter; Cao, Jianguo; Chow, Chun P.; Dellamary, Luis; Doukas, John; Fine, Richard; Gritzen, Colleen; Hood, John D.; Hu, Steven; Kachi, Shu; Kang, Xinshan; Klebansky, Boris; Kousba, Ahmed; Lohse, Dan; Chi, Ching Mak; Martin, Michael; McPherson, Andrew; Pathak, Ved P.; Renick, Joel; Soll, Richard; Umeda, Naoyasu; Yee, Shiyin; Yokoi, Katsutoshi; Zeng, Binqi; Zhu, Hong; Noronha, Glenn Journal of Medicinal Chemistry, 2008 , vol. 51, # 6 p. 1546 - 1559 |
|
~72%
TG 100572 CAS#:867334-05-2 |
| Literature: Cao, Jianguo; Fine, Richard; Gritzen, Colleen; Hood, John; Kang, Xinshan; Klebansky, Boris; Lohse, Dan; Mak, Chi Ching; McPherson, Andrew; Noronha, Glenn; Palanki, Moorthy S.S.; Pathak, Ved P.; Renick, Joel; Soll, Richard; Zeng, Binqi; Zhu, Hong Bioorganic and Medicinal Chemistry Letters, 2007 , vol. 17, # 21 p. 5812 - 5818 |
![1,2,4-Benzotriazin-3-amine, 7-(2-chloro-5-Methoxyphenyl)-5-Methyl-N-[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]- structure](https://www.chemsrc.com/caspic/024/867331-63-3.png)
![1-[2-(4-Bromophenoxy)ethyl]pyrrolidine structure](https://www.chemsrc.com/caspic/084/1081-73-8.png)
| Precursor 3 | |
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| DownStream 0 | |
| cs-0783 |
| TG 100572 |