TG 100801 - 98%, high purity , Vascular endothelial growth factor receptor 2 inhibitor, CAS No.867331-82-6, Vascular endothelial growth factor receptor 2 inhibitor

Item Number

T647871

• Synonyms: 1VZO7A0J9S | CS-0785 | MS-30410 | A916109 | CID 11973736 | SCHEMBL12198196 | TG100801 | TG-100801 | TG100-801 | DB05075 | F84838 | NSC800948 | NSC-800948 | AKOS016008711 | TG 100801 | AKOS030526767 | GOSERELIN [EP MONOGRAPH] | UNII-1VZO7A0J9S | [4-chloro-
• Specifications & Purity: ≥98%
• Biochemical and Physiological Mechanisms: TG 100801 is a proagent that generates TG 100572 by de-esterification in development to treat age-related macular degeneration. TG 100572 is a multi-targeted kinase inhibitor which inhibits receptor tyrosine kinases and Src kinases ; has IC 50 s of 2, 7,
• Storage Temp: Store at -20°C
• Shipped In: Ice chest + Ice pads
• Action Type: INHIBITOR
• Mechanism of action: Vascular endothelial growth factor receptor 2 inhibitor

Product Description

TG 100801 is a proagent that generates TG 100572 by de-esterification in development to treat age-related macular degeneration. TG 100572 is a multi-targeted kinase inhibitor which inhibits receptor tyrosine kinases and Src kinases ; has IC 50 s of 2, 7, 2, 16, 13, 5, 0.5, 6, 0.1, 0.4, 1, 0.2 for VEGFR1, VEGFR2, FGFR1 , FGFR2 , PDGFRβ , Fgr, Fyn, Hck, Lck, Lyn, Src , Yes, respectively.

In Vitro

TG 100801 is a topically administered prodrug delivered as an eye drop that is readily converted to the active TG 100572 in the eye.TG 100572 is shown to inhibit hRMVEC cell proliferation, with an IC 50 of 610±72 nM. TG 100801 is formed by derivitization of a phenolic moiety in TG100572 to yield an ester. It displays excellent balance of stability (physical and chemical) with hydrolysis rate. On its own, TG 100801 does not display meaningful anti-kinase activity, as the ester group blocks key interactions with kinase active sites, however exposure to esterases (abundant in mammalian tissues) rapidly liberates active TG100572.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 (ED 50 =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. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

TG 100801 exhibits excellent ocular pharmacokinetics and poor systemic circulation and shows good efficacy in the laser induced choroidal neovascularization model. A concentration of 23.4 µM (C max ) of TG 100572 is reached in 30 min (T max )=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 . TG 100801 nor TG100572 are detectable in plasma following topical delivery of TG 100801, and adverse safety signals (such as weight loss) are not observed even with prolonged dosing schedules. Topical TG 100801 significantly suppresses laser-induced choroidal neovascularlization in mice, and reduces fluorescein leakage from the vasculature and retinal thickening measured by optical coherence tomography in a rat model or retinal vein occlusion.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. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal administration

Rats: Long Evans rats are dosed topically in both eyes with 10 µL of TG 100801 (as a 0.3, 0.6 or 1% solution) or vehicle. A total of 5 topical applications are delivered per eye over a three day period: dosing is performed one hour prior to and six hours after laser-induced thrombosis on Day 1, twice on Day 2, and once the morning of Day 3. One hour after the final topical application, retinal edema is assessed by one of two means . aladdin has not independently confirmed the accuracy of these methods. They are for reference only.

Form:Solid

IC50& Target:VEGFR1 2 nM (IC 50 ) VEGFR2 7 nM (IC 50 ) FGFR1 2 nM (IC 50 ) FGFR2 16 nM (IC 50 ) PDGFRβ 13 nM (IC 50 )