TG 100801 (Hydrochloride)
TG 100801 (Hydrochloride) Basic information
- Product Name:
- TG 100801 (Hydrochloride)
- Synonyms:
-
- TG 100801 (Hydrochloride)
- TG 100801 HCl
- TG100801 HYDROCHLORIDE;TG-100801 HYDROCHLORIDE
- 4-Chloro-3-(5-methyl-3-((4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)amino)benzo[E][1,2,4]triazin-7-yl)phenyl benzoate hydrochloride
- CAS:
- 1018069-81-2
- MF:
- C33H31Cl2N5O3
- MW:
- 616.54
- Mol File:
- 1018069-81-2.mol
TG 100801 (Hydrochloride) Chemical Properties
- storage temp.
- Store at -20°C
- solubility
- DMSO : 5 mg/mL (8.11 mM; Need ultrasonic)
- form
- Powder
TG 100801 (Hydrochloride) Usage And Synthesis
Uses
TG 100801 Hydrochloride 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 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.
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 (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[1]. 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[2].
IC 50
VEGFR1: 2 nM (IC50); VEGFR2: 7 nM (IC50); FGFR1: 2 nM (IC50); FGFR2: 16 nM (IC50); PDGFRβ: 13 nM (IC50)
References
[1] Palanki MS, et al. Development of prodrug 4-chloro-3-(5-methyl-3-{[4-(2-pyrrolidin-1-ylethoxy)phenyl]amino}-1,2,4-benzotriazin-7-yl)phenyl benzoate (TG100801): a topically administered therapeutic candidate in clinical trials for the treatment of age-related macular degeneration. J Med Chem. 2008 Mar 27;51(6):1546-59. DOI:10.1021/jm7011276
[2] Doukas, John, et al. Topical administration of a multi-targeted kinase inhibitor suppresses choroidal neovascularization and retinal edema. Journal of Cellular Physiology (2008), 216(1), 29-37.
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