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TG 100801
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
TG 100801图片
CAS NO:867331-82-6
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
200mg电议

产品介绍
TG 100801 是TG 100572的前药,通过去酯化产生TG 100572,开可用于黄斑变性的研究。TG 100572 是多靶点激酶抑制剂,抑制受体酪氨酸激酶 (receptor tyrosine kinases) 和Src激酶 (Src kinases); 对VEGFR1,VEGFR2,FGFR1,FGFR2,PDGFRβ,Fgr,Fyn,Hck,Lck,Lyn,Src,Yes 的IC50值分别为2,7,2,16,13,5,0.5,6,0.1,0.4,1,0.2。
生物活性

TG 100801 is a prodrug that generates TG 100572 by de-esterification in development to treat age-related macular degeneration. TG 100572 is a multi-targeted kinase inhibitor which inhibitsreceptor tyrosine kinasesandSrckinases; hasIC50s 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.

IC50& Target

VEGFR1

2 nM (IC50)

VEGFR2

7 nM (IC50)

FGFR1

2 nM (IC50)

FGFR2

16 nM (IC50)

PDGFRβ

13 nM (IC50)

体外研究
(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 IC50of 610±72 nM[1]. 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 (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[2].

体内研究
(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].

Clinical Trial
分子量

580.08

性状

Solid

Formula

C33H30ClN5O3

CAS 号

867331-82-6

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式
Powder-20°C3 years
4°C2 years
In solvent-80°C6 months
-20°C1 month
溶解性数据
In Vitro: 

DMSO : 5.56 mg/mL(9.58 mM;Need ultrasonic)

配制储备液
浓度溶剂体积质量1 mg5 mg10 mg
1 mM1.7239 mL8.6195 mL17.2390 mL
5 mM0.3448 mL1.7239 mL3.4478 mL
10 mM---------
*

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效
储备液的保存方式和期限:-80℃, 6 months; -20℃, 1 month。-80℃ 储存时,请在 6 个月内使用,-20℃ 储存时,请在 1 个月内使用。