1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemETG 100572 HydrochlorideCat. No.: HY-10185CAS No.: 867331-64-4分式: CHClNO分量: 512.43作靶點: Src; VEGFR; FGFR; PDGFR作通路: Protein Tyrosine Kinase/RTK儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數據體外實驗 DMSO :

2、44 mg/mL (85.87 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 1.9515 mL 9.7574 mL 19.5149 mL5 mM 0.3903 mL 1.9515 mL 3.9030 mL10 mM 0.1951 mL 0.9757 mL 1.9515 mL請根據產品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 TG 100572 Hydrochloride是

3、多靶點激酶抑制劑，抑制受體酪氨酸激酶 (receptor tyrosine kinases) 和Src激酶 (Src kinases); 對VEGFR1，VEGFR2，FGFR1，FGFR2，PDGFR，Fgr，Fyn，Hck，Lck，Lyn，Src，Yes 的IC50 值分別為2，7，2，16，13，5，0.5，6，0.1，0.4，1，0.2 nM。IC50 & Target VEGFR1 VEGFR2 FGFR1 FGFR22 nM (IC50) 7 nM (IC50) 2 nM (IC50) 16 nM (IC50)1/3 Master of Small Molecules 您邊的抑制劑

4、師www.MedChemEPDGFR13 nM (IC50)體外研究 TG 100572 shows sub-nanomolar activity against the Src family as well as RTK such as VEGFR1 and R2,FGFR1 and R2, and PDGFR. TG 100572 inhibits vascular endothelial cell proliferation (ED50=61071 nM)and blocks VEGF-induced phosphorylation of extracellular signal-reg

5、ulated kinase. TG 100572 inducesapoptosis in rapidly proliferating, but not quiescent, endothelial cell cultures 1. TG 100572 is shown to inhibithRMVEC cell proliferation, with an IC50 of 61072 nM. This suggests that TG 100572 has the therapeuticpotential to inhibit VEGF function in ocular endotheli

6、al cells, a contributing factor to pathological angiogenesisin diseases such as AMD and PDR 2.體內研究 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 toxi

7、city 1.A concentration of 23.4 M (Cmax) of TG 100572 is reached in 30 min (Tmax)=0.5 h) in the choroid and thesclera. However, the levels of TG 100572 in the retina are relatively low. The half-life of TG 100572 in oculartissues is very short; hence, the compound is administered topically minimum t.

8、i.d. to maintain appropriatedrug levels in the eye. The maximum concentration one can achieve in formulations using TG 100572 is0.7% w/v 2.PROTOCOLCell Assay 1 For proliferation assays, human retinal microvascular EC plated in 96-well cluster plates are cultured for 48hr in the presence of either TG

9、 100572 (2 nM-5 M) or DMSO; medium contained 10% FBS, 50 g/mLheparin, and 50 ng/mL rhVEGF. Cell numbers are then assessed using an XTT-based assay 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice: C57BL/6 mice (15-20 g) are dosed i.p. twice

10、 daily for 4 days with 5 mg/ kg TG 100572, followed by aAdministration 1 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) bydelivering a single 1

11、0 L drop to both eyes for a total of two days, and both plasma and eyes harvested priorto or 0.5, 1, 3, 5, or 7 hr after the Day 2 dosing 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產品發表的科研獻 Science. 2017 Dec 1;358(6367). Am J Pathol. 2019 Jul

12、24. pii: S0002-9440(19)30624-8.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Doukas J, et al. Topical administration of a multi-targeted kinase inhibitor suppresses choroidal neovascularization and retinal edema. J2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemECell Physiol.

13、 2008 Jul;216(1):29-37.2. Palanki MS, et al. Development of prodrug 4-chloro-3-(5-methyl-3-4-(2-pyrrolidin-1-ylethoxy)phenylamino-1,2,4-benzotriazin-7-yl)phenyl benzoate (TG100801): a topically administered therapeutic candidate in clinical trials for the treatment of age-related maculardegeneration. J Med Chem. 2008 Mar 27;51(6):1546-59.McePd