TG-100572-Hydrochloride - Src 抑制剂 - 生命科学试剂 - MedChemExpress

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作靶点: Src; VEGFR; FGFR; PDGFR作通路: Protein Tyrosine Kinase/RTK储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO :

2、44 mg/mL (85.87 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液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，并请注意储备液的保存式和期限。BIOLOGICAL ACTIVITY物活性 TG 100572 Hydrochloride是

3、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，PDGFR，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 nM。IC50 & Target VEGFR1 VEGFR2 FGFR1 FGFR22 nM (IC50) 7 nM (IC50) 2 nM (IC50) 16 nM (IC50)1/3 Master of Small Molecules 您边的抑制剂

4、师www.MedChemEPDGFR13 nM (IC50)体外研究 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.体内研究 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.户使本产品发表的科研献 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 您边的抑制剂师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