LYN-1604-hydrochloride - ULK1 Activator - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemELYN-1604 hydrochlorideCat. No.: HY-101923A分式: CHClNO分量: 621.08作靶点: ULK作通路: Autophagy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 : 100 mg/mL (161.01 mM; Need ultrasonic)Mass Solvent1 mg 5

2、mg 10 mg Concentration制备储备液1 mM 1.6101 mL 8.0505 mL 16.1010 mL5 mM 0.3220 mL 1.6101 mL 3.2202 mL10 mM 0.1610 mL 0.8050 mL 1.6101 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。体内实验 请根据您的实验动物和给药式选择适当的溶解案，配制前请先配制澄的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的作液，建议您现现配，当天使；澄的储备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)

3、：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (4.03 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (4.03 mM); Clear solution3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (4.03 mM); Clear solution1/3 Master of Smal

4、l Molecules 您边的抑制剂师www.MedChemEBIOLOGICAL ACTIVITY物活性 LYN-1604 hydrochloride种有效的 ULK1 激动剂，EC50 值为18.94 nM。IC50 & Target EC50: 18.94 nM (ULK1) 1体外研究 LYN-1604 is found as a potential ULK1 activator with enzymatic activity of 195.7% at 100 nM and IC50 of1.66 M against MDA-MB-231 cells. LYN-1604 display

5、s a good effect on ULK1 activation with an EC50 of18.94 nM. LYS50, LEU53, and TYR89 are key to the activation site of LYN-1604. LYN-1604 induces celldeath in MDA-MB-231 cells. LYN-1604 could modulate ATF3 and RAD21 through ULK1 in MDA-MB-231cells. LYN-1604 can also increase cleavage of caspase3 and

6、induce apoptosis. LYN-1604 induces cell deathinvolved in ATF3, RAD21, and caspase3, accompanied by autophagy and apoptosis 1.体内研究 LYN-1604 could significantly inhibit the growth of xenograft MDA-MB-231 cells. The body weights of mice arestable. LYN-1604 induces remarkable autophagy in vivo. LYN-1604

7、 has good therapeutic potential bytargeting ULK1-modulated cell death of TNBC, thus making a ULK1 agonist that can be utilized as a newdrug for triple negative breast cancer therapy 1.PROTOCOLKinase Assay 1 The ULK1 kinase enzyme, substrate, ATP and compound (include LYN-1604) are diluted in kinase

8、buffer.Then, 1 L of compound or (5% DMSO), 2 L of ULK1 kinase enzyme or purified wild-type and mutant ULK1(K50A, L53A, Y89A) (10 ng), or 2 L of MBP (0.1 g/L)/ATP (10 M) mix are added to the wells of a 384well low volume plate. After incubation at room temperature for 60 minutes, 5 L of kinase assay

9、reagent isadded per well. The plates are incubated at room temperature for 40 minutes and then 10 L of kinasedetection reagent is added. After incubation at room temperature for 30 minutes, the luminescence isrecorded. The EC50 values are calculated using nonlinear regression with normalized dose re

10、sponse fitting1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 1 MCE-7, MDA-MB-231 and MDA-MB-468 cells are treated with LYN-1604, cell viability is measured by theMTT assay 1.MCE has not independently confirmed the accuracy of these methods

11、. They are for reference only.Animal Mice: Mice are injected subcutaneously with MDA-MB-231 cells. When the tumors reach 100 mm3 inAdministration 1 volume, the mice are divided into four groups. Three groups are treated with different doses of LYN-1604once a day by intragastric administration for 14

12、 days (low dose, 25 mg/kg; median dose, 50 mg/kg; highdose, 100 mg/kg), whereas the control group is treated with vehicle control. During the treatment, the tumorvolumes and body weight are measured every day until the end of the study. At the end of treatment, all miceare sacrificed. The spleen, li

13、ver, kidney and tumor tissue are harvested, weighed, and photographed, thenimmediately frozen in liquid nitrogen or fixed in formalin 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemE户使本产品发表的科研献 Biochem J. 2019 Mar 12;476(5):875-887.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Zhang L, et al. Discovery of a small molecule targeting ULK1-modulated cell death of triple negative breast cancer in vitro and in vivo.Chem Sci. 2017 Apr 1;8(4):268