ACHP-Hydrochloride-IKK-2-Inhibitor-VIII-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEACHP HydrochlorideCat. No.: HY-13060CAS No.: 406209-26-5Synonyms: IKK-2 Inhibitor VIII分式: CHClNO分量: 400.9作靶点: IKK作通路: NF-B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 : 50 mg/mL (124.72 mM

2、; Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.4944 mL 12.4719 mL 24.9439 mL5 mM 0.4989 mL 2.4944 mL 4.9888 mL10 mM 0.2494 mL 1.2472 mL 2.4944 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，配制前请先配制澄清的储备液，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；澄清的储备液

3、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)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (6.24 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 (6.24 mM); Clear solution1/3 Master of Small Molecules 您边的抑制剂师www.MedChemEBIOLOGICAL

4、ACTIVITY物活性 ACHP Hydrochloride种有效，选择性的 IKK- 抑制剂, IC50 为 8.5 nM。IC50 & Target IKK- IKK-8.5 nM (IC50) 250 nM (IC50)体外研究 ACHP (Compound 4j) exhibits potent IKK- inhibitory (IC50: 8.5 nM) and cellular activities (IC50=40 nM, inA549 cells). ACHP moderately inhibits IKK- with an IC50 of 250 nM but exhibit

5、s good selectivity towardsother kinases, such as IKK3, Syk and MKK4 (IC5020,000 nM). Moreover, ACHP demonstrates quite potentactivity in various cellular assays. ACHP inhibits NF-B-dependent reporter gene activation in TNF-activatedHEK293 cells and PMA/calcium ionophore-activated Jurkat T cells. ACH

6、P fails to inhibit PMA-induced AP-1activation in MRC-5 cells and PMA/calcium ionophore induced NF-B dependent reporter gene transcriptionin Jurkat cells even at concentrations exceeding 10 M. ACHP selectively interferes with the NF-B signalingcascade by inhibition of IKK- in living cells 1. ACHP inh

7、ibits the growth of these cells in a dose-dependentmanner. Tax-active cell lines are more susceptible to ACHP than Tax-inactive cell lines and Jurkat (IC50values in Tax-active cell lines, Tax-inactive cell lines or Jurkat are 3.11.3M, 10.71.7M and 23.6M,respectively), suggesting that the growth of T

8、ax-active cells depends on NF-B more than Tax-inactive cells2.体内研究 ACHP (Compound 4j) is orally bioavailable in mice and rats and demonstrates significant in vivo activity inanti-inflammatory models (arachidonic acid-induced mouse ear edema model). ACHP has reasonableaqueous solubility (0.12 mg/mL i

9、n pH 7.4 isotonic buffer) and excellent Caco-2 permeability (Papp 62.310-7cm/s), and demonstrates orally bioavailability in mice (BA: 16%) and rats (BA: 60%). The favourablebioavailability of ACHP in rats is likely due to its low clearance (0.33 L/h/kg). In an acute inflammation model,ACHP exhibits

10、oral efficacy at 1 mg/kg in a dose-dependent manner 1.PROTOCOLCell Assay 2 HTLV-1-infected T-cell lines, ATL-35T, 81-66/45, MJ, and MT-2 cells, human ATL cell lines established fromATL patients, ATL-102, ED-40515() and TL-Om1 cells, and a HTLV-1-negative T-cell leukemia cell lineJurkat are used in t

11、his study. Approximately 1.5104 cells are cultured in 96-well plate in triplicates at 37C.Growth inhibitory effect of ACHP (0.01, 0.1, 1, 5, 10, 50 and 100 M) is determined using MTT assay. Opticaldensities (OD) at 570 and 630nm are measured with multiplate reader. Cell viability (%) is calculated 2

12、.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 1Administration 1 In vivo arachidonic acid-induced ear edema in mice: ear edema is induced by topical application ofarachidonic acid (500 g/ear). ACHP (0.3, 1 and 3 mg/kg, p.o.), Dexamethasone

13、 and vehicle (10%cremophor in saline) are given po 60 min before the arachidonic acid application. Ear thickness is measuredat 0, 1, 3 and 6 h after the arachidonic acid application.MCE has not independently confirmed the accuracy of these methods. They are for reference only.2/3 Master of Small Mol

14、ecules 您边的抑制剂师www.MedChemE户使本产品发表的科研献 J Bone Miner Res. 2019 May 20. Harvard Medical School LINCS LIBRARYSee more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Murata T, et al. Synthesis and structure-activity relationships of novel IKK-beta inhibitors. Part 3: Orally active anti-inflammatory agents.Bioorg Med Chem Lett. 2004 Aug 2;14(15):4019-22.2. Sanda T, et al. Induction of cell death in adult T-cell leukemia cells by a novel IkappaB kinase inhibitor. Leukemia. 200