ACHP-Hydrochloride-IKK-2-Inhibitor-VIII-DataSheet-生命科學(xué)試劑-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作靶點(diǎn): IKK作通路: NF-B儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 50 mg/mL (124.72 mM

2、; Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液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請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存式和期限。體內(nèi)實(shí)驗(yàn) 請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍福渲魄罢?qǐng)先配制澄清的儲(chǔ)備液，再依次添加助溶劑(為保證實(shí)驗(yàn)結(jié)果的可靠性，體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使；澄清的儲(chǔ)備液

3、可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (6.24 mM); Clear solution2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (6.24 mM); Clear solution1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEBIOLOGICAL

4、ACTIVITY物活性 ACHP Hydrochloride種有效，選擇性的 IKK- 抑制劑, IC50 為 8.5 nM。IC50 & Target IKK- IKK-8.5 nM (IC50) 250 nM (IC50)體外研究 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.體內(nèi)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 您邊的抑制劑師www.MedChemE戶使本產(chǎn)品發(fā)表的科研獻(xiàn) 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