Erdafitinib-JNJ-42756493-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEErdafitinibCat. No.: HY-18708CAS No.: 1346242-81-6Synonyms: JNJ-42756493分式: CHNO分量: 446.54作靶點(diǎn): FGFR作通路: Protein Tyrosine Kinase/RTK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 : 33 mg/mL (

2、73.90 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 2.2394 mL 11.1972 mL 22.3944 mL5 mM 0.4479 mL 2.2394 mL 4.4789 mL10 mM 0.2239 mL 1.1197 mL 2.2394 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?，配制前?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

3、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: 2.08 mg/mL (4.66 mM); Clear solution2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.08 mg/mL (4.66 mM); Clear solution1/2 Master of Small Molecule

4、s 您邊的抑制劑師www.MedChemE3. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.08 mg/mL (4.66 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Erdafitinib (JNJ-42756493)有效的有服活性的 FGFR 家族抑制劑；抑制FGFR1-4活性的 IC50 分別為1.2,2.5, 3.0和5.7 nM。IC50 & Target IC50: 1.2 nM (FGFR1), 2.5 nM (FGFR2), 3.0 nM (FGFR3)and 5.7 nM (FGFR4) 1

5、體外研究 Erdafitinib inhibits the tyrosine kinase activities of FGFR1-4 in time-resolved fluorescence assays with IC50values of 1.2, 2.5, 3.0 and 5.7 nM, respectively. The closely related VEGFR2 kinase is less potently inhibited(30-fold less potent compared to FGFR1) by erdafitinib, with an IC50 value o

6、f 36.8 nM. JNJ-42756493 bindsFGFR1, 3, 4, and 2 with Kd values of 0.24, 1.1, 1.4 and 2.2 nM, respectively. The Kd value for VEGFR2 ishigher at 6.6 nM. JNJ-42756493 inhibits proliferation of FGFR1, 3, and 4 expressing cells with IC50 values of22.1, 13.2, and 25nM, respectively 1.體內(nèi)研究 In xenografts fr

7、om human tumor cell lines or patient-derived tumor tissue with activating FGFR alterations,Erdafitinib administration results in potent and dose-dependent antitumor activity accompanied bypharmacodynamic modulation of phospho-FGFR and phospho-ERK in tumors 1.PROTOCOLCell Assay 1 Erdafitinib is disso

8、lved in DMSO. KATO III, RT-112, A-204, RT-4, DMS-114, A-427 and MDA-MB-453 cellsare treated with erdafitinib (from 10 M to 0.01 nM in 2% DMSO, final concentration). Following 4-dayincubation, cell viability is determined using MTT reagent. The optical density is determined at 540 nm 1.MCE has not in

9、dependently confirmed the accuracy of these methods. They are for reference only.Animal Mice: Mice bearing SNU-16 human gastric carcinoma (FGFR2 amplified) xenograft tumors are dosed orallyAdministration 1 with 0, 3, 10 or 30mg/kg JNJ-42756493. Tumor tissue and mouse plasma (3 mice per time point) a

10、reharvested at 0.5, 1, 3, 7, 16 and 24h post-dosing 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Perera TP, et al. Discovery and pharmacological characterization of JNJ-42756493 (erdafitinib), a functionally selective small moleculeFGFR family inhibitor. Mol Cancer Ther. 2017 Mar 24. pii: molcanther.0589.2016.McePdfHeightCaution: Product has not been fully