AMG-487 - CXCR3 Antagonist - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEAMG 487Cat. No.: HY-15319CAS No.: 473719-41-4分式: CHFNO分量: 603.59作靶點(diǎn): CXCR作通路: GPCR/G Protein; Immunology/Inflammation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 : 41 mg/mL (67.93 mM)* mea

2、ns soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 1.6568 mL 8.2838 mL 16.5675 mL5 mM 0.3314 mL 1.6568 mL 3.3135 mL10 mM 0.1657 mL 0.8284 mL 1.6568 mL請根據(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，并請注意儲(chǔ)備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 AMG 487種有效的、具有服活性的、選擇性的趨化因受體3 (CXCR3) 拮抗劑，抑制 CXC

3、L10和CXCL11與 CXCR3 結(jié)合的 IC50 值分別為 8.0 和 8.2 nM。IC50 & Target 125I-IP10-CXCR3 125I-ITAC-CXCR38 nM (IC50) 8.2 nM (IC50)1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE體外研究 AMG 487 inhibits CXCR3-mediated cell migration by the three CXCR3 chemokines (IP-10 IC50=8 nM, ITACIC50=15 nM, and MIG IC50=36 nM).

4、 Furthermore, AMG 487 inhibits calcium mobilization in response toITAC (IC50=5 nM) 1. AMG487 (1 M) develops into fewer lung metastases, and the lungs are significantlysmaller than vehicle-treated lungs 2. AMG487 abrogates proliferation/survival of C26 tumour cells 3.體內(nèi)研究 AMG 487 (0.03-10 mg/kg, s.c.

5、) exhibits significant reduction in cellular infiltration into the lungs in a dosedependent manner 1. AMG487 (5 mg/kg, s.c., twice daily) develops fewer metastases than that in vehicle-treated mice 2. AMG487 (5 mg/kg, s.c.)-treated mice exhibits fewer pulmonary nodules than the controlmice in both t

6、he models. AMG487 reduces the tumour volume 3.PROTOCOLKinase Assay 3 Cells are then lysed and sonicated in 50 mM Hepes pH 7.5, 150 mM NaCl, 20 mM EDTA, 1 mM PMSF, 10 g/mL leupeptin, 2 g/mL aprotinin and 0.2% NP-40. Equal amount of lysates are mixed in substrate buffer(50 mM Hepes, 100 mM NaCl, 1 mM

7、EDTA, 10% sucrose, 0.5% CHAPS, 5 mM dithiothreitol) with Ac-DEVD-AMC substrate and caspase-3/7 substrate in a microtiter plate. Production of fluorigenic substrate ismeasured continuously at 37C in a spectrophotometer Ascent Fluoroskan and the caspase activity(expressed as U/mg of protein) is define

8、d as the amount of enzyme cleaving 1 nmol of substrate/min.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 3 Colon cancer cells are seeded at a density of 104 cells cm2 and incubated either in serum-enriched mediumor in base medium (containin

9、g 0.1% bovine serum albumin, BSA) supplemented or not with variousconcentrations of rCXCL9, rCXCL10 and rCXCL11 for the indicated periods of time before being eithertrypsin-detached, collected and enumerated or re-fed with fresh medium for 3 days, harvested andenumerated. The morphology of the CRC c

10、ells is observed through an inverted optical microscope at 20magnification, and photographs are taken at day 7.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Local tumor growth and spontaneous metastasis are evaluated by injecting 3105 viable tu

11、mor cells s.c.Administration 2 proximal to the right abdominal mammary gland of syngeneic female mice. Tumor diameters are measuredby caliper twice weekly, and mice are euthanized on an individual basis when the s.c. tumor measured 18mm in diameter or earlier if the mouse seemed moribund. The lungs

12、are removed and weighed, and surfacetumor colonies are quantified in a blinded fashion under a dissecting microscope. Experimental metastasis isevaluated by injecting 9104 viable tumor cells i.v. into the lateral tail vein of syngeneic female mice. All miceare euthanized on day 21 posttransplantatio

13、n or earlier if the mice seemed moribund. The lungs are removedand weighed, and surface tumor colonies are quantified in a blinded fashion under a dissecting microscope.A 50% hydroxypropyl-cyclodextrin solution is prepared; at 20%, this solution serves as the vehicle.AMG487 is added to the 50% solut

14、ion, and it is incubated in a sonicating water bath for 2 hours withoccasional vortexing. Distilled water is added to give the appropriate final concentration of AMG487 in 20% ofhydroxypropyl-cyclodextrin.MCE has not independently confirmed the accuracy of these methods. They are for reference only.

15、2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Exp Cell Res. 2018 Oct 1;371(1):162-174. PLoS One. 2015 Mar 23;10(3):e0121140. Neurosci Lett. 2018 Nov 15. pii: S0304-3940(18)30808-5.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Johnson M, et al. Discovery and opt

16、imization of a series of quinazolinone-derived antagonists of CXCR3. Bioorg Med Chem Lett. 2007Jun 15;17(12):3339-43.2. Walser TC, et al. Antagonism of CXCR3 inhibits lung metastasis in a murine model of metastatic breast cancer. Cancer Res. 2006 Aug1;66(15):7701-7.3. Cambien B, et al. Organ-specifi

17、c inhibition of metastatic colon carcinoma by CXCR3 antagonism. Br J Cancer. 2009 Jun2;100(11):1755-64.4. Henne KR, et al. Sequential metabolism of AMG 487, a novel CXCR3 antagonist, results in formation of quinone reactive metabolitesthat covalently modify CYP3A4 Cys239 and cause time-dependent inhibit