(±)-AMG 487 |
カタログ番号GC15045 |
CXCR3拮抗剤
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 473719-41-4
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
ここでは、(±)-AMG 487の代わりにAMG 487が説明されています。 AMG 487は、化学療法薬(C-X-Cモチーフ)受容体3(CXCR3)の強力で選択的な拮抗剤です[1]。 AMG 487は、IC50値がそれぞれ8、15、36 nMである3つのCXCR3ケモカインIP-10、ITACおよびMIGによって誘発されたCXCR3介在細胞移動を阻害しました[2]。
CXCR3は、化学療法受容体であり、Th1フェノタイプを持つ活性化したCD4陽性およびCD8陽性T細胞に主に発現しています。また、B細胞、悪性T細胞、自然殺傷細胞(NK細胞)、星形グリアも発現します。そのリガンドはMig(CXCL9)、IP-10(CXCL10)およびITAC(CXCL11)です。これらのリガンドは主にIFN-γによって誘導されます。 CXCR3とそのリガンドは、炎症性腸疾患、関節リウマチ、乾癬、多発性硬化症および移植拒絶反応などの多くの炎症性疾患に関与していることが示唆されています[2]。
AMG487は、CXCL9、CXCL10、またはCXCL11によって仲介されるin vitroリンパ球の移動を阻害しました。 AMG487は、正常または無血清増殖条件下で24時間、48時間、72時間後の66.1腫瘍細胞の増殖に影響を与えませんでした。ただし、それは腫瘍細胞がCXCL9への移行を70%抑制しました[3]。
マウスの肺では、気管切開後にブレオマイシンを気道内投与することで、肺への細胞浸潤が誘発されました。最低用量以外のAMG 487処理群はすべて、肺への細胞浸潤が有意に減少しました(Student's t-testによるp <0.005)。皮下投与された3 mg / kg AMG 487を1日2回投与した場合、CXCR3欠損マウスと同等の移動抑制効果が得られました(グループあたり8〜12匹)[2]。高度な悪性腫瘍細胞株66.1をAMG 487で前処理し、免疫能力のある雌マウスにi.v.注射しました。AMG487は実験的な肺転移に対して抑制効果を示しました[3]。
References:
[1]. Tonn GR, Wong SG, Wong SC, et al. An inhibitory metabolite leads to dose- and time-dependent pharmacokinetics of (R)-N-{1-[3-(4-ethoxy-phenyl) -4-oxo-3,4-
dihydro-pyrido[2,3-d]pyrimidin-2-yl]-ethyl}-N-pyridin-3-yl-methyl-2-(4-trifluoromethoxy-phenyl)-acetamide (AMG 487) in human subjects after multiple dosing. Drug Metabolism and Disposition, 2009, 37(3): 502-513.
[2]. Johnson M, Li AR, Liu J, et al. Discovery and optimization of a series of quinazolinone-derived antagonists of CXCR3. Bioorganic & medicinal chemistry letters, 2007, 17(12): 3339-3343.
[3]. Walser TC, Rifat S, Ma X, et al. Antagonism of CXCR3 inhibits lung metastasis in a murine model of metastatic breast cancer. Cancer research, 2006, 66(15): 7701-7707.
Cas No. | 473719-41-4 | SDF | |
Chemical Name | N-(1-(3-(4-ethoxyphenyl)-4-oxo-3,4-dihydropyrido[2,3-d]pyrimidin-2-yl)ethyl)-N-(pyridin-3-ylmethyl)-2-(4-(trifluoromethoxy)phenyl)acetamide | ||
Canonical SMILES | CCOC1=CC=C(N2C(C(N(C(CC3=CC=C(OC(F)(F)F)C=C3)=O)CC4=CN=CC=C4)C)=NC5=C(C2=O)C=CC=N5)C=C1 | ||
Formula | C32H28F3N5O4 | M.Wt | 603.59 |
溶解度 | <60.36mg/ml in DMSO | Storage | Store at -20°C |
General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. |
Prepare stock solution | |||
1 mg | 5 mg | 10 mg | |
1 mM | 1.6568 mL | 8.2838 mL | 16.5675 mL |
5 mM | 0.3314 mL | 1.6568 mL | 3.3135 mL |
10 mM | 0.1657 mL | 0.8284 mL | 1.6568 mL |
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