[ 鐧诲綍] [ 鍏嶈垂娉ㄥ唽]
璇曞墏浠櫒缃? title=
浣嶇疆锛欬a href="/">棣栭〉> 浜у搧搴掽/a> > PF-8380
绔嬪嵆鍜ㄨ
鍜ㄨ绫诲瀷锛欬/div>
*濮撳悕锛欬/div>
*鐢佃瘽锛欬/div>
*鍗曚綅锛欬/div>
Email锛欬/div>
*鐣欒█鍐呭锛欬/div>
璇疯缁嗚鏄庢偍鐨勯渶姹傘€
*楠岃瘉鐮侊細
PF-8380
鏈骇鍝佷笉鍚戜釜浜洪攢鍞紝浠呯敤浣滅瀛︾爺绌讹紝涓嶇敤浜庝换浣曚汉浣撳疄楠屽強闈炵鐮旀€ц川鐨勫姩鐗╁疄楠屻€侟/div>
PF-8380鍥剧墖
CAS NO: 1144035-53-9
瑙勬牸: 98%
鍒嗗瓙閲廁 478.33
鍖呰涓庝环鏍硷細
鍖呰 浠锋牸(鍏?
5mg 鐢佃
10mg 鐢佃
50mg 鐢佃
100mg 鐢佃

浜у搧浠嬬粛
Autotaxin inhibitor,potent and specific
CAS锛?144035-53-9
鍒嗗瓙寮忥細C22H21Cl2N3O5
鍒嗗瓙閲忥細478.33
绾害锛?8%
瀛樺偍锛歋tore at -20掳C

Background:

PF-8380 is a potent autotaxin inhibitor with an IC50 of 2.8 nM in isolated enzyme assay and 101 nM in human whole blood.


PF-8380 also inhibits rat autotaxin with an IC50 of 1.16 nM with FS-3 substrate. Potency of PF-8380 is maintained when using enzyme produced from fetal fibroblasts used in combination with lysophosphatidyl choline (LPC) as a substrate. In human whole blood incubated with PF-8380 for 2 h, autotaxin is inhibited with an IC50 of 101 nM[1]. Autotaxin (ATX), an enzyme with lysophospholipase D (lysoPLD) activity, catalyzes the production of lysophosphatidic acid (LPA) from lysophosphatidylcholine (LPC). Pre-treatment of GL261 and U87-MG cells with 1 渭M PF-8380 followed by 4 Gy irradiation results in decreased clonogenic survival, decreases migration (33% in GL261; P=0.002 and 17.9% in U87-MG; P=0.012), decreases invasion (35.6% in GL261; P=0.0037 and 31.8% in U87-MG; P=0.002), and attenuates radiation-induced Akt phosphorylation[2].


The pharmacokinetic profile of PF-8380 is evaluated at an intravenous dose of 1 mg/kg and oral doses of 1 to 100 mg/kg out to 24 h. PF-8380 has mean clearance of 31 mL/min/kg, volume of distribution at steady state of 3.2 L/kg, and effective t1/2 of 1.2 h. Oral bioavailability is moderate, ranging from 43 to 83%. Plasma concentrations increased with single oral escalating doses, but Cmax increased at a rate that is approximately proportional to dose from 1 to 10 mg/kg and less than proportional to dose from 10 to 100 mg/kg. PF-8380 exposures estimated by area under the curve are approximately proportional to dose and linear up to 100 mg/kg. Plasma C16:0, C18:0, and C20:0 LPA levels are measured immediately after collection. Maximal reduction of LPA levels is observed by the 3 mg/kg dose at 0.5 h with all LPA returning at or above baseline at 24 h[1]. Treatment with 10 mg/kg PF-8380 increases tumor-associated vascularity modestly by 20% (P=0.497). When compared to control, treatment of PF-8380 45 min before 4 Gy irradiation decreases vascularity by nearly 48% when compared to control (P=0.031) and by 65% when compared to mice that received radiation alone (P=0.011)[2].


鍙傝€冩枃鐚?
[1]. Gierse J, et al. A novel autotaxin inhibitor reduces lysophosphatidic acid levels in plasma and the site of inflammation. J Pharmacol Exp Ther. 2010 Jul;334(1):310-7.
[2]. Bhave SR, et al. Autotaxin Inhibition with PF-8380 Enhances the Radiosensitivity of Human and Murine Glioblastoma Cell Lines. Front Oncol. 2013 Sep 17;3:236.
[3]. Cao P, et al. Autocrine lysophosphatidic acid signaling activates 尾-catenin and promotes lung allograft fibrosis. J Clin Invest. 2017 Apr 3;127(4):1517-1530.


Baidu
map