雷馬曲班由德國拜耳公司研制，是作為抗心血管疾病藥物開發(fā)的TP抑制劑，與日本新藥株式會社合作在日本推廣上市。僅在日本被批準(zhǔn)為治療哮喘和過敏性鼻炎的藥物。
Ramatroban 是一種選擇性血栓素 A2 (TxA2，IC50=14 nM) 拮抗劑。Ramatroban 還通過抑制 PGD2 結(jié)合從而拮抗 CRTH2 (IC50=113 nM)。
| Target | Value |
TxA2 receptor
()
|
Ramatroban is a potent human thromboxane receptor (hTP) antagonist with an IC
50
of 18 nM in a human TP binding assay. Ramatroban inhibits prostaglandin D
2
receptor DP2 (CRTH2) with an IC
50
of 113 nM in a human DP2 binding assay. Ramatroban also inhibits human CYP isoform CYP2C9 with an IC
50
of 15 μM. Ramatroban is a selective thromboxane-type prostanoid (TP) receptor antagonist. PGD
2
-stimulated human eosinophil migration is shown to be mediated exclusively through activation of CRTH2, and surprisingly, these effects are completely inhibited by Ramatroban. Ramatroban is an antagonist for CRTH2, and inhibits PGD
2
-induced migration of eosinophils via CRTH2 blockade.
3
H-labeled PGD
2
binds to a single site on CRTH2 transfectants with high affinity (K
D
=6.3 nM, B
max
=450 pM). Nonlabeled PGD
2
inhibits the binding of
3
H-labeled PGD
2
to CRTH2 transfectants in a concentration-dependent manner with an EC
50
value of 2.7 nM. Ramatroban shows significant inhibitory effects on the binding of
3
H-labeled PGD
2
to CRTH2, albeit with much lower potency (IC
50
=100 nM). Ramatroban also inhibits PGD
2
-induced Ca
2+
mobilization in CRTH2 transfectants to almost the same extent with an IC
50
value of 30 nM. Ramatroban completely inhibits the PGD
2
-induced migration of eosinophils in a concentration-dependent manner with an IC
50
value of 170 nM.
Ramatroban is an orally bioavailable small molecule antagonist of CRTH2. Systemic administration of Ramatroban (30 mg/kg) in CRTH2
+/+
mice produces the same effects as seen in CRTH2 deficiency. Ramatroban completely blocks LPS-induced decreases in social and object exploratory behavior (p<0.01). In addition, tumor-impaired social interaction and object exploratory behavior in CRTH2
+/+
mice are completely reversed by a single injection of Ramatroban, even when the tumor is enlarged.
用途
雷馬曲班為高效的選擇性TxA2/PGH2受體拮抗劑，可與平滑肌和血小板的TxA2受體特異性結(jié)合。雷馬曲班的抗過敏反應(yīng)基于抑制血管通透性和鼻粘膜高敏性及防止其它炎性反應(yīng)發(fā)生。用于過敏性鼻炎。
