1644670-37-0
1644670-37-0 結(jié)構(gòu)式
基本信息
EOS-62416
4-((2S,4S)-4-ethoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoicacid
Benzoic acid, 4-[(2S,4S)-4-ethoxy-1-[(5-methoxy-7-methyl-1H-indol-4-yl)methyl]-2-piperidinyl]-
物理化學性質(zhì)
常見問題列表
伊普可泮的作用機制為特異性結(jié)合因子B，抑制C3轉(zhuǎn)化酶前體（C3bB）的形成，從而阻斷補體級聯(lián)反應的放大，最終減少膜攻擊復合物（MAC）的生成及細胞溶解。該藥是全球首個口服補體因子B抑制劑，目前獲批用于治療陣發(fā)性夜間血紅蛋白尿（PNH）——一種罕見的補體介導的慢性血液疾病，此前治療依賴靜脈注射抗C5抗體（如依庫珠單抗）。
KD: 7.9 nM (factor B)
IC50: 10 nM (factor B)
Iptacopan (LNP023) demonstrates potent inhibition of alternative complement pathway (AP)-induced membrane attack complex (MAC) formation in 50% human serum (IC
50
value of 130 nM).
Iptacopan (LNP023) exhibits excellent selectivity over other proteases affording IC
50
values of >30 μM across a panel of 41 human proteases, including the AP protein factor D (>100 μM).
Iptacopan (LNP023; 20-180 mg/kg; oral administration) prevents KRN (150 μL)-induced arthritis in mice and is effective upon prophylactic and therapeutic dosing in an experimental model of membranous nephropathy in rats.
LNP023 exhibits moderate half-lives (T
1/2
; Wistar Han rats 3.4 h, beagle dogs 5.5 h) and C
max
(Wistar Han rats 410 nM, beagle dogs 2200 nM) following oral administration (rat 30 and, dog 10 mg/kg).
Iptacopan exhibits terminal elimination half-lives (T
1/2
; Wistar Han rats 7 h, beagle dogs 5.6 h) due to high plasma clearance (8, and 2 mL/min/kg respectively combined with large volumes of distribution (2.3, and 0.6 L/kg respectively) following intravenous administration (rat 1.0 and, dog 0.1 mg/kg).
| Animal Model: | C57BL/6 mice with KRN-induced arthritis |
| Dosage: | 20, 60, and 180 mg/kg |
| Administration: | Orally gavaged; twice a day (b.i.d.) for 14 days |
| Result: | Blocked KRN-induced arthritis. |