伊普可泮
| 中文名稱 | 伊普可泮 |
|---|---|
| 中文同義詞 | IPTACOPAN;化合物 T11864;4-((2S,4S)-4-乙氧基-1-((5-甲氧基-7-甲基-1H-吲哚-4-基)甲基)哌啶-2-基)苯甲酸;伊帕替康;化合物 IPTACOPAN;伊普塔克泮;化合物IPTACOPAN,10 MM DMSO 溶液;伊普可泮 |
| 英文名稱 | Iptacopan |
| 英文同義詞 | 4-((2S,4S)-4-ethoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoicacid;EOS-62416;LNP023;Benzoic acid, 4-[(2S,4S)-4-ethoxy-1-[(5-methoxy-7-methyl-1H-indol-4-yl)methyl]-2-piperidinyl]-;LNP023(LNP-023;LNP0233;Iptacopan, 10 mM in DMSO;4-((2S,4S)-4-Ethoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid , Iptacopan |
| CAS號(hào) | 1644670-37-0 |
| 分子式 | C25H30N2O4 |
| 分子量 | 422.52 |
| EINECS號(hào) | |
| 相關(guān)類別 | 醫(yī)藥原料 |
| Mol文件 | 1644670-37-0.mol |
| 結(jié)構(gòu)式 |  |
伊普可泮 性質(zhì)
| 沸點(diǎn) | 599.1±50.0 °C(Predicted) |
|---|---|
| 密度 | 1.25±0.1 g/cm3(Predicted) |
| 儲(chǔ)存條件 | Store at -20°C |
| 溶解度 | DMSO：50.0（最大濃度 mg/mL）；118.34（最大濃度 mM） |
| 酸度系數(shù)(pKa) | 4.07±0.10(Predicted) |
| 形態(tài) | 固體 |
| 顏色 | 米白色至灰色 |
| InChIKey | RENRQMCACQEWFC-UGKGYDQZSA-N |
| SMILES | C(O)(=O)C1=CC=C([C@@H]2C[C@@H](OCC)CCN2CC2=C(OC)C=C(C)C3=C2C=CN3)C=C1 |
伊普可泮的作用機(jī)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(bǔ)體級(jí)聯(lián)反應(yīng)的放大，最終減少膜攻擊復(fù)合物（MAC）的生成及細(xì)胞溶解。該藥是全球首個(gè)口服補(bǔ)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(jiàn)的補(bǔ)體介導(dǎo)的慢性血液疾病，此前治療依賴靜脈注射抗C5抗體（如依庫(kù)珠單抗）。
伊普可泮通過(guò)精準(zhǔn)調(diào)控補(bǔ)體旁路激活，可潛在應(yīng)用于年齡相關(guān)性黃斑變性、非典型溶血尿毒綜合征及C3腎小球病等多種補(bǔ)體相關(guān)疾病，相關(guān)適應(yīng)癥尚在臨床開發(fā)中。其口服給藥方式顯著提升患者用藥便利性，成為補(bǔ)體靶向治療領(lǐng)域的重要突破。
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. |