LNP023 hydrochloride 是一种有效的,具有口服活性的高选择性的factor B抑制剂。LNP023 直接可逆且高亲和力结合 factor B,KD为 7.9 nM。LNP023 抑制 factor B 的IC50值为 10 nM。
生物活性 | LNP023 hydrochloride is an orally bioavailable, highly potent and highly selectivefactor Binhibitor. LNP023 shows direct, reversible, and high-affinity binding to human factor B with aKDof 7.9 nM. LNP023 inhibits factor B with anIC50value of 10 nM[1][2]. |
IC50& Target | KD: 7.9 nM (factor B)[2] IC50: 10 nM (factor B)[2] |
体外研究 (In Vitro) | LNP023 demonstrates potent inhibition of alternative complement pathway (AP)-induced membrane attack complex (MAC) formation in 50% human serum (IC50value of 130 nM)[2]. LNP023 exhibits excellent selectivity over other proteases affording IC50values of >30 μM across a panel of 41 human proteases, including the AP protein factor D (>100 μM)[3].
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体内研究 (In Vivo) | 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[2]. LNP023 exhibits moderate half-lives (T1/2; Wistar Han rats 3.4 h, beagle dogs 5.5 h) and Cmax(Wistar Han rats 410 nM, beagle dogs 2200 nM) following oral administration (rat 30 and, dog 10 mg/kg)[3]. LNP023 exhibits terminal elimination half-lives (T1/2; 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)[3].
Animal Model: | C57BL/6 mice with KRN-induced arthritis[2] | Dosage: | 20, 60, and 180 mg/kg | Administration: | Orally gavaged; twice a day (b.i.d.) for 14 days | Result: | Blocked KRN-induced arthritis. |
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运输条件 | Room temperature in continental US; may vary elsewhere. |
储存方式 | 4°C, sealed storage, away from moisture *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture) |
溶解性数据 | In Vitro: DMSO : 250 mg/mL(544.69 mM;Need ultrasonic) H2O : 50 mg/mL(108.94 mM;ultrasonic and warming and heat to 60℃) 配制储备液 1 mM | 2.1787 mL | 10.8937 mL | 21.7874 mL | 5 mM | 0.4357 mL | 2.1787 mL | 4.3575 mL | 10 mM | 0.2179 mL | 1.0894 mL | 2.1787 mL |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效。 储备液的保存方式和期限:-80℃, 6 months; -20℃, 1 month (sealed storage, away from moisture)。-80℃ 储存时,请在 6 个月内使用,-20℃ 储存时,请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液,再依次添加助溶剂: ——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议您现用现配,当天使用;
以下溶剂前显示的百 分比是指该溶剂在您配制终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂: 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.08 mg/mL (4.53 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (4.53 mM,饱和度未知) 的澄清溶液。 以 1 mL 工作液为例,取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;向上述体系中加入50 μL Tween-80,混合均匀;然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂: 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 2.08 mg/mL (4.53 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (4.53 mM,饱和度未知) 的澄清溶液。 以 1 mL 工作液为例,取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中,混合均匀。 3. 请依序添加每种溶剂: 10% DMSO 90%corn oil Solubility: ≥ 2.08 mg/mL (4.53 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (4.53 mM,饱和度未知) 的澄清溶液,此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例,取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。 *以上所有助溶剂都可在本网站选购。
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