GDC-2394|cas:2238822-07-4|西域试剂

GDC-2394,98.36%

产品编号：Bellancom-148258| CAS NO：2238822-07-4| 分子式：C₂₀H₂₅N₅O₄S| 分子量：431.51

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货号	包装	价格	库存与货期	购买量	操作
Bellancom-148258		￥1500.00	杭州北京（现货）
Bellancom-148258		￥5100.00	杭州北京（现货）

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GDC-2394

产品介绍

GDC-2394 是一种口服有效、选择性的 NLRP3 抑制剂，同时也抑制 IL-1β，IC₅₀ 为 0.4 μM (human IL-1β) 和 0.1 μM (mouse IL-1β)。GDC-2394 抑制 NLRP3 诱导的 caspase-1 活性，但不抑制 NLRC4 依赖的炎症小体激活。

生物活性

GDC-2394 is an orally active and selective NLRP3 inhibitor, and also inhibits IL-1β with IC₅₀s of 0.4 μM (human IL-1β) and 0.1 μM (mouse IL-1β). GDC-2394 inhibits NLRP3-induced caspase-1 activity without inhibiting NLRC4-dependent inflammasome activation.

体外研究

GDC-2394 (20 μM; 30 min) inhibits NLRP3-induced apoptosis associated speck-like protein containing CARD (ASC) speck formation in THP-1 cells.
GDC-2394 (1 nM-10 μM; 7 d) inhibits human macrophage IL-1β and IL-18 production after activation of the NLRP3 inflammasome.
GDC-2394 (0-20 μM; 30 min) inhibits NLRP3-dependent caspase-1 activation (IC₅₀=51 nM) in THP-1 cells, also inhibits NLRP3-dependent IL-1β release (IC₅₀=63 nM) and NLRC4-dependent IL-1β release (IC₅₀>20 μM) in mouse bone marrow-derived macrophages (mBMDMs).

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

体内研究

GDC-2394 (compound 20) (1 mg/kg, 10 mg/kg; p.o.; single dose) inhibits production of IL-1β in an acute mouse peritonitis model.
GDC-2394 (25 mg/kg; once daily for 7 d) reduces paw swelling and pain in a functional rat model of gouty arthritis.

Preclinical PK of GDC-2394.

Species	Mouse	Rat	Dog	Cyno
CL_p (mL/min/kg)	10.1	1.3	11.7	4.1
V_ss (L/kg)	0.72	0.29	0.67	0.18
T_1/2 (h)	1.2	4.4	0.99	0.89
%F (1 mg/kg)	80	33	78	53

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	Acute mouse peritonitis model
Dosage:	1 mg/kg and 10 mg/kg
Administration:	Oral gavage; 2 h later treated with 1.25 μg LPS (i.p.) followed by 1 mg monosodium urate crystals (i.p.) a further 2 h later.
Result:	Resulted in a dose-dependent decrease in peritoneal IL-1β concentrations after MSU treatment, and decreased the level of IL-1β by 66.8 and 81.3% at 1 and 10 mg/kg compared with the control.

Animal Model:	Functional rat model of gouty arthritis
Dosage:	25 mg/kg
Administration:	Interventional injection; once daily for 7 days
Result:	Significantly inhibited knee swelling after 48 h.

体内研究

Species	Mouse	Rat	Dog	Cyno
CL_p (mL/min/kg)	10.1	1.3	11.7	4.1
V_ss (L/kg)	0.72	0.29	0.67	0.18
T_1/2 (h)	1.2	4.4	0.99	0.89
%F (1 mg/kg)	80	33	78	53

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	Acute mouse peritonitis model
Dosage:	1 mg/kg and 10 mg/kg
Administration:	Oral gavage; 2 h later treated with 1.25 μg LPS (i.p.) followed by 1 mg monosodium urate crystals (i.p.) a further 2 h later.
Result:	Resulted in a dose-dependent decrease in peritoneal IL-1β concentrations after MSU treatment, and decreased the level of IL-1β by 66.8 and 81.3% at 1 and 10 mg/kg compared with the control.

Animal Model:	Functional rat model of gouty arthritis
Dosage:	25 mg/kg
Administration:	Interventional injection; once daily for 7 days
Result:	Significantly inhibited knee swelling after 48 h.

性状

Solid

溶解性数据

In Vitro:

DMSO : 50 mg/mL (115.87 mM; ultrasonic and warming and heat to 60°C)

配制储备液

浓度溶剂体积质量	1 mg	5 mg	10 mg

1 mM	2.3174 mL	11.5872 mL	23.1744 mL
5 mM	0.4635 mL	2.3174 mL	4.6349 mL
10 mM	0.2317 mL	1.1587 mL	2.3174 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°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 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 (4.82 mM); Clear solution

此方案可获得 ≥ 2.08 mg/mL (4.82 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。
将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液
2.

请依序添加每种溶剂： 10% DMSO 90% (20% SBE-β-CD in saline)
Solubility: ≥ 2.08 mg/mL (4.82 mM); Clear solution

此方案可获得 ≥ 2.08 mg/mL (4.82 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 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。
将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
3.

请依序添加每种溶剂： 10% DMSO 90% corn oil
Solubility: ≥ 2.08 mg/mL (4.82 mM); Clear solution

此方案可获得 ≥ 2.08 mg/mL (4.82 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。