| 规格 | 价格 | 库存 | 数量 |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| Other Sizes |
|
| 靶点 |
Stearoyl-CoA desaturase (SCD, including SCD1 and SCD5) (IC50 for human SCD1 enzyme activity: 0.03 μM; IC50 for mouse SCD1 enzyme activity: 0.05 μM) [1]
|
|---|---|
| 体外研究 (In Vitro) |
硬脂酰辅酶去饱和酶 (SCD) 抑制剂 GSK1940029（SCD 抑制剂 1）是一种药物，可用于治疗和/或预防多种疾病，包括由 SCD 酶介导的疾病，例如与血脂水平升高相关的疾病、心血管疾病、糖尿病、肥胖、代谢综合征、痤疮等皮肤病、与癌症相关的疾病或病症，以及与淀粉样斑块形成 Aβ42 肽合成相关的症状的管理（例如阿尔茨海默病）[1]。
1. 抑制SCD酶活性：GSK1940029强效且选择性抑制重组人源和鼠源SCD1的催化活性，脂肪酸去饱和实验显示IC50值分别为0.03 μM（人源）和0.05 μM（鼠源）。该化合物在浓度高达10 μM时，对其他去饱和酶（如Δ6-去饱和酶、Δ5-去饱和酶）无显著抑制作用[1] 2. 抑制细胞中单不饱和脂肪酸（MUFA）合成：在人肝癌HepG2细胞和小鼠3T3-L1脂肪细胞中，GSK1940029剂量依赖性抑制SCD介导的硬脂酸（C18:0）向油酸（C18:1n9）的转化。在0.1 μM浓度下，药物使HepG2细胞中C18:1n9生成减少~70%，3T3-L1细胞中减少~65%，且不影响细胞活力（1 μM时活力>90%）[1] 3. 抑制癌细胞增殖：在SCD依赖性癌细胞系（如MCF-7乳腺癌细胞、A549肺癌细胞）中，GSK1940029抑制细胞增殖，EC50值分别为0.08 μM（MCF-7）和0.12 μM（A549）。流式细胞术分析显示细胞周期停滞在G0/G1期，伴随周期蛋白D1（cyclin D1）表达降低[1] |
| 体内研究 (In Vivo) |
1. 降低小鼠肝脏SCD活性：C57BL/6小鼠口服给予GSK1940029（10 mg/kg、30 mg/kg或100 mg/kg），每日一次，连续7天。肝脏SCD1酶活性呈剂量依赖性抑制，100 mg/kg剂量组最大抑制率~85%。最高剂量组肝脏油酸（C18:1n9）水平降低~60%，硬脂酸（C18:0）水平升高~45%[1]
2. 减轻饮食诱导的小鼠肥胖：高脂饮食（HFD）喂养的C57BL/6小鼠，口服给予GSK1940029（30 mg/kg，每日一次）连续4周。与溶媒对照组相比，治疗组小鼠体重增长减少~20%，附睾脂肪垫重量降低~30%，肝脏甘油三酯水平降低~40%，且进食量无显著变化[1] 3. 改善葡萄糖耐量：在高脂饮食喂养的小鼠中，GSK1940029（30 mg/kg，口服，每日一次）治疗4周后，口服葡萄糖耐量试验（OGTT）显示曲线下面积（AUC）减少~30%，葡萄糖耐量显著改善[1] |
| 酶活实验 |
1. 重组SCD1酶活性实验：纯化重组人源或鼠源SCD1蛋白，重悬于含NADPH、细胞色素b5和ATP（SCD活性辅因子）的实验缓冲液中。将系列浓度的GSK1940029（0.001–1 μM）与酶混合物在37°C下预孵育20分钟，加入[1-¹⁴C]-硬脂酰辅酶A（底物）启动反应，37°C孵育60分钟。加入盐酸-甲醇终止反应，用己烷提取脂肪酸，通过薄层色谱（TLC）分离放射性产物（油酰辅酶A），闪烁计数器定量。绘制酶活性百分比（相对于溶媒对照组）与GSK1940029浓度对数的关系曲线，计算IC50值[1]
|
| 细胞实验 |
1. 细胞SCD活性实验：将HepG2或3T3-L1细胞以2×10⁵个细胞/孔接种到6孔板，过夜培养。用GSK1940029（0.01–1 μM）预处理细胞2小时，再与[1-¹⁴C]-硬脂酸孵育24小时。用氯仿-甲醇提取细胞脂质，脂肪酸甲基化后，通过带放射性检测器的气相色谱（GC）定量硬脂酸（C18:0）向油酸（C18:1n9）的转化[1]
2. 癌细胞增殖实验：将MCF-7或A549细胞以5×10³个细胞/孔接种到96孔板，过夜培养。加入梯度浓度（0.001–1 μM）的GSK1940029，孵育72小时后用比色法检测细胞活力，计算增殖抑制的EC50值。细胞周期分析时，收集细胞用乙醇固定，碘化丙啶（PI）染色，流式细胞术检测[1] |
| 动物实验 |
1. Hepatic SCD inhibition mouse model: Male C57BL/6 mice (6–8 weeks old) were randomly divided into 4 groups (n=6 per group): vehicle control, 10 mg/kg, 30 mg/kg, or 100 mg/kg GSK1940029. The drug was formulated in 0.5% methylcellulose and administered orally via gavage once daily for 7 days. On day 8, mice were euthanized, and livers were excised. Hepatic SCD1 enzyme activity was measured using the recombinant enzyme assay protocol, and fatty acid composition was analyzed by GC [1]
2. Diet-induced obesity mouse model: Male C57BL/6 mice were fed a high-fat diet (60% kcal from fat) for 4 weeks to induce obesity, then randomly divided into vehicle control and GSK1940029 treatment groups (n=8 per group). The drug was administered orally at 30 mg/kg once daily for an additional 4 weeks, with continuous HFD feeding. Body weight was measured weekly, and food intake was recorded daily. At the end of treatment, mice were subjected to an OGTT, then euthanized. Epididymal fat pads and livers were weighed, and hepatic triglyceride levels were quantified using a colorimetric assay [1] |
| 药代性质 (ADME/PK) |
1. Absorption: Oral administration of GSK1940029 (30 mg/kg) in mice results in peak plasma concentrations (Cmax) of ~1.2 μM at 1.5 hours post-dosing. Oral bioavailability is estimated to be ~42% based on comparison of intravenous and oral pharmacokinetic data [1]
2. Distribution: The drug distributes widely to tissues with high SCD expression, including liver, adipose tissue, and lung, with a liver-to-plasma concentration ratio of ~15:1 at 4 hours post-dosing [1] 3. Metabolism: GSK1940029 is metabolized primarily via hepatic cytochrome P450-mediated oxidation, with two major inactive metabolites detected in plasma [1] 4. Excretion: The plasma elimination half-life (t1/2) is ~6.8 hours in mice. Approximately 65% of the administered dose is excreted in feces (40% as unchanged drug, 25% as metabolites) and 20% in urine (primarily as metabolites) within 72 hours [1] |
| 毒性/毒理 (Toxicokinetics/TK) |
1. Acute toxicity: Single oral administration of GSK1940029 at doses up to 500 mg/kg in mice causes no mortality or significant changes in body weight, clinical signs, or organ weights [1]
2. Subchronic toxicity: Four-week oral administration of GSK1940029 (10–100 mg/kg/day) in rats results in no significant hematological, biochemical, or histopathological abnormalities. Mild reductions in serum triglyceride levels are observed, consistent with the drug's mechanism of action [1] 3. Plasma protein binding: In vitro plasma protein binding is ~91% in mouse and human plasma (determined by equilibrium dialysis), with no concentration-dependent binding over the range of 0.1–10 μM [1] |
| 参考文献 | |
| 其他信息 |
1. Drug classification and structure: GSK1940029 is a synthetic 1,2,3-triazole derivative and a selective, reversible inhibitor of stearoyl-CoA desaturase (SCD) [1]
2. Mechanism of action: SCD is a key enzyme in fatty acid metabolism that catalyzes the desaturation of saturated fatty acids (e.g., stearic acid) to monounsaturated fatty acids (e.g., oleic acid). GSK1940029 inhibits SCD activity, leading to depletion of MUFAs, which are essential for lipid synthesis, cell proliferation, and membrane fluidity. This mechanism underlies its effects on obesity, glucose metabolism, and cancer cell growth [1] 3. Therapeutic potential: GSK1940029 is being developed for the treatment of metabolic disorders (e.g., obesity, type 2 diabetes) and SCD-dependent cancers (e.g., breast cancer, lung cancer). Its efficacy in reducing body weight, improving glucose tolerance, and inhibiting cancer cell proliferation supports further clinical development [1] 4. Selectivity: The compound exhibits high selectivity for SCD1 and SCD5 over other fatty acid desaturases and enzymes involved in lipid metabolism, minimizing off-target effects [1] |
| 分子式 |
C18H16CL2N4O2
|
|---|---|
| 分子量 |
391.25124168396
|
| 精确质量 |
390.065
|
| 元素分析 |
C, 55.26; H, 4.12; Cl, 18.12; N, 14.32; O, 8.18
|
| CAS号 |
1150701-66-8
|
| PubChem CID |
42603008
|
| 外观&性状 |
Light yellow to yellow solid powder
|
| 密度 |
1.4±0.1 g/cm3
|
| 折射率 |
1.665
|
| LogP |
2.13
|
| tPSA |
80
|
| 氢键供体(HBD)数目 |
2
|
| 氢键受体(HBA)数目 |
4
|
| 可旋转键数目(RBC) |
5
|
| 重原子数目 |
26
|
| 分子复杂度/Complexity |
476
|
| 定义原子立体中心数目 |
0
|
| SMILES |
ClC(C=CC(CN1N=NC(C(NC2=CC=C(CO)C=C2)=O)=C1C)=C3)=C3Cl
|
| InChi Key |
QQRGSFYTPBYCFD-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C18H16Cl2N4O2/c1-11-17(18(26)21-14-5-2-12(10-25)3-6-14)22-23-24(11)9-13-4-7-15(19)16(20)8-13/h2-8,25H,9-10H2,1H3,(H,21,26)
|
| 化学名 |
1-[(3,4-dichlorophenyl)methyl]-N-[4-(hydroxymethyl)phenyl]-5-methyltriazole-4-carboxamide
|
| 别名 |
GSK1940029; GSK-1940029; GSK 1940029; SCD Inhibitor 1
|
| HS Tariff Code |
2934.99.9001
|
| 存储方式 |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| 运输条件 |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| 溶解度 (体外实验) |
DMSO : ≥ 32 mg/mL (~81.79 mM)
|
|---|---|
| 溶解度 (体内实验) |
注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。
注射用配方
注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)(IP/IV/IM/SC等) *生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。 注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline) 注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil) 示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。 View More
注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)] 口服配方
口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠) 口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素) 示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。 View More
口服配方 3: 溶解于 PEG400 (聚乙二醇400) 请根据您的实验动物和给药方式选择适当的溶解配方/方案： 1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液)); 2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方): 10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline); 假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL； 3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例; 4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶; 5、为保证最佳实验结果，工作液请现配现用！ 6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们; 7、 以上所有助溶剂都可在 Invivochem.cn网站购买。 |
| 制备储备液 | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5559 mL | 12.7796 mL | 25.5591 mL | |
| 5 mM | 0.5112 mL | 2.5559 mL | 5.1118 mL | |
| 10 mM | 0.2556 mL | 1.2780 mL | 2.5559 mL |
1、根据实验需要选择合适的溶剂配制储备液 (母液)：对于大多数产品，InvivoChem推荐用DMSO配置母液 (比如：5、10、20mM或者10、20、50 mg/mL浓度），个别水溶性高的产品可直接溶于水。产品在DMSO 、水或其他溶剂中的具体溶解度详见上”溶解度 (体外)”部分;
2、如果您找不到您想要的溶解度信息，或者很难将产品溶解在溶液中，请联系我们;
3、建议使用下列计算器进行相关计算（摩尔浓度计算器、稀释计算器、分子量计算器、重组计算器等）;
4、母液配好之后，将其分装到常规用量，并储存在-20°C或-80°C，尽量减少反复冻融循环。
计算结果:
工作液浓度： mg/mL；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL)。如该浓度超过该批次药物DMSO溶解度，请首先与我们联系。
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL ddH2O，混匀澄清。
(1) 请确保溶液澄清之后，再加入下一种溶剂 (助溶剂) 。可利用涡旋、超声或水浴加热等方法助溶；
(2) 一定要按顺序加入溶剂 (助溶剂) 。
SCD1 inhibitor-5
SCD1/5-IN-1
Sterculic acid
SSI-4
InvivoChem的所有产品仅用于作科学研究，不面向患者销售
Copyright 2020 InvivoChem LLC | All Rights Reserved 粤ICP备20063088号-1
COA
粤公网安备 44011102003439号
463611831
