Go 6976
(Synonyms: 5,6,7,13-四氢-13-甲基-5-氧代-12H-吲哚并[2,3-A]吡咯并[3,4-C]咔唑-12-丙腈,Go6976;Go-6976) 目录号 : GC15564
Go 6976 是一种有效的蛋白激酶(PKs)抑制剂，对PKC、cGMP依赖性蛋白激酶和肌球蛋白轻链激酶的IC50值分别为0.02µM、6.2µM和5.8µM。
Cas No.:136194-77-9
Sample solution is provided at 25 µL, 10mM.
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Go 6976 is a potent inhibitor of protein kinases (PKs), with IC50 values of 0.02µM, 6.2µM, and 5.8µM for PKC, cGMP-dependent protein kinase, and myosin light-chain kinase, respectively[1]. Go 6976 blockes neurotrophin-induced signaling and autophosphorylation of neurotrophin-specific tyrosine kinase receptors[2]. Go 6976 has been widely used as an anticancer agent to inhibit FLT3 kinase activity and block leukemic cell growth[3].
In vitro, Go 6976 treatment at 100nM for 48 hours significantly inhibited the invasion of T24 cells[4]. Treatment of 5637 cells with 1µM Go 6976 for 24 hours significantly promoted apoptotic cell death and induced asynchronous cell mitosis[5]. Treatment with 300µM of Go 6976 for 1 hour reversed hyperglucose-induced insulin resistance in adipocytes[6].
In vivo, Go 6976 treatment via intraperitoneal injection at a single dose of 2.5mg/kg 30min before lipopolysaccharide (LPS)/D-galactosamine (d-GalN) administration improved mouse survival and alleviated liver injury[7]. Intraperitoneal injection of Go 6976 at a dose of 2mg/kg/day for 1 week significantly improved renal injury and reduced the area of fibrosis in a mouse model of unilateral ureteral obstruction (UUO)[8].
References:
[1] Qatsha K A, Rudolph C, Marmé D, et al. Gö 6976, a selective inhibitor of protein kinase C, is a potent antagonist of human immunodeficiency virus 1 induction from latent/low-level-producing reservoir cells in vitro[J]. Proceedings of the National Academy of Sciences, 1993, 90(10): 4674-4678.
[2] Behrens M M, Strasser U, Choi D W. Gö 6976 Is a Potent Inhibitor of Neurotrophin‐Receptor Intrinsic Tyrosine Kinase[J]. Journal of neurochemistry, 1999, 72(3): 919-924.
[3] Yoshida A, Zokumasu K, Ueda T. Go6976, a Potent FLT3 Kinase Inhibitor, Exerts Antiproliferative Activity Against Acute Myeloid Leukemia Via Inhibition Of Survivin and Mcl-1 In The Presence Of Human Serum[J]. Blood, 2013, 122(21): 3839.
[4] Koivunen J, Aaltonen V, Koskela S, et al. Protein kinase C α/β inhibitor Go6976 promotes formation of cell junctions and inhibits invasion of urinary bladder carcinoma cells[J]. Cancer research, 2004, 64(16): 5693-5701.
[5] Aaltonen V, Koivunen J, Laato M, et al. PKC inhibitor Go6976 induces mitosis and enhances doxorubicin-paclitaxel cytotoxicity in urinary bladder carcinoma cells[J]. Cancer letters, 2007, 253(1): 97-107.
[6] Robinson K A, Hegyi K, Hannun Y A, et al. Go-6976 reverses hyperglycemia-induced insulin resistance independently of cPKC inhibition in adipocytes[J]. Plos one, 2014, 9(10): e108963.
[7] Duan G J, Zhu J, Xu C Y, et al. Protective effect of Gö6976, a PKD inhibitor, on LPS/d-GalN-induced acute liver injury in mice[J]. Inflammation research, 2011, 60(4): 357-366.
[8] Xue X, Ren J, Sun X, et al. Protein kinase Cα drives fibroblast activation and kidney fibrosis by stimulating autophagic flux[J]. Journal of Biological Chemistry, 2018, 293(28): 11119-11130.
Go 6976 是一种有效的蛋白激酶(PKs)抑制剂，对PKC、cGMP依赖性蛋白激酶和肌球蛋白轻链激酶的IC50值分别为0.02µM、6.2µM和5.8µM[1]。Go 6976能阻断神经营养因子诱导的信号传导以及神经营养因子特异性酪氨酸激酶受体的自磷酸化[2]。Go 6976 已被广泛用作抗癌剂，以抑制FLT3激酶活性并阻断白血病细胞生长[3]。
在体外，用100nM的Go 6976处理T24细胞48小时能显著抑制细胞侵袭[4]。用1µM的Go 6976处理5637细胞24小时，能显著促进细胞凋亡性死亡并诱导非同步有丝分裂[5]。用300µM的Go 6976处理脂肪细胞1小时，可逆转高糖诱导的胰岛素抵抗[6]。
在体内，于注射脂多糖(LPS)/D-半乳糖胺(d-GalN)前30分钟，单次腹腔注射2.5mg/kg剂量的Go 6976，能提高小鼠存活率并减轻肝损伤[7]。在小鼠单侧输尿管梗阻(UUO)模型中，以2mg/kg/day的剂量腹腔注射Go 6976一周，能显著改善肾损伤并减少纤维化面积[8]。
| Cell experiment [1]: | |
Cell lines | 5637 cells |
Preparation Method | 1.5×106 5637 cells were seeded in DMEM medium without fetal bovine serum (FCS) and supplemented with Go 6976 (100nM) and then seeded in invasion chambers. The invasion chambers were placed on DMEM medium containing 10% FCS and Go 6976. Forty-eight hours after inoculation, cell invasion was analyzed by counting the number of cells that had passed through the invasion chamber. |
Reaction Conditions | 100nM; 48h |
Applications | Go 6976 treatment almost completely blocked the invasion of 5637 cells. |
| Animal experiment [2]: | |
Animal models | Balb/c mice |
Preparation Method | Balb/c mice (6-8 weeks old; body weight 20-22g) were housed under controlled conditions (temperature 22°C, humidity 55%, 12-h circadian rhythm) and fed standard laboratory diets. Mice were intraperitoneally injected with Go 6976 (2.5mg/kg, dissolved in DMSO) or an equal volume of solvent, and 30min later, LPS (50μg/kg) and d-GalN (800mg/kg) were injected intraperitoneally, and liver samples were collected 6h later for analysis. |
Dosage form | 2.5mg/kg for once; i.p. |
Applications | Go 6976 treatment significantly reduced liver damage and inflammatory cell infiltration in mice. |
References: | |
| Cas No. | 136194-77-9 | SDF | |
| 别名 | 5,6,7,13-四氢-13-甲基-5-氧代-12H-吲哚并[2,3-A]吡咯并[3,4-C]咔唑-12-丙腈,Go6976;Go-6976 | ||
| 化学名 | 3-(13-methyl-5-oxo-6,7-dihydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12(13H)-yl)propanenitrile | ||
| Canonical SMILES | O=C1NCC2=C3C(N(CCC#N)C4=CC=CC=C34)=C5N(C)C6=CC=CC=C6C5=C21 | ||
| 分子式 | C24H18N4O | 分子量 | 378.43 |
| 溶解度 | DMF: 10 mg/ml,DMF:PBS (pH 7) (1:10): 0.1 mg/ml,DMSO: 10 mg/ml | 储存条件 | Store at -20°C,protect from light |
| General tips | 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 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.6425 mL | 13.2125 mL | 26.425 mL |
| 5 mM | 528.5 μL | 2.6425 mL | 5.285 mL |
| 10 mM | 264.2 μL | 1.3212 mL | 2.6425 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
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，
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 saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Quality Control & SDS
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- Purity: >98.00%
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