SCH772984
(Synonyms: (R)-1-(2--2-氧(4-(4-(嘧啶-2-基)苯基)对二氮己环-1-基)乙基)-N-(3-(吡啶-4-基)-1H--5INDAZOL-基)吡咯烷-3-甲酰胺,SCH 772984;SCH-772984) 目录号 : GC16001A selective inhibitor of ERK1/2
Cas No.:942183-80-4
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cell experiment [1]: | |
Cell lines |
melanoma cell lines (M408, M202, WM1366) |
Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
Reaction Conditions |
24 h; 500 nM |
Applications |
Treatment with SCH772984 for the sensitive M408 resulted in decreased pRSK, disappearance of pERK1/2, and slight induction of pMEK, with no change in total RSK, MEK, ERK 1/2, or AKT. For the resistant M202, a modest induction of pMEK with some decrease in pERK and pRSK was observed at 24 hours. Treatment with SCH772984 resulted in upregulation of pAKT levels for M408 and WM1366. |
Animal experiment [2]: | |
Animal models |
Nude mice |
Dosage form |
25 mg/kg; b.i.d; intraperitoneal injection |
Applications |
The therapeutic effects of combining the CDK inhibitor Dinaciclib with inhibitors of ERK inhibitor SCH772984 were evaluated using two orthotopic patient-derived human pancreatic cancer xenograft models (Panc253 and Panc265). These models closely resemble the physiological and pathological conditions of pancreatic cancer in humans. A 2-3 mm3 tumor explant was implanted into the pancreas of nude mice and ultrasound imaging was used to measure the tumor size (3D) before randomization and treatment, which began when tumors grew to 50-100 mm3. The combination of Dinaciclib (20 mg/kg, i.p., t.i.w.) and SCH772984 (25 mg/kg, i.p., b.i.d.) dramatically inhibited the growth of primary orthotopic Panc265 (82.5%, p < 0.001) and Panc253 (95.7%, p <0.001) versus control, and also the number of metastatic lesions of both Panc265 (94.9%, p <0.001) and Panc253 (92.4%, p <0.02). |
Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
References: [1] Wong D J L, Robert L, Atefi M S, et al. Antitumor activity of the ERK inhibitor SCH722984 against BRAF mutant, NRAS mutant and wild-type melanoma[J]. Molecular cancer, 2014, 13(1): 194. [2] Hu C, Dadon T, Chenna V, et al. Abstract B263: Combined inhibition of cyclin-dependent kinases (Dinaciclib) and AKT (MK-2206) or ERK (SCH772984) dramatically blocks pancreatic tumor growth and metastases in patient-derived orthotopic xenograft models[J]. Molecular Cancer Therapeutics, 2013, 12(11 Supplement): B263-B263. |
SCH772984, identified by an affinity-based mass spectroscopy high-throughput platform, is a novel, potent and ATP-competitive inhibition of ERK1 and ERK2 with 50% inhibition concentration IC50 values of 4 nmol/L and 1 nmol/L respectively. Although it displays behaviors of both type I and type II kinase inhibitors, SCH772984 is highly selective against only seven kinases, including CLK2, FLT4, GSG2, MAP4K4, MAPK1, MINK1, PRKD1 and TTK, out of a wide range of 300 tested with more than 50% inhibition at a concentration of 1 μmol/L. Study results have shown that SCH772984 potently inhibits tumor cells with mutations in BRAF, NRAS and KRAS at nanomolar concentrations.
SCH772984是一种新型、强效且具有ATP竞争性的ERK1和ERK2抑制剂,其50%抑制浓度IC50分别为4 nmol/L和1 nmol/L。虽然它表现出类型I和类型II激酶抑制剂的特性,但SCH772984对仅有七种激酶具有高度选择性,包括CLK2、FLT4、GSG2、MAP4K4、MAPK1、MINK1、PRKD1和TTK,在1 μmol/L浓度下对这些激酶的抑制率超过50%。研究结果表明,SCH772984在纳摩尔级浓度下强烈抑制具有BRAF、NRAS和KRAS突变的肿瘤细胞。
Reference
[1].Morris EJ, Jha S, Restaino CR, Dayananth P, Zhu H, Cooper A, Carr D, Deng Y, Jin W, Black S, Long B, Liu J, Dinunzio E, Windsor W, Zhang R, Zhao S, Angagaw MH, Pinheiro EM, Desai J, Xiao L, Shipps G, Hruza A, Wang J, Kelly J, Paliwal S, Gao X, Babu BS, Zhu L, Daublain P, Zhang L, Lutterbach BA, Pelletier MR, Philippar U, Siliphaivanh P, Witter D, Kirschmeier P, Bishop WR, Hicklin D, Gilliland DG, Jayaraman L, Zawel L, Fawell S, Samatar AA. Discovery of a novel ERK inhibitor with activity in models of acquired resistance to BRAF and MEK inhibitors. Cancer Discov. 2013 Jul;3(7):742-750
Cas No. | 942183-80-4 | SDF | |
别名 | (R)-1-(2--2-氧(4-(4-(嘧啶-2-基)苯基)对二氮己环-1-基)乙基)-N-(3-(吡啶-4-基)-1H--5INDAZOL-基)吡咯烷-3-甲酰胺,SCH 772984;SCH-772984 | ||
化学名 | (3R)-1-[2-oxo-2-[4-(4-pyrimidin-2-ylphenyl)piperazin-1-yl]ethyl]-N-(3-pyridin-4-yl-1H-indazol-5-yl)pyrrolidine-3-carboxamide | ||
Canonical SMILES | C1CN(CC1C(=O)NC2=CC3=C(C=C2)NN=C3C4=CC=NC=C4)CC(=O)N5CCN(CC5)C6=CC=C(C=C6)C7=NC=CC=N7 | ||
分子式 | C33H33N9O2 | 分子量 | 587.67 |
溶解度 | ≥ 14.7 mg/mL in DMSO with gentle warming | 储存条件 | Store at -20°C |
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 | |||
1 mg | 5 mg | 10 mg | |
1 mM | 1.7016 mL | 8.5082 mL | 17.0164 mL |
5 mM | 0.3403 mL | 1.7016 mL | 3.4033 mL |
10 mM | 0.1702 mL | 0.8508 mL | 1.7016 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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。