NMS-1286937
(Synonyms: 4,5-二氢-1-(2-羟基乙基)-8-[[5-(4-甲基-1-哌嗪基)-2-(三氟甲氧基)苯基]氨基]-1H-吡唑并[4,3-H]喹唑啉-3-甲酰胺,NMS-1286937; NMS-P937) 目录号 : GC12515
NMS-1286937是一种口服有效的小分子化合物，能够高效且选择性地抑制Polo样激酶1（PLK1）的活性，半数抑制浓度（IC50）为2nM。
Cas No.:1034616-18-6
Sample solution is provided at 25 µL, 10mM.
_1-3.$$$39978408@51.jpg');)
_1-9.$$$38538795@65.jpg');)
_1-9.$$$39112701@51.jpg');)
_1-7.$$$37316672@70.jpg');)
_366-372.$$$36198801@70.jpg');)
.$$$38565142@65.jpg');)
_1867-1883.$$$33248023@67.jpg');)
_eads6055.$$$39977546@45.jpg');)
_eadm9805.$$$40080571@45.jpg');)
_eadj3020.$$$39666821@45.jpg');)
_1-20.$$$39757301@28.jpg');)
_1-24.$$$38898113@28.jpg');)
_273-287.$$$36806353@46.jpg');)
_1-16.$$$37156877@44.jpg');)
_1-19.$$$37460805@44.jpg');)
_1291-1307.$$$34518654@46.jpg');)
NMS-1286937 is an orally active small-molecule compound. NMS-1286937 potently and selectively inhibits Polo-like kinase 1 (PLK1) activity with a half-maximal inhibitory concentration (IC50) of 2nM[1]. By competitively binding to the ATP site, NMS-1286937 reversibly inhibits PLK1, leading to G2/M phase cell cycle arrest, chromosomal misalignment, and abnormal spindle formation in various tumor cells, ultimately resulting in apoptosis[2]. NMS-1286937 shows potential in the treatment of solid tumors and hematological malignancies[3-4].
In vitro, treatment of medulloblastoma cell lines (D425, D458) with NMS-1286937 (10–20nM) for 24–48 hours induced G2/M phase cell cycle arrest and significantly inhibited cell proliferation and stem cell self-renewal capacity[5]. In ovarian cancer cell lines (Ovcar-3, ES-2), treatment with NMS-1286937 (30–50nM) for 24–72 hours suppressed cell proliferation while activating apoptosis and DNA damage pathways[6].
In vivo, daily oral administration of NMS-1286937 (25mg/kg) for four weeks in LKB1fl/fl p53fl/fl transgenic endometrial cancer model mice significantly inhibited tumor growth and reduced tumor weight[7]. In nude mice bearing patient-derived xenografts (PDX) of platinum-resistant ovarian cancer, once-weekly intravenous administration of NMS-1286937 (50mg/kg) in combination with Paclitaxel (15mg/kg) significantly extended median survival and induced mitotic arrest and DNA damage in tumor tissues[8].
References:
[1] Valsasina B, Beria I, Alli C, et al. NMS-P937, an orally available, specific small-molecule polo-like kinase 1 inhibitor with antitumor activity in solid and hematologic malignancies. Mol Cancer Ther. 2012 Apr;11(4):1006-16.
[2] Su S, Chhabra G, Singh CK, et al. PLK1 inhibition-based combination therapies for cancer management. Transl Oncol. 2022 Feb;16:101332.
[3] Ahn DH, Barzi A, Ridinger M, et al. Onvansertib in Combination with FOLFIRI and Bevacizumab in Second-Line Treatment of KRAS-Mutant Metastatic Colorectal Cancer: A Phase Ib Clinical Study. Clin Cancer Res. 2024 May 15;30(10):2039-2047.
[4] Nouri M, Varkaris A, Ridinger M, et al. AKT Inhibition Sensitizes to Polo-Like Kinase 1 Inhibitor Onvansertib in Prostate Cancer. Mol Cancer Ther. 2024 Oct 1;23(10):1404-1417.
[5] Wang D, Veo B, Pierce A, et al. A novel PLK1 inhibitor onvansertib effectively sensitizes MYC-driven medulloblastoma to radiotherapy. Neuro Oncol. 2022 Mar 12;24(3):414-426.
[6] Chiappa M, Decio A, Guarrera L, et al. Onvansertib treatment overcomes olaparib resistance in high-grade ovarian carcinomas. Cell Death Dis. 2024 Jul 22;15(7):521.
[7] Sinha N, Shen X, Haag J, et al. Onvansertib exhibits anti-proliferative and anti-invasive effects in endometrial cancer. Front Pharmacol. 2025 Mar 17;16:1545038.
[8] Affatato R, Chiappa M, Guffanti F, et al. Onvansertib and paclitaxel combined in platinum-resistant ovarian carcinomas. Ther Adv Med Oncol. 2022 May 31;14:17588359221095064.
NMS-1286937是一种口服有效的小分子化合物，能够高效且选择性地抑制Polo样激酶1（PLK1）的活性，半数抑制浓度（IC50）为2nM[1]。NMS-1286937通过竞争性地结合ATP位点，可逆地抑制PLK1，从而在多种肿瘤细胞中引发G2/M期细胞周期阻滞、染色体错配和纺锤体形成异常，最终导致细胞凋亡[2]。NMS-1286937在实体瘤和血液系统恶性肿瘤的治疗研究中展现出潜力[3-4]。
在体外，NMS-1286937（10–20nM）处理髓母细胞瘤细胞系（D425、D458）24–48小时，可诱导细胞周期的G2/M期细胞周期阻滞，并显著抑制细胞增殖与干细胞自我更新能力[5]。NMS-1286937（10–50nM）处理卵巢癌细胞系（Ovcar-3、ES-2）24–72小时，能够抑制细胞增殖，同时促进细胞凋亡和DNA损伤[6]。
在体内，NMS-1286937（25mg/kg）每日口服给药处理4周，用于LKB1fl/fl p53fl/fl转基因子宫内膜癌模型小鼠。NMS-1286937显著抑制了肿瘤生长并减少肿瘤重量[7]。NMS-1286937（50mg/kg）联合Paclitaxel（15mg/kg）每周一次静脉注射，用于处理移植了铂类耐药卵巢癌患者来源异种移植瘤（PDX）的裸鼠。NMS-1286937与Paclitaxel联合治疗显著延长了荷瘤小鼠的中位生存期，并诱导了肿瘤组织中的有丝分裂阻滞和DNA损伤[8]。
| Cell experiment [1]: | |
Cell lines | Ovcar-3 and ES-2 cells (human ovarian carcinoma cell lines) |
Preparation Method | Cells were cultured in RPMI-1640 or McCoy's 5A medium supplemented with 10% fetal bovine serum (FBS) and maintained at 37°C under 5% CO₂. Cells were treated with NMS-1286937 at concentrations of 10–50nM for 24–72 hours. |
Reaction Conditions | 10-50μM; 24-72h |
Applications | NMS-1286937 induced G₂/M phase cell cycle arrest, with a dose-dependent increase in G₂/M population. |
| Animal experiment [2]: | |
Animal models | NCr-nu/nu mice with patient-derived xenografts (PDXs) of platinum-resistant ovarian carcinomas |
Preparation Method | Mice were orthotopically (intraperitoneally) or subcutaneously transplanted with tumor fragments/cells. NMS-1286937 was administered orally at 50mg/kg for 4 consecutive days per week for 3 weeks, combined with paclitaxel (15mg/kg intravenously once weekly for 3 weeks). Mice were monitored for tumor growth and survival. |
Dosage form | 50mg/kg; p.o.; 4 consecutive days per week for 3 weeks |
Applications | The combination of NMS-1286937 and Paclitaxel significantly prolonged median survival in orthotopic PDX models. Tumor growth inhibition was accompanied by induction of mitotic block (pSer10H3) and DNA damage/apoptosis (γH2AX) in ex vivo tumor tissues. |
References: | |
| Cas No. | 1034616-18-6 | SDF | |
| 别名 | 4,5-二氢-1-(2-羟基乙基)-8-[[5-(4-甲基-1-哌嗪基)-2-(三氟甲氧基)苯基]氨基]-1H-吡唑并[4,3-H]喹唑啉-3-甲酰胺,NMS-1286937; NMS-P937 | ||
| 分子式 | C24H27F3N8O3 | 分子量 | 532.52 |
| 溶解度 | ≥ 13.3mg/mL in DMSO | 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。 |
||
| 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 | 1.8779 mL | 9.3893 mL | 18.7786 mL |
| 5 mM | 375.6 μL | 1.8779 mL | 3.7557 mL |
| 10 mM | 187.8 μL | 938.9 μL | 1.8779 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。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet