Onvansertib (NMS-P937)

製品コードS7255 バッチS725505

化学情報

	Synonyms	PCM-075, NMS1286937	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₂₄H₂₇F₃N₈O₃
	分子量	532.52	CAS No.	1034616-18-6
Solubility (25°C)*	体外	DMSO	50 mg/mL warmed with 50ºC water bath (93.89 mM)
		Ethanol	2 mg/mL warmed with 50ºC water bath (3.75 mM)
		Water	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	Onvansertib (NMS-P937, PCM-075, NMS1286937) is an orally available, selective Polo-like Kinase 1 (PLK1) inhibitor with IC50 of 2 nM, 5000-fold selectivity over PLK2/PLK3. Onvansertib (NMS-P937) potently causes a mitotic cell-cycle arrest followed by apoptosis in cancer cell lines and inhibits tumor growth. Phase 1.
in vitro	NMS-P937 shows a broad-spectrum antiproliferative activity against different solid tumor, leukemias and lymphomas cell lines. NMS-P937 potently causes a mitotic cell-cycle arrest followed by apoptosis in A2780 cells. ^[2]
in vivo	In mice xenografted with human HCT116 colon adenocarcinoma cells, NMS-P937 (90 mg/kg/d i.v. or p.o.) shows a significant tumor growth inhibition. ^[1] In mice bearing HT29, Colo205 colorectal, or A2780 ovarian xenograft tumors, NMS-P937 inhibits xenograft tumor growth. In addition, NMS-P937, in combination with approved cytotoxic drugs, causes enhanced tumor regression, and prolongs survival of animals. ^[2]

製品説明

Onvansertib (NMS-P937, PCM-075, NMS1286937) is an orally available, selective Polo-like Kinase 1 (PLK1) inhibitor with IC50 of 2 nM, 5000-fold selectivity over PLK2/PLK3. Onvansertib (NMS-P937) potently causes a mitotic cell-cycle arrest followed by apoptosis in cancer cell lines and inhibits tumor growth. Phase 1.

in vitro

NMS-P937 shows a broad-spectrum antiproliferative activity against different solid tumor, leukemias and lymphomas cell lines. NMS-P937 potently causes a mitotic cell-cycle arrest followed by apoptosis in A2780 cells. ^[2]

in vivo

In mice xenografted with human HCT116 colon adenocarcinoma cells, NMS-P937 (90 mg/kg/d i.v. or p.o.) shows a significant tumor growth inhibition. ^[1]

In mice bearing HT29, Colo205 colorectal, or A2780 ovarian xenograft tumors, NMS-P937 inhibits xenograft tumor growth. In addition, NMS-P937, in combination with approved cytotoxic drugs, causes enhanced tumor regression, and prolongs survival of animals. ^[2]

プロトコル(参考用のみ)

キナーゼアッセイ	Kinase profile
キナーゼアッセイ	The inhibitory activity of putative kinase inhibitors and the potency of selected compounds are determined using a trans-phosphorylation assay. Specific peptide or protein substrates are trans-phosphorylated by their specific serine-threonine or tyrosine kinase, in the presence of ATP traced with ³³P-γ-ATP, at optimized buffer and cofactors conditions. At the end of the phosphorylation reaction, more than 98% unlabeled ATP and radioactive ATP is captured by adding an excess of the ion exchange dowex resin; the resin then settles down to the bottom of the reaction plate by gravity. Supernatant, containing the phosphorylated substrate, is subsequently withdrawn and transferred into a counting plate, followed by evaluation by b-counting. Inhibitory potency evaluation for all the tested kinases was performed at 25 °C using a 60 min end-point assay where the concentrations of ATP and substrates are kept equal to 2 x αKm and saturated (>5 x αKm), respectively.
細胞アッセイ	細胞株	137 solid tumor cell lines, and 43 cell lines derived from leukemias and lymphomas
	濃度	~10 μM
	反応時間	72 hours
	実験の流れ	Cells are seeded into 96- or 384-well plates at densities ranging from 10,000 to 30,000/cm2 for adherent and 100,000/mL for nonadherent cells in appropriate medium supplemented with 10% fetal calf serum. After 24 hours, cells were treated in duplicate with serial dilutions of NMS-P937, and 72 hours later, the viable cell number was assessed by the CellTiter-Glo Assay (Promega). IC50 values were calculated with a sigmoidal fitting algorithm (Assay Explorer MDL). Experiments were carried out independently at least twice.
動物実験	動物モデル	CD1 nu/nu mice xenografted with human HCT116 colon adenocarcinoma cells
	投薬量	45 mg/kg bid (i.v.); 90 mg/kg daily (p.o.)
	投与方法	i.v. or p.o.

参考

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Onvansertib inhibits the proliferation and improves the cisplatin-resistance of lung adenocarcinoma via β-catenin/c-Myc signaling pathway [ Am J Cancer Res, 2023, 13(2):623-637]	PubMed: 36895968
CSE1L is a negative regulator of the RB-DREAM pathway in p53 wild-type NSCLC and can be targeted using an HDAC1/2 inhibitor [ Sci Rep, 2023, 13(1):16271]	PubMed: 37759078
Development of a nanoparticle-based immunotherapy targeting PD-L1 and PLK1 for lung cancer treatment [ Nat Commun, 2022, 13(1):4261]	PubMed: 35871223
Development of a nanoparticle-based immunotherapy targeting PD-L1 and PLK1 for lung cancer treatment [ Nat Commun, 2022, 13(1):4261]	PubMed: 35871223
The Polo-like kinase 1 inhibitor onvansertib represents a relevant treatment for head and neck squamous cell carcinoma resistant to cisplatin and radiotherapy [ Theranostics, 2021, 11(19):9571-9586]	PubMed: 34646387
Single-cell RNA-seq highlights intra-tumoral heterogeneity and malignant progression in pancreatic ductal adenocarcinoma. [ Cell Res, 2019, 29(9):725-738]	PubMed: 31273297
BI-2536 and BI-6727, dual Polo-like kinase/bromodomain inhibitors, effectively reactivate latent HIV-1. [ Sci Rep, 2018, 8(1):3521]	PubMed: 29476067

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。