CYC116

製品コードS1171 バッチS117102

化学情報

	Synonyms	N/A	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₁₈H₂₀N₆OS
	分子量	368.46	CAS No.	693228-63-6
Solubility (25°C)*	体外	DMSO	25 mg/mL warmed with 50ºC water bath (67.84 mM)
		Water	Insoluble
		Ethanol	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	CYC116 is a potent inhibitor of Aurora A/B with K_i of 8.0 nM/9.2 nM, is less potent to VEGFR2 (K_i of 44 nM), with 50-fold greater potency than CDKs, not active against PKA, Akt/PKB, PKC, no effect on GSK-3α/β, CK2, Plk1 and SAPK2A. Phase 1.
in vitro	The most Aurora-selective CYC116 shows inhibitory effect on Aurora A and B kinases 50-fold more potently than any of the CDKs assayed. ^[1] CYC116 is initially screened against a panel of human leukemia and solid tumor cell lines using an MTT antiproliferative assay. The results show that CYC116 has broad-spectrum antitumor activity and shows specific cytotoxicity against the acute myelogenous leukemia cell line MV4-11 with IC50 of 34 nM. ^[1] In addition, anti-proliferative activity of CYC116 is found to be associated with Aurora A and B modulation such as, inhibition of Aurora autophosphorylation, reduction of histone H3 phosphorylation, polyploidy, followed by cell death, resulting from a failure in cytokinesis. ^[1]
in vivo	Mice bearing subcutaneous NCI-H460 xenografts are given CYC116 orally for 5 days, at dose levels of 75 and 100 mg/kg q.d. It leads to tumor growth delays of 2.3 and 5.8 days, which translated into specific growth delays of 0.32 and 0.81, respectively. ^[1]
特徴	An orally bioavailable, small molecule inhibitor of Aurora kinase/VEGFR2.

プロトコル(参考用のみ)

キナーゼアッセイ	Kinase Assays
キナーゼアッセイ	Aurora A kinase assays are performed using a 25 μL reaction volume (25 mM β-glycerophosphate, 20 mM Tris/HCl, pH 7.5, 5 mM EGTA, 1 mM DTT, 1 mM Na₃VO₄, 10 μg of kemptide (peptide substrate)). Recombinant Aurora A kinase is diluted in 20 mM Tris/HCl, pH 8, containing 0.5 mg/mL BSA, 2.5% glycerol, and 0.006% Brij-35. Reactions are started by the addition of 5 μL Mg/ATP mix (15 mM MgCl₂, 100 μM ATP, with 18.5 kBq γ-³²P-ATP per well) and incubated at 30°C for 30 minutes before termination with 25 μL of 75 mM H₃PO₄. Aurora B kinase assays are performed like Aurora A except that prior to use, Aurora B is activated in a separate reaction at 30°C for 60 minutes with inner centromere protein.
細胞アッセイ	細胞株	HeLa, MCF7, MV4-11 and A2780 cells
	濃度	0-10 μM
	反応時間	72 or 96 hours
	実験の流れ	Standard MTT assays are performed. In short, cells are seeded into 96-well plates according to doubling time and incubated overnight at 37°C. Test compounds are made up in DMSO, a 3-fold dilution series is prepared in 100 μL of cell medium, added to cells (in triplicates) and incubated for 72 or 96 hours at 37°C. MTT is made up as a stock of 5 mg/mL in cell medium, and the solution is filter-sterilized. Medium is removed from the cells followed by a wash with PBS. MTT solution is then added at 20 μL/well and incubated in the dark at 37°C for 4 hours. MTT solution is removed and cells are again washed with 200 μL of PBS. MTT dye is solubilized with 200 μL/well of DMSO by agitation. Absorbance is read at 540 nm and data analyzed using curve-fitting software to determine IC50 values.
動物実験	動物モデル	NCI-H460 cells are implanted intraperitoneally into the mice.
	投薬量	75 and 100 mg/kg
	投与方法	Administered via p.o.

参考

[1] Wang S, et al. J Med Chem. 2010, 53(11), 4367-4378.

カスタマーフィードバック

: Data independently produced by Dr Zhang of Tianjin Medical University,

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：

Inhibition of epigenetic and cell cycle-related targets in glioblastoma cell lines reveals that onametostat reduces proliferation and viability in both normoxic and hypoxic conditions [ Sci Rep, 2024, 14(1):4303]	PubMed: 38383756
DELs enable the development of BRET probes for target engagement studies in cells [ Cell Chem Biol, 2023, 30(8):987-998.e24]	PubMed: 37490918
A screen of repurposed drugs identifies AMHR2/MISR2 agonists as potential contraceptives [ Proc Natl Acad Sci U S A, 2022, 119(15):e2122512119]	PubMed: 35380904
Inhibition of IκB Kinase Is a Potential Therapeutic Strategy to Circumvent Resistance to Epidermal Growth Factor Receptor Inhibition in Triple-Negative Breast Cancer Cells [ Cancers (Basel), 2022, 14(21)5215]	PubMed: 36358633
Using antagonistic pleiotropy to design a chemotherapy-induced evolutionary trap to target drug resistance in cancer. [ Nat Genet, 2020, 52(4):408-417]	PubMed: 32203462
Chemosensitivity and chemoresistance in endometriosis - differences for ectopic versus eutopic cells. [ Reprod Biomed Online, 2019, 10.1016/j.rbmo.2019.05.019]	PubMed: 31377021
An Anti-Cancer Drug Candidate CYC116 Suppresses Type I Hypersensitive Immune Responses through the Inhibition of Fyn Kinase in Mast Cells [ Biomol Ther (Seoul), 2019, 27(3):311-317]	PubMed: 30332888
Targeted Polo-like Kinase Inhibition Combined With Aurora Kinase Inhibition in Pediatric Acute Leukemia Cells. [ J Pediatr Hematol Oncol, 2019, 41(6):e359-e370]	PubMed: 30702467
Aurora Kinases as Druggable Targets in Pediatric Leukemia: Heterogeneity in Target Modulation Activities and Cytotoxicity by Diverse Novel Therapeutic Agents [Jayanthan A, et al. PLoS One, 2014, 9(7):e102741]	PubMed: 25048812
Targeting Sonic Hedgehog-Associated Medulloblastoma through Inhibition of Aurora and Polo-like Kinases. [Markant SL, et al. Cancer Res, 2013, 73(20):6310-22]	PubMed: 24067506

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。

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