CYC116

Catalog No.S1171 Batch:S117103

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Technical Data

Formula

C18H20N6OS
Molecular Weight 368.46 CAS No. 693228-63-6
Solubility (25°C)* In vitro DMSO 37 mg/mL (100.41 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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description CYC116 is a potent inhibitor of Aurora A/B with Ki of 8.0 nM/9.2 nM, is less potent to VEGFR2 (Ki 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.
Targets
Aurora A [1]
(Cell-free assay)		 Aurora B [1]
(Cell-free assay)		 VEGFR2 [1]
(Cell-free assay)		 FLT3 [1]
(Cell-free assay)		 CDK2/CyclinE [1]
(Cell-free assay)		 View More
8 nM(Ki) 9 nM(Ki) 44 nM(Ki) 44 nM(Ki) 0.39 μM(Ki)
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]
Features An orally bioavailable, small molecule inhibitor of Aurora kinase/VEGFR2.

Protocol (from reference)

Kinase Assay:[1]
  • Kinase Assays

    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.
Cell Assay:

[1]
  • Cell lines

    HeLa, MCF7, MV4-11 and A2780 cells

  • Concentrations

    0-10 μM

  • Incubation Time

    72 or 96 hours

  • Method

    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.
Animal Study:

[1]
  • Animal Models

    NCI-H460 cells are implanted intraperitoneally into the mice.

  • Dosages

    75 and 100 mg/kg

  • Administration

    Administered via p.o.

Customer Product Validation

Data independently produced by Dr Zhang of Tianjin Medical University,

Selleck's CYC116 has been cited by 10 publications

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

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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