MK-5108

SKU: orb1689348

Description

MK-5108 (VX-689) is a highly selective, sub-nanomolar inhibitor of Aurora-A kinase (IC50 = 0.064 nM). It is widely used in cancer research to study mitotic progression and has demonstrated antitumor activity in both cellular assays and in vivo xenograft models.

Research Area

Cell Biology, Epigenetics & Chromatin

Key Properties

• CAS Number: 1010085-13-8
• MW: 461.94
• Purity: >99.99% (May vary between batches)
• Formula: C₂₂H₂₁ClFN₃O₃S
• SMILES: OC(=O)[C@@]1(Cc2cccc(Nc3nccs3)n2)CC[C@@H](CC1)Oc1cccc(Cl)c1F
• Target: Aurora Kinase,Autophagy
• Solubility: DMSO:50 mg/mL (108.24 mM);H2O:< 1 mg/mL (insoluble or slightly soluble);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (4.33 mM);Ethanol:< 1 mg/mL (insoluble or slightly soluble)

Bioactivity

• Target IC50:
  Aurora A:0.064 nM
• In Vivo:
  MK-5108 induces pHH3-positive cells at doses of 16 mg/kg and 32 mg/kg. Plasma concentration of MK-5108 at 8 mg/kg and 16 mg/kg are 1.7 μM and 4.4 μM, respectively. MK-5108 treatment results in the induction of pHH3 in tumor and skin tissues, which starts at 2 hours and reachs a maximum at 4 hours. MK-5108 treatments at 15 mg/kg and 30 mg/kg results in significant tumor growth inhibition with the change in mean tumor volume for the treatment group as a percentage of the mean change in the control group (%T/C) of 10% and 6% at day 11, and 17% and 5% at day 18, respectively. MK-5108 is well tolerated at both doses, with minimal reduction in body weight. MK-5108 also exhibits significant antitumor activity through intermittent dosing in nude rats bearing SW48 tumors, MK-5108 at 15 mg/kg and 45 mg/kg causes dose-dependent tumor growth inhibition with a %T/C of 35% and 7% at day 10, and 58% and 32% at day 27, respectively.
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• In Vitro:
  MK-5108 inhibits Aurora-A activity in an ATP-competitive manner. MK-5108 shows robust selectivity against the other family kinases Aurora-B (220-fold) and Aurora-C (190-fold) in the biochemical assay. MK-5108 also reveals high selectivity for Aurora-A over other protein kinases. MK-5108 inhibits only one kinase (TrkA) with <100-fold selectivity. MK-5108 may be more Aurora-A selective than MLN8054. Consistent with the induction of pHH3-positive cells, MK-5108 induces accumulation of cells in the G2-M phase. MK-5108 inhibits the proliferation of tumor cells including HCC1143, AU565, MCF-7, HCC1806 and CAL85-1 with an IC50 of 0.42 μM, 0.45 μM, 0.52 μM, 0.56 μM and 0.74 μM, respectively. MK-5108 decreases cell viability in a dose-dependent fashion in all three cell lines including LEIO285, LEIO505 and SK-LSM1 cells with an IC50 of approximately 100 nM. Incubation with MK-5108 in LEIO285 increases the proportion of cells in G2/M at 48 and 72 hours post-treatment. MK-5108 significant increases in Caspase 3/7 activity when compared to DMSO-treated control cultures at both time points. In LEIO505 cells, MK-5108 leads to more cells accumulating at G2/M phases at 24 hours but not 48 hours or 72 hours. MK-5108 arrests ULMS cell lines at M phase MK-5108 decreases the IC50 of gemcitabine in LEIO285 cells, but increases IC50 of gemcitabine in LEIO505 and SK-LMS1 cells.
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• Cell Research:
  HeLa-S3 cells are synchronized at the G1-S phase boundary by double thymidine block with 2 mM thymidine. Cells are washed and seeded to 96-well cell culture plates. After 4 hours, an equal volume of medium containing MK-5108 is added to each well. Nocodazole (300 nM) is used as a 100% control. The cells are fixed overnight with cold methanol 12 hours after seeding. Then, the cells are stained with rabbit anti-phospho-histone H3 Ser28 antibody and then with anti-rabbit IgG-Cy5. Total nuclei are stained with 10 mg/mL 4′,6-diamidino-2-phenylindole. Immunostained images are acquired using the IN Cell Analyzer1000 with ×10 objective lens. After acquisition of images, data are analyzed. The %pHH3-positive index is determined by measuring the %pHH3-positive cell counts per total nuclei counts for each sample, then by normalizing with respect to nocodazole-treated cells. (Only for Reference)
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Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

inhibit, MK 5108, MK5108, MK-5108, Inhibitor, Autophagy, AuroraKinase, Aurora A, Aurora Kinase, VX 689, VX689, VX-689

Compound Identifiers

PubChem CID

24748204