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MK-5108 CAS: 1010085-13-8

Category: Inhibitors
Product Name: MK-5108
Cat No: I000114
CAS No: 1010085-13-8
Synonyms: VX-689
Molecular Formula: C22H21ClFN3O3S
Molecular Weight: 461.9
SMILES: ClC1=C(F)C(O[C@@H]2CC[C@@](CC3=CC=CC(NC4=NC=CS4)=N3)(C(O)=O)CC2)=CC=C1
InChI: None
Solubility: DMSO: ≤ 6.4 mg/mL (Need warming)
Target: Aurora Kinase
IC50: 0.064 nM
Storage: powder
CAS 1010085-13-8,MK-5108
  • Description

MK-5108 (VX-689) is a highly selective Aurora A inhibitor with IC50 of 0.064 nM; 220- and 190-fold more selective for Aurora A than Aurora B/C. 

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, 0.56μM 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. 

in vivo: 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.

  • Spec

Appearance:Solid powder
Purity: > 98%

  • References

1:A phase I study of MK-5108, an oral aurora a kinase inhibitor, administered both as monotherapy and in combination with docetaxel, in patients with advanced or refractory solid tumors. Amin M, Minton SE, LoRusso PM, Krishnamurthi SS, Pickett CA, Lunceford J, Hille D, Mauro D, Stein MN, Wang-Gillam A, Trull L, Lockhart AC.Invest New Drugs. 2016 Feb;34(1):84-95. doi: 10.1007/s10637-015-0306-7. Epub 2015 Dec 1. PMID: 26620496 Free PMC Article
2:Anticancer activity of the Aurora A kinase inhibitor MK-5108 in non-small-cell lung cancer (NSCLC) in vitro as monotherapy and in combination with chemotherapies. Chinn DC, Holland WS, Mack PC.J Cancer Res Clin Oncol. 2014 Jul;140(7):1137-49. doi: 10.1007/s00432-014-1675-6. Epub 2014 Apr 23. PMID: 24756365 Free PMC Article
3:MK-5108, a highly selective Aurora-A kinase inhibitor, shows antitumor activity alone and in combination with docetaxel. Shimomura T, Hasako S, Nakatsuru Y, Mita T, Ichikawa K, Kodera T, Sakai T, Nambu T, Miyamoto M, Takahashi I, Miki S, Kawanishi N, Ohkubo M, Kotani H, Iwasawa Y.Mol Cancer Ther. 2010 Jan;9(1):157-66. doi: 10.1158/1535-7163.MCT-09-0609. Epub 2010 Jan 6. PMID: 20053775 Free Article

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