Synonym
MK5108; MK-5108; MK 5108; VX689; VX 689; VX-689.
IUPAC/Chemical Name
(1r,4r)-4-(3-chloro-2-fluorophenoxy)-1-((6-(thiazol-2-ylamino)pyridin-2-yl)methyl)cyclohexane-1-carboxylic acid
InChi Key
LCVIRAZGMYMNNT-VVONHTQRSA-N
InChi Code
InChI=1S/C22H21ClFN3O3S/c23-16-4-2-5-17(19(16)24)30-15-7-9-22(10-8-15,20(28)29)13-14-3-1-6-18(26-14)27-21-25-11-12-31-21/h1-6,11-12,15H,7-10,13H2,(H,28,29)(H,25,26,27)/t15-,22-
SMILES Code
O=C([C@@]1(CC2=NC(NC3=NC=CS3)=CC=C2)CC[C@H](OC4=CC=CC(Cl)=C4F)CC1)O
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
soluble in DMSO, not soluble in water.
Shelf Life
>5 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
MK-5108 is a highly potent and specific inhibitor of Aurora A kinase with an IC50 value of 0.064 nM.
In vitro activity:
All cell lines demonstrated sustained growth inhibition following MK-5108 at varying nanomolar concentrations. MK-5108 induced G2/M accumulation, polyploidy, and apoptosis (increased sub-G1/PARP cleavage). Levels of Aurora A, TACC3, and Plk1 diminished.
Reference: J Cancer Res Clin Oncol. 2014 Jul;140(7):1137-49. https://pubmed.ncbi.nlm.nih.gov/24756365/
In vivo activity:
To examine whether MK-5108 can be used to impact the growth and metastasis of leiomyosarcoma in vivo, this study xeno-grafted athymic Fox1nu/nu mice (n = 3) with SK-LMS in a manner designed to mimic the intraperitoneal metastases that often characterize disease recurrences. Exposure to MK-5108 at both doses significantly decreased mean tumor implant size when compared with controls (Fig. 5B). Furthermore, this study found that MK-5108 resulted in decreased rates of proliferation (as indexed by Ki-67 expression), enhanced phospho-Histone H3 expression, and induced intratumoral apoptosis when formalin-fixed specimens of treated tumor xenografts were compared with controls (Fig. 5C–E).
Reference: Clin Cancer Res. 2012 Jun 15;18(12):3352-65. https://pubmed.ncbi.nlm.nih.gov/22535157/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMF |
5.0 |
10.82 |
| DMF:PBS (pH 7.2) (1:30) |
0.0 |
0.05 |
| DMSO |
35.5 |
76.85 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
461.94
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Chinn DC, Holland WS, Mack PC. 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. J Cancer Res Clin Oncol. 2014 Jul;140(7):1137-49. doi: 10.1007/s00432-014-1675-6. Epub 2014 Apr 23. PMID: 24756365; PMCID: PMC4565522.
2. Horwacik I, Durbas M, Boratyn E, Węgrzyn P, Rokita H. Targeting GD2 ganglioside and aurora A kinase as a dual strategy leading to cell death in cultures of human neuroblastoma cells. Cancer Lett. 2013 Dec 1;341(2):248-64. doi: 10.1016/j.canlet.2013.08.018. Epub 2013 Aug 17. PMID: 23962557.
3. Shan W, Akinfenwa PY, Savannah KB, Kolomeyevskaya N, Laucirica R, Thomas DG, Odunsi K, Creighton CJ, Lev DC, Anderson ML. A small-molecule inhibitor targeting the mitotic spindle checkpoint impairs the growth of uterine leiomyosarcoma. Clin Cancer Res. 2012 Jun 15;18(12):3352-65. doi: 10.1158/1078-0432.CCR-11-3058. Epub 2012 Apr 25. PMID: 22535157; PMCID: PMC5042205.
4. 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. MK-5108, a highly selective Aurora-A kinase inhibitor, shows antitumor activity alone and in combination with docetaxel. Mol Cancer Ther. 2010 Jan;9(1):157-66. doi: 10.1158/1535-7163.MCT-09-0609. Epub 2010 Jan 6. PMID: 20053775.
In vitro protocol:
1. Chinn DC, Holland WS, Mack PC. 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. J Cancer Res Clin Oncol. 2014 Jul;140(7):1137-49. doi: 10.1007/s00432-014-1675-6. Epub 2014 Apr 23. PMID: 24756365; PMCID: PMC4565522.
2. Horwacik I, Durbas M, Boratyn E, Węgrzyn P, Rokita H. Targeting GD2 ganglioside and aurora A kinase as a dual strategy leading to cell death in cultures of human neuroblastoma cells. Cancer Lett. 2013 Dec 1;341(2):248-64. doi: 10.1016/j.canlet.2013.08.018. Epub 2013 Aug 17. PMID: 23962557.
In vivo protocol:
1. Shan W, Akinfenwa PY, Savannah KB, Kolomeyevskaya N, Laucirica R, Thomas DG, Odunsi K, Creighton CJ, Lev DC, Anderson ML. A small-molecule inhibitor targeting the mitotic spindle checkpoint impairs the growth of uterine leiomyosarcoma. Clin Cancer Res. 2012 Jun 15;18(12):3352-65. doi: 10.1158/1078-0432.CCR-11-3058. Epub 2012 Apr 25. PMID: 22535157; PMCID: PMC5042205.
2. 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. MK-5108, a highly selective Aurora-A kinase inhibitor, shows antitumor activity alone and in combination with docetaxel. Mol Cancer Ther. 2010 Jan;9(1):157-66. doi: 10.1158/1535-7163.MCT-09-0609. Epub 2010 Jan 6. PMID: 20053775.
1: Shan W, Akinfenwa PY, Savannah KB, Kolomeyevskaya N, Laucirica R, Thomas DG, Odunsi K, Creighton CJ, Lev DC, Anderson ML. A small-molecule inhibitor targeting the mitotic spindle checkpoint impairs the growth of uterine leiomyosarcoma. Clin Cancer Res. 2012 Jun 15;18(12):3352-65. Epub 2012 Apr 25. PubMed PMID: 22535157.
2: Chefetz I, Holmberg JC, Alvero AB, Visintin I, Mor G. Inhibition of Aurora-A kinase induces cell cycle arrest in epithelial ovarian cancer stem cells by affecting NFĸB pathway. Cell Cycle. 2011 Jul 1;10(13):2206-14. Epub 2011 Jul 1. PubMed PMID: 21623171; PubMed Central PMCID: PMC3154367.
3: Kretzner L, Scuto A, Dino PM, Kowolik CM, Wu J, Ventura P, Jove R, Forman SJ, Yen Y, Kirschbaum MH. Combining histone deacetylase inhibitor vorinostat with aurora kinase inhibitors enhances lymphoma cell killing with repression of c-Myc, hTERT, and microRNA levels. Cancer Res. 2011 Jun 1;71(11):3912-20. Epub 2011 Apr 18. PubMed PMID: 21502403; PubMed Central PMCID: PMC3107377.
4: 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. MK-5108, a highly selective Aurora-A kinase inhibitor, shows antitumor activity alone and in combination with docetaxel. Mol Cancer Ther. 2010 Jan;9(1):157-66. Epub 2010 Jan 6. PubMed PMID: 20053775.
5: Lok W, Klein RQ, Saif MW. Aurora kinase inhibitors as anti-cancer therapy. Anticancer Drugs. 2010 Apr;21(4):339-50. Review. PubMed PMID: 20016367.
