MK-5198 - CAS 1010085-13-8
Catalog number: 1010085-13-8
Category: Inhibitor
Please be kindly noted products are not for therapeutic use. We do not sell to patients.
Molecular Formula:
C22H21ClFN3O3S
Molecular Weight:
461.94
COA:
Inquire
Targets:
Aurora Kinase
Description:
MK-5108 is a novel small molecule with potent inhibitory activity against Aurora-A kinase. Although most of the Aurora-kinase inhibitors target both Aurora-A and Aurora-B, MK-5108 specifically inhibited Aurora-A kinase in a panel of protein kinase assays. Inhibition of Aurora-A by MK-5108 in cultured cells induced cell cycle arrest at the G(2)-M phase in flow cytometry analysis. The effect was confirmed by the accumulation of cells with expression of phosphorylated Histone H3 and inhibition of Aurora-A autophosphorylation by immunostaining assays. MK-5108 also induced phosphorylated Histone H3 in skin and xenograft tumor tissues in a nude rat xenograft model. MK-5108 inhibited growth of human tumor cell lines in culture and in different xenograft models. Furthermore, the combination of MK-5108 and docetaxel showed enhanced antitumor activities compared with control and docetaxel alone-treated animals without exacerbating the adverse effects of docetaxel. MK-5108 is currently tested in clinical trials and offers a new therapeutic approach to combat human cancers as a single agent or in combination with existing taxane therapies.
Purity:
>98%
Appearance:
White to off-white solid
Synonyms:
MK5108; MK-5108; MK 5108; VX689; VX 689; VX-689.
MSDS:
Inquire
InChIKey:
LCVIRAZGMYMNNT-UHFFFAOYSA-N
InChI:
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)
Canonical SMILES:
C1CC(CCC1OC2=C(C(=CC=C2)Cl)F)(CC3=NC(=CC=C3)NC4=NC=CS4)C(=O)O
Current Developer:
Merck.
1.Fluorescent photoaffinity probes for mitotic protein kinase Aurora A.
Lavogina D;Kisand K;Raidaru G;Uri A Bioorg Med Chem Lett. 2015 Aug 15;25(16):3290-4. doi: 10.1016/j.bmcl.2015.05.060. Epub 2015 May 30.
We combined the advantages of the selective inhibitor VX689, the bisubstrate-analogue conjugate approach, and photoreactive amino acids to develop 8 photoaffinity probes for Aurora A. The most efficient compounds possessed one-digit nanomolar KD values in the equilibrium binding assay, inhibited Aurora A at elevated concentrations of ATP in the phosphorylation assay in the presence of TPX2, and formed covalent complexes with the recombinant kinase or Aurora A in HeLa cells upon UV-irradiation. The recognition of the correct target by the probes during formation of the covalent complex in the biochemical assay and in situ was demonstrated by competition experiments using the non-labelled inhibitors VX689 and MLN8237.
2.Co-inhibition of polo-like kinase 1 and Aurora kinases promotes mitotic catastrophe.
Li J;Hong MJ;Chow JP;Man WY;Mak JP;Ma HT;Poon RY Oncotarget. 2015 Apr 20;6(11):9327-40.
Mitosis is choreographed by a number of protein kinases including polo-like kinases and Aurora kinases. As these kinases are frequently dysregulated in cancers, small-molecule inhibitors have been developed for targeted anticancer therapies. Given that PLK1 and Aurora kinases possess both unique functions as well as co-regulate multiple mitotic events, whether pharmacological inhibition of these kinases together can enhance mitotic catastrophe remains an outstanding issue to be determined. Using concentrations of inhibitors that did not induce severe mitotic defects on their own, we found that both the metaphase arrest and mitotic slippage induced by inhibitors targeting Aurora A and Aurora B (MK-5108 and Barasertib respectively) were enhanced by a PLK1 inhibitor (BI 2536). We found that PLK1 is overexpressed in cells from nasopharyngeal carcinoma, a highly invasive cancer with poor prognosis, in comparison to normal nasopharyngeal epithelial cells. Nasopharyngeal carcinoma cells were more sensitive to BI 2536 as a single agent and co-inhibition with Aurora kinases than normal cells. These observations underscore the mechanism and potential benefits of targeting PLK1 and Aurora kinases to induce mitotic catastrophe in cancer cells.
3.Preclinical evaluation of the Aurora kinase inhibitors AMG 900, AZD1152-HQPA, and MK-5108 on SW-872 and 93T449 human liposarcoma cells.
Noronha S;Alt LAC;Scimeca TE;Zarou O;Obrzut J;Zanotti B;Hayward EA;Pillai A;Mathur S;Rojas J;Salamah R;Chandar N;Fay MJ In Vitro Cell Dev Biol Anim. 2018 Jan;54(1):71-84. doi: 10.1007/s11626-017-0208-4. Epub 2017 Dec 1.
Liposarcoma is a malignant soft tissue tumor that originates from adipose tissue and is one of the most frequently diagnosed soft tissue sarcomas in humans. There is great interest in identifying novel chemotherapeutic options for treating liposarcoma based upon molecular alterations in the cancer cells. The Aurora kinases have been identified as promising chemotherapeutic targets based on their altered expression in many human cancers and cellular roles in mitosis and cytokinesis. In this study, we investigated the effects of an Aurora kinase A inhibitor (MK-5108), an Aurora kinase B inhibitor (AZD1152-HQPA), and a pan-Aurora kinase inhibitor (AMG 900) on undifferentiated SW-872 and well-differentiated 93T449 human liposarcoma cells. Treatment of the SW-872 and 93T449 cells with MK-5108 (0-1000 nM), AZD1152-HQPA (0-1000 nM), and AMG 900 (0-1000 nM) for 72 h resulted in a dose-dependent decrease in the total viable cell number. Based upon the EC;50; values, the potency of the three Aurora kinase inhibitors in the SW-872 cells was as follows: AMG 900 (EC;50; = 3.7 nM) > AZD1152-HQPA (EC;50; = 43.4 nM) > MK-5108 (EC;50; = 309.0 nM), while the potency in the 93T449 cells was as follows: AMG 900 (EC;50; = 6.
Molecular Weight Calculator Molarity Calculator Solution Dilution Calculator

Related Aurora Kinase Products


CAS 1146618-41-8 SNS-314 Mesylate

SNS-314 Mesylate
(CAS: 1146618-41-8)

SNS-314 Mesylate is a potent and selective inhibitor of Aurora A, Aurora B and Aurora C with IC50 of 9 nM, 31 nM, and 3 nM, respectively. It is less potent to T...

CAS 942918-07-2 GSK-1070916A

GSK-1070916A
(CAS: 942918-07-2)

GSK-1070916A is an ATP-competitive inhibitor of the serine/threonine kinases Aurora B and C with potential antineoplastic activity. Aurora B/C kinase inhibitor ...

CAS 942947-93-5 CCT129202

CCT129202
(CAS: 942947-93-5)

CCT129202 is an inhibitor of Aurora kinase activity and displays a favorable antineoplastic effect in preclinical studies. CCT129202 significantly reversed ABCB...

CAS 945595-80-2 AMG-900

AMG-900
(CAS: 945595-80-2)

AMG 900 is a small-molecule inhibitor of Aurora kinases A, B and C with potential antineoplastic activity. Aurora kinase inhibitor AMG 900 selectively binds to ...

CAS 885325-71-3 MK-8745

MK-8745
(CAS: 885325-71-3)

MK-8745 is a novel Aurora-A specific inhibitor. MK8745 induced apoptotic cell death in a p53-dependent manner when tested in vitro in cell lines of multiple lin...

CAS 693228-63-6 CYC116

CYC116
(CAS: 693228-63-6)

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 ...

CAS 934541-31-8 TAK-901

TAK-901
(CAS: 934541-31-8)

TAK-901 is a small-molecule inhibitor of the serine-threonine kinase Aurora B with potential antineoplastic activity. Aurora B kinase inhibitor TAK-901 binds to...

CAS 869363-13-3 MLN8054

MLN8054
(CAS: 869363-13-3)

MLN8054 is an aurora kinase inhibitor MLN8054, which is an orally bioavailable, highly selective small molecule inhibitor of the serine/threonine protein kinase...

Chemical Structure

CAS 1010085-13-8 MK-5198

Quick Inquiry

Verification code

Featured Items