Mps1

MPS1 (monopolar spindle) protein kinases are found widely, but not ubiquitously, in eukaryotes. This family of potentially dual-specific protein kinases is among several that regulate a number of steps of mitosis. The most widely conserved MPS1 kinase functions involve activities at the kinetochore in both the chromosome attachment and the spindle checkpoint. MPS1 kinases also function at centrosomes. Beyond mitosis, MPS1 kinases have been implicated in development, cytokinesis, and several different signaling pathways.

1124329-14-1
AZ 3146
1124329-14-1
1125593-20-5
Mps1-IN-1
1125593-20-5
1202055-32-0
NMS-P715
1202055-32-0
1202055-34-2
NMS-P715
1202055-34-2
TC Mps1 12
1206170-62-8
1228817-38-6
Mps1-IN-2
1228817-38-6
Mps BAY 2a
1382477-96-4
1443763-60-7
Mps1-IN-5
1443763-60-7
1609584-72-6
Mps1-IN-3
1609584-72-6

Background


An overview of MPS1

The monopolar spindle 1 (MPS1) protein kinases, also known as TTK in mammals, were first found in budding yeast. MPS1 is a dual-specific protein kinase widely present in eukaryotes, which can phosphorylate tyrosine or serine/threonine residues and exert function in mitosis and several different signaling pathways. A mutation in the MPS1 gene would result in monopolar spindle since the involvement in the activities at the kinetochore in both the chromosome attachment and the spindle checkpoint. The spindle assembly checkpoint ensures all the chromosomes are arranged on the mitotic board, and its function defect will lead to chromosome instability and aneuploidy, which is a common feature of many tumor cells.

Inhibition of MPS1

Experiments have suggested that inhibition of MPS1 protein kinase activity or reduction of MPS1 protein level through siRNA could lead to spindle assembly checkpoint dysfunction and tumor cell death. Therefore, it is very attractive to explore anti-tumor drugs targeting MPS1. It is reported that MPS1 inhibitors were able to effectively kill tumor cells in tumor cell culture. The first small molecular MPS1 inhibitor is cincreasin, with a weak inhibitory effect. Subsequently, there are an increasing number of MPS1 inhibitors described by scientists, such as MPS1-IN-1, SP600125, Reversine, 3MB-PP1, 23-dMB-PP1 and more on. Among these inhibitors, Reversine is the most attractive compound inhibitor. Researchers discovered that the addition of 3 nmol /L of Reversine resulted in 50% tumor cell death.

MPS1 and diseases

The high expression of MSP1 exists in many human tumors, like breast cancer, gastric cancer tissue, and lung cancer. For example, a recent study reported that MPS1 was highly expressed in breast cancer, and the degradation of MPS1 would lead to the death of breast cancer cells. This fact suggests that the design of small molecular compounds or peptides that specifically induce degradation of MPS1 will provide new ideas for the development of anti-tumor drugs targeting MPS1.

References:

1. Liu, X., & Winey, M. (2012). The MPS1 family of protein kinases. Annual review of biochemistry, 81, 561-585.

2. Fisk, H. A., & Winey, M. (2004). Spindle regulation: Mps1 flies into new areas. Current biology, 14(24), R1058-R1060.

3. de Castro, I. P., de C├írcer, G., Montoya, G., & Malumbres, M. (2008). Emerging cancer therapeutic opportunities by inhibiting mitotic kinases. Current opinion in pharmacology, 8(4), 375-383.