BAY 1217389

Catalog No.S8215 Batch:S821501

Technical Data

Formula	C₂₇H₂₄F₅N₅O₃
Molecular Weight	561.50	CAS No.	1554458-53-5
Solubility (25°C)*	In vitro	DMSO	100 mg/mL (178.09 mM)
		Ethanol	8 mg/mL (14.24 mM)
		Water	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description

BAY 1217389 is an orally bioavailable, selective inhibitor of the serine/threonine kinase monopolar spindle 1 (Mps1) with IC50 values below 10 nmol/L while showing an excellent selectivity profile.

Targets

Mps1 ^[1]
(Cell-free assay)

0.63 nM

In vitro

In biochemical assays, the IC50 value of BAY 1217389 is 0.63±0.27 nmol/L. It shows high selectivity against other kinases and found to bind to PDGFRβ (<10 nmol/L), Kit (between 10 and 100 nmol/L), CLK1, CLK2, CLK4, JNK1, JNK2, JNK3, LATS1, MAK, MAPKAP2, MERTK, p38β, PDGFRα, PIP5K1C, PRKD1, and RPS6KA5 (between 100 and 1,000 nmol/L). In cellular mechanistic assays, BAY1217389 abrogats nocodazole-induced SAC activity and induced premature exit from mitosis ("mitotic breakthrough"), resulting in multinuclearity and tumor cell death. It is found to inhibit cell proliferation with a median IC50 of 6.7 nmol/L (range 3 to >300 nmol/L)^[1].

In vivo

In vivo, BAY 1217389 achieves moderate efficacy in monotherapy in tumor xenograft studies. Its blood clearance is found to be low in the tested species. Vss is high and terminal half-lives were long. BAY 1217389 is administered orally to female NMRI mouse (1 mg/kg) and male Wistar rat (0.5 mg/kg). Peak plasma concentrations are observed between 1.5 and 7 hours. Oral bioavailability is high in rat and moderate in mouse^[1].

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines Tumor cell lines HeLa-MaTu and HeLa-MaTu-ADR cells Concentrations -- Incubation Time 96 h Method Cells are seeded into 96-well plates at densities ranging from 1,000 to 5,000 cells per well in the appropriate medium supplemented with 10% FCS. After 24 hours, cells are treated in quadruplicates with serial dilutions of compounds. After further 96 hours, adherent cells are fixed with glutaraldehyde and stained with crystal violet. IC50 values are calculated by means of a 4-parameter fit using the company's own software.
Animal Study:^{^[1]}	Animal Models Male Wistar rats and female CD1 or NMRI nu/nu mice Dosages 1, 2, 4, or 8 mg/kg (p.o) Administration i.v or p.o

Cell Assay:^{^[1]}

Cell lines
Tumor cell lines HeLa-MaTu and HeLa-MaTu-ADR cells
Concentrations
--
Incubation Time
96 h
Method
Cells are seeded into 96-well plates at densities ranging from 1,000 to 5,000 cells per well in the appropriate medium supplemented with 10% FCS. After 24 hours, cells are treated in quadruplicates with serial dilutions of compounds. After further 96 hours, adherent cells are fixed with glutaraldehyde and stained with crystal violet. IC50 values are calculated by means of a 4-parameter fit using the company's own software.

Animal Study:^{^[1]}

Animal Models
Male Wistar rats and female CD1 or NMRI nu/nu mice
Dosages
1, 2, 4, or 8 mg/kg (p.o)
Administration
i.v or p.o

References

[1] Wengner AM, et al. Mol Cancer Ther. 2016, 15(4):583-92.

Selleck's BAY 1217389 has been cited by 8 publications

CDC7 inhibition induces replication stress-mediated aneuploid cells with an inflammatory phenotype sensitizing tumors to immune checkpoint blockade [ Nat Commun, 2023, 10.1038/s41467-023-43274-3]	PubMed: 37980406
Loss of RanGAP1 drives chromosome instability and rapid tumorigenesis of osteosarcoma [ Dev Cell, 2023, 58(3):192-210.e11]	PubMed: 36696903
Chromosomal instability can favor macrophage-mediated immune response and induce a broad, vaccination-like anti-tumor IgG response [ bioRxiv, 2023, 2023.04.02.535275]	PubMed: 37066426
MPS1 inhibition primes immunogenicity of KRAS-LKB1 mutant lung cancer [ Cancer Cell, 2022, 40(10):1128-1144.e8]	PubMed: 36150391
TTK Protein Kinase promotes temozolomide resistance through inducing autophagy in glioblastoma [ BMC Cancer, 2022, 22(1):786]	PubMed: 35850753
TTK inhibition increases cisplatin sensitivity in high-grade serous ovarian carcinoma through the mTOR/autophagy pathway [ Cell Death Dis, 2021, 12(12):1135]	PubMed: 34876569
Single-Chromosomal Gains Can Function as Metastasis Suppressors and Promoters in Colon Cancer. [ Dev Cell, 2020, 52(4):413-428]	PubMed: 32097652
Allele-selective lowering of mutant HTT protein by HTT-LC3 linker compounds [ Nature, 2019, 575(7781):203-209]	PubMed: 31666698

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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