1228960-69-7

Basic information

• Product Name: MLN0905
• Synonyms: MLN0905;2-[[5-[3-(Dimethylamino)propyl]-2-methyl-3-pyridinyl]amino]-5,7-dihydro-9-(trifluoromethyl)- 6H-pyrimido[5,4-d][1]benzazepine-6-thione;PLK1 Inhibitor;6H-Pyrimido[5,4-d][1]benzazepine-6-thione, 2-[[5-[3-(dimethylamino)propyl]-2-methyl-3-pyridinyl]amino]-5,7-dihydro-9-(trifluoromethyl)-;2-[[5-[3-(Dimethylamino)propyl]-2-methyl-3-pyridinyl]amino]-5,7-dihydro-9-(trifluoromethyl)- 6H-pyrimido[5,4-d][1]benzazepine-6-thione MLN0905;MLN0905 2-[[5-[3-(Dimethylamino)propyl]-2-methyl-3-pyridinyl]amino]-5,7-dihydro-9-(trifluoromethyl)- 6H-pyrimido[5,4-d][1]benzazepine-6-thione
• CAS NO: 1228960-69-7
• Molecular Formula: C24H25F3N6S
• Molecular Weight: 486.5557096
• Product Categories: Inhibitors
• Mol File: 1228960-69-7.mol

Chemical Properties

• Appearance: /
• Density: 1.37±0.1 g/cm3 (20 ºC 760 Torr)
• Solubility: ≥24.35 mg/mL in DMSO
• CAS DataBase Reference: MLN0905(CAS DataBase Reference)
• NIST Chemistry Reference: MLN0905(1228960-69-7)
• EPA Substance Registry System: MLN0905(1228960-69-7)

Safety Data

• Hazardous Substances Data: 1228960-69-7(Hazardous Substances Data)

Usage

Biological Activity

mln0905 is a potent inhibitor of plk1 with ic50 value ranges from 3 to 24 nm [1].polo-like kinase 1 (plk1) is a family of conserved serine/threonine kinases and plays an important role in regulating cell cycle. it has been revealed that plk1 drives cell cycle progression by triggerting g2/m transition and is considered as a pro-oncogene which overexpressed in tumor cells [2].mln0905 is a selective plk1 inhibitor and has similar effect as rnai hnockdown. when tested with ht-29 cells, mln0905 treatment significantly increased phish3 expression which indicated that cells were arrested in g2/m phase by inhibiting plk1 expression [1].in mouse model with human diffuse large b-cell lymphoma (dlbcl) cell line ocily-19 subcutaneous xenograft, co-administration of mln0905 and rituximab markedly reduced tumor volume and increased survival time through inhibiting plk1 which resulted in mitotic arrest [1]. and the same result was achieved when using nude mice model with human colon tumor ht29 xenograft, mln0905 treatment significantly inhibited tumor growth or progression [3].

references

[1]. shi, j.q., et al., mln0905, a small-molecule plk1 inhibitor, induces antitumor responses in human models of diffuse large b-cell lymphoma. mol cancer ther, 2012. 11(9): p. 2045-53.[2]. espeut, j., et al., natural loss of mps1 kinase in nematodes uncovers a role for polo-like kinase 1 in spindle checkpoint initiation. cell rep, 2015. [3]. duffey, m.o., et al., discovery of a potent and orally bioavailable benzolactam-derived inhibitor of polo-like kinase 1 (mln0905). j med chem, 2012. 55(1): p. 197-208.

Upstream product

• 1228962-19-3 MLN₀₉₀₅ 
• 1228961-00-9 9-trifluoromethyl-2-({5-[3-(dimethylamino)propyl]-2-methylpyridin-3-yl}amino)-5,7-dihydro-6H-pyrimido[5,4-d][1]benzazepin-6-one 
• 61500-87-6 methyl 2-Amino-4-(trifluoromethyl)benzoate 
• 1228960-84-6 methyl 2,5-dioxo-8-(trifluoromethyl)-2,3,4,5-tetrahydro-1H-benzo[b]azepine-4-carboxylate 
• 1228960-83-5 methyl 2-(4-methoxy-4-oxobutanamido)-4-(trifluoromethyl)benzoate 
• 1228960-85-7 8-trifluoromethyl-3,4-dihydro-1H-1-benzazepine-2,5-dione 
• 1228997-60-1 C₁₂H₂₁N₅ 
• 1228960-93-7 8-trifluoromethyl-4-((dimethylamino)methylene)-3,4-dihydro-1H-benzo[b]azepine-2,5-dione 
• 1351438-89-5 di-tert-butyl [(Z)-({5-[3-(dimethylamino)propyl]-2-methylpyridin-3-yl}amino)methylylidene]biscarbamate 

Relevant articles and documents

Discovery of a potent and orally bioavailable benzolactam-derived inhibitor of polo-like kinase 1 (MLN0905)

This article describes the discovery of a series of potent inhibitors of Polo-like kinase 1 (PLK1). Optimization of this benzolactam-derived chemical series produced an orally bioavailable inhibitor of PLK1 (12c, MLN0905). In vivo pharmacokinetic-pharmacodynamic experiments demonstrated prolonged mitotic arrest after oral administration of 12c to tumor bearing nude mice. A subsequent efficacy study in nude mice achieved tumor growth inhibition or regression in a human colon tumor (HT29) xenograft model.

5, 7-DIHYDRO- 6H-PYRIMIDO [ 5, 4-D] [ 1 ] BENZAZEPIN-6-THIONES AS PLK INHIBITORS

This invention provides compounds of formula I: wherein R1, R2, R3, R4, R5, and R6 are as described in the specification. The compounds are inhibitors of PLK and are thus useful for treating proliferative, inflammatory, or cardiovascular disorders.