| Identification | Back Directory | [Name]
MLN0905 | [CAS]
1228960-69-7 | [Synonyms]
MLN0905
CS-1458
AI314412
AI3-14412
AI3 14412
PLK1 Inhibitor
MLN0905 USP/EP/BP
PLK1 INHIBITOR; MLN 0905; MLN-0905
2-[[5-[3-(Dimethylamino)propyl]-2-methyl-3-pyridinyl]amino]-5,7-dihydro-9-(trifluoromethyl)- 6H-pyrimido[5,4-d][1]benzazepine-6-thione
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 | [Molecular Formula]
C24H25F3N6S | [MDL Number]
MFCD22683863 | [MOL File]
1228960-69-7.mol | [Molecular Weight]
486.56 |
| Chemical Properties | Back Directory | [Boiling point ]
624.4±65.0 °C(Predicted) | [density ]
1.37±0.1 g/cm3 (20 ºC 760 Torr) | [storage temp. ]
Store at -20°C | [solubility ]
≥24.35 mg/mL in DMSO | [form ]
solid | [pka]
9.80±0.20(Predicted) | [color ]
Off-white to yellow |
| Hazard Information | Back Directory | [Uses]
MLN0905 is a potent, orally active Polo-like kinase 1 (PLK1) inhibitor. MLN0905 has inhibitory potency against PLK1 with an IC50 value of 2 nM. MLN0905 can be used for the research of cancer[1][2]. | [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]. | [in vivo]
MLN0905 (p.o.; 50 mg/kg) shows a high sustained PD response in nude mice HT29 xenograft tumors[1].
MLN0905 (p.o.; 6.25, 12.5, 25, 50 mg/kg) exhibits significant antitumor activities in mice HT29 xenograft tumors[1].
MLN0905 (p.o.; 0-14.5 mg/kg; daily, QD×3/week) has marked antitumor effects in kinds of lymphoma xenograft model[1][2]. | Animal Model: | Tumor (HT29) xenograft model[1] | | Dosage: | 0-50 mg/kg | | Administration: | P.O; daily, QD×3/week | | Result: | Observed antitumor activity, tumor stasis or regression and well-tolerated oral doses. |
| [target]
PLK1 | [IC 50]
PLK1: 2 nM (IC50) | [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. |
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