2-[[2-Ethoxy-4-(4-hydroxy-1-piperidinyl)phenyl]amino]-5,11-dihydro-5,11-dimethyl-6H-pyrimido[4,5-b][1,4]benzodiazepin-6-one Chemical Properties

Boiling point:

741.8±70.0 °C(Predicted)

Density 

1.301

storage temp. 

Store at 4°C

solubility 

≥23.75 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH

form 

solid

pka

14.76±0.20(Predicted)

color 

Off-white to light yellow

Safety Information

HS Code 

2933599590

2-[[2-Ethoxy-4-(4-hydroxy-1-piperidinyl)phenyl]amino]-5,11-dihydro-5,11-dimethyl-6H-pyrimido[4,5-b][1,4]benzodiazepin-6-one Usage And Synthesis

Description

XMD8-92 is an ERK5 inhibitor (K_d = 80 nM) that less potently inhibits DCAMKL2, TNK1, and Plk4 (K_ds = 190, 890, and 600 nM, respectively) in a panel of 402 kinases. It blocks ERK5 autophosphorylation, ERK5-mediated phosphorylation of promyelocytic leukemia protein (PML), and PML-dependent activation of p21. XMD8-92 inhibits AP-1 transcriptional activity induced by MEK5-activated ERK5 but not that induced by Cdc37. It inhibits bFGF-induced angiogenesis in a Matrigel^™ plug assay in mice and reduces tumor growth in a HeLa mouse xenograft model when administered at a dose of 50 mg/kg twice per day. XMD8-92 also binds bromodomain-containing protein 4 (BRD4; K_d = 170 nM for BRD4 bromodomain 1).

Uses

XMD 8-92, is a BMK1 inhibitor and a highly selective inhibitor of ERK5 activity. XMD8-92 blocks cellular BMK1 activation and significantly suppresses tumor growth in lung and cervical tumor models and is well tolerated in animals.

Definition

ChEBI: XMD8-92 is a dimethylpyrimido[4,5-b][1,4]benzodiazepin-6-one carrying at C-2 on the pyrimidine ring a [2-ethoxy-4-(4-hydroxypiperidin-1-yl)phenyl]amino substituent. It is an inhibitor of the BMK1 kinase pathway. It has a role as a protein kinase inhibitor.

in vivo

IC 50

BMK1: 80 nM (Kd); BRD4: 190 nM (Kd)

storage

Store at RT

References

[1] QINGKAI YANG. Pharmacological inhibition of BMK1 suppresses tumor growth through promyelocytic leukemia protein.[J]. Cancer Cell, 2010: 258-267. DOI: 10.1016/j.ccr.2010.08.008
[2] TATIANA ERAZO. Canonical and kinase activity-independent mechanisms for extracellular signal-regulated kinase 5 (ERK5) nuclear translocation require dissociation of Hsp90 from the ERK5-Cdc37 complex.[J]. Molecular and Cellular Biology, 2013, 33 8: 1671-1686. DOI: 10.1128/mcb.01246-12
[3] E. C. LIN. ERK5 kinase activity is dispensable for cellular immune response and proliferation[J]. Proceedings of the National Academy of Sciences, 2016, 11 1: 11865-11870. DOI: 10.1073/pnas.1609019113

2-[[2-Ethoxy-4-(4-hydroxy-1-piperidinyl)phenyl]amino]-5,11-dihydro-5,11-dimethyl-6H-pyrimido[4,5-b][1,4]benzodiazepin-6-one(1234480-50-2)Related Product Information

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