| Identification | More | [Name]
XMD8-92 | [CAS]
1234480-50-2 | [Synonyms]
XMD 8-92
XMD 8-92 (free base)
2-((2-ethoxy-4-(4-hydroxypiperidin-1-yl)phenyl)amino)-5,11-dimethyl-5H-benzo[e]pyrimido[5,4-b][1,4]diazepin-6(11H)-one
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
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 XMD 8-92
XMD 8-92 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 | [Molecular Formula]
C26H30N6O3 | [MDL Number]
MFCD18782742 | [MOL File]
1234480-50-2.mol | [Molecular Weight]
475 |
| Chemical Properties | Back Directory | [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 | [InChIKey]
QAPAJIZPZGWAND-UHFFFAOYSA-N | [SMILES]
OC(CC1)CCN1C2=CC=C(NC3=NC(N(C)C(C=CC=C4)=C4C(N5C)=O)=C5C=N3)C(OCC)=C2 |
| Hazard Information | Back Directory | [Description]
XMD8-92 is an ERK5 inhibitor (Kd = 80 nM) that less potently inhibits DCAMKL2, TNK1, and Plk4 (Kds = 190, 890, and 600 nM, respectively) in a panel of 402 kinases.1 It blocks ERK5 autophosphorylation, ERK5-mediated phosphorylation of promyelocytic leukemia protein (PML), and PML-dependent activation of p21.1 XMD8-92 inhibits AP-1 transcriptional activity induced by MEK5-activated ERK5 but not that induced by Cdc37.2 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.1 XMD8-92 also binds bromodomain-containing protein 4 (BRD4; Kd = 170 nM for BRD4 bromodomain 1).3 | [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]
XMD8-92 (i.p.; twice a day for 28 days) significantly inhibits the growth of the xenografted human tumors[1]. | Animal Model: | HeLa Xenograft Model (6-week-old Nod/Scid mice)[1] | | Dosage: | 50 mg/kg | | Administration: | I.p.; twice a day for 28 days | | Result: | Significantly inhibited the growth of the xenografted human tumors.
|
| [IC 50]
BMK1: 80 nM (Kd); BRD4: 190 nM (Kd) | [storage]
Store at 4°C | [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 |
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| Company Name: |
Moltt Biocem Co., Ltd.
|
| Telephone: |
+86-21-38682181 15900741819 |
| Website: |
www.chemicalbook.com/ShowSupplierProductsList15856/0_EN.htm |
| Company Name: |
LETOPHARM LIMITED
|
| Telephone: |
+86-21-5821 5861 |
| Website: |
www.letopharm.com |
| Company Name: |
D&C Chemicals
|
| Telephone: |
+86-21-58447131 |
| Website: |
www.chemicalbook.com/ShowSupplierProductsList16963/0_EN.htm |
|