1849590-01-7

1849590-01-7 structure

Name: eFT508
Chemical Name: 6'-[(6-Amino-4-pyrimidinyl)amino]-8'-methyl-2'H-spiro[cyclohexane-1,3'-imidazo[1,5-a]pyridine]-1',5'-dione
CAS Number: 1849590-01-7
Molecular Formula: C₁₇H₂₀N₆O₂
Molecular Weight: 340.380
Catalog: Signaling Pathways MAPK/ERK Pathway MNK
Create Date: 2018-05-06 04:41:24
Modify Date: 2024-01-06 18:04:26
eFT508 is a potent, highly selective, and orally bioavailable MNK1 and MNK2 inhibitor, with IC50s of 1-2 nM against both isoforms.

Name	6'-[(6-Amino-4-pyrimidinyl)amino]-8'-methyl-2'H-spiro[cyclohexane-1,3'-imidazo[1,5-a]pyridine]-1',5'-dione
Synonyms	Spiro[cyclohexane-1,3'(2'H)-imidazo[1,5-a]pyridine]-1',5'-dione, 6'-[(6-amino-4-pyrimidinyl)amino]-8'-methyl- 6'-[(6-Amino-4-pyrimidinyl)amino]-8'-methyl-2'H-spiro[cyclohexane-1,3'-imidazo[1,5-a]pyridine]-1',5'-dione eFT508

Description	eFT508 is a potent, highly selective, and orally bioavailable MNK1 and MNK2 inhibitor, with IC50s of 1-2 nM against both isoforms.
Related Catalog	Signaling Pathways >> MAPK/ERK Pathway >> MNK Research Areas >> Cancer
Target	MNK1:1-2 nM (IC50) MNK2:1-2 nM (IC50)
In Vitro	eFT508 reduces eIF4E phosphorylation dose-dependently at serine 209 (IC50=2-16 nM) in tumor cell lines. In a panel of appr 50 hematological cancers, eFT508 shows anti-proliferative activity against multiple DLBCL cell lines. Sensitivity to eFT508 in TMD8, OCI-Ly3 and HBL1 DLBCL cell lines is associated with dose-dependent decreases in production of pro-inflammatory cytokines including TNFα, IL-6, IL-10 and CXCL10. Further evaluation eFT508 mechanism of action demonstrates that decreased TNFα production correlates with a 2-fold decrease in TNFα mRNA half-life[1].
In Vivo	eFT508 shows significant anti-tumor activity in the TMD8 and HBL-1 ABC-DLBCL models, both of which harbor activating MyD88 mutations. Besides, eFT508 combines effectively with components of R-CHOP and with novel targeted agents, including ibrutinib and venetoclax, in human lymphoma models[1].
References	[1]. Kevin R. Webster, et al. eFT508, a Potent and Selective Mitogen-Activated Protein Kinase Interacting Kinase (MNK) 1 and 2 Inhibitor, Is Efficacious in Preclinical Models of Diffuse Large B-Cell Lymphoma (DLBCL). Blood 2015 126:1554;