SCH772984   Click here for help

GtoPdb Ligand ID: 8056

Synonyms: SCH-772984
PDB Ligand
Compound class: Synthetic organic
Comment: SCH772984 is an experimental inhibitor of the mitogen-activated protein kinases ERK1 and ERK2 [2]. The in vitro mechanism of action of SCH772984 is notable, in that it inhibits both the catalytic activity of ERK1/2 and also inhibits phosphorylation of ERK1/2. This is in contrast to other ERK inhibitors that target the ATP-binding site and thus inhibit only the catalytic activity of the kinases. The dual action of compounds like SCH772984 is predicted to block the nuclear localization of pERK and more completely suppress MAPK pathway signaling [2]. This type of inhibitor may provide improved clinical efficacy, particularly in relation to the emergence of acquired resistance that occurs in BRAF and MEK inhibitor-treated cancers. Unfortunately, SCH772984 is not active in vivo (oral or intraperitoneal administration results in poor exposure levels) [1].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 10
Hydrogen bond donors 2
Rotatable bonds 9
Topological polar surface area 123.24
Molecular weight 587.28
XLogP 2.69
No. Lipinski's rules broken 0
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Canonical SMILES O=C(N1CCN(CC1)c1ccc(cc1)c1ncccn1)CN1CCC(C1)C(=O)Nc1ccc2c(c1)c(n[nH]2)c1ccncc1
Isomeric SMILES O=C(N1CCN(CC1)c1ccc(cc1)c1ncccn1)CN1CC[C@H](C1)C(=O)Nc1ccc2c(c1)c(n[nH]2)c1ccncc1
InChI InChI=1S/C33H33N9O2/c43-30(42-18-16-41(17-19-42)27-5-2-24(3-6-27)32-35-11-1-12-36-32)22-40-15-10-25(21-40)33(44)37-26-4-7-29-28(20-26)31(39-38-29)23-8-13-34-14-9-23/h1-9,11-14,20,25H,10,15-19,21-22H2,(H,37,44)(H,38,39)/t25-/m1/s1
Selectivity at enzymes
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
mitogen-activated protein kinase 1 Primary target of this compound Hs Inhibitor Inhibition 8.4 – 9.0 pIC50 - 2
pIC50 9.0 (IC50 1x10-9 M) [2]
pIC50 8.4 (IC50 4x10-9 M) [2]