Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C21H27NO6 |
Molecular Weight | 389.4422 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 4 / 4 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CCNC1=CC(O)=C2C(=C1)\C=C\C[C@H](O)[C@H](O)C(=O)C=C[C@@H](C)[C@H](C)OC2=O
InChI
InChIKey=MWUFVYLAWAXDHQ-HMNLTAHHSA-N
InChI=1S/C21H27NO6/c1-4-22-15-10-14-6-5-7-16(23)20(26)17(24)9-8-12(2)13(3)28-21(27)19(14)18(25)11-15/h5-6,8-13,16,20,22-23,25-26H,4,7H2,1-3H3/b6-5+,9-8-/t12-,13+,16+,20+/m1/s1
Molecular Formula | C21H27NO6 |
Molecular Weight | 389.4422 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 4 / 4 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
E-6201 and discovered that the compound inhibits lipopolysaccharide-activated TNF-alpha reporter activity in THP-1-33 cells and selectively inhibits mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK)-1 and MEK kinase-1 in cell-free biochemical assays. In addition, E-6201 showed inhibitory activity in several other cell-based systems: 1) phosphorylation of c-jun N-terminal kinase and p38 MAPKs; 2) nuclear factor-kappaB and activated protein-1 activation in various cell types; 3) interleukin (IL)-2 production from human lymphocytes; 4) hyperproliferation of human keratinocytes; 5) IL-8 production from human keratinocytes; and 6) proinflammatory cytokine production from human peripheral blood mononuclear cells. Based on this data, E-6201 may be beneficial for treatment of inflammatory and hyperproliferative diseases such as psoriasis through its anti-inflammatory activities on immune cells and anti-hyperproliferative activities on keratinocytes. E-6201 exhibits anti-tumor efficacy against TNBC in vitro and anti-metastasis efficacy against triple-negative breast cancer in vivo.
Approval Year
PubMed
Title | Date | PubMed |
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E6201 [(3S,4R,5Z,8S,9S,11E)-14-(ethylamino)-8, 9,16-trihydroxy-3,4-dimethyl-3,4,9,19-tetrahydro-1H-2-benzoxacyclotetradecine-1,7(8H)-dione], a novel kinase inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK)-1 and MEK kinase-1: in vitro characterization of its anti-inflammatory and antihyperproliferative activities. | 2009 Nov |
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Discovery of anti-inflammatory clinical candidate E6201, inspired from resorcylic lactone LL-Z1640-2, III. | 2010 May 15 |
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E6201, a novel kinase inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase-1 and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase-1: in vivo effects on cutaneous inflammatory responses by topical administration. | 2010 Oct |
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The Dual MEK/FLT3 Inhibitor E6201 Exerts Cytotoxic Activity against Acute Myeloid Leukemia Cells Harboring Resistance-Conferring FLT3 Mutations. | 2016 Mar 15 |
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Safety, pharmacokinetics, and preliminary efficacy of E6201 in patients with advanced solid tumours, including melanoma: results of a phase 1 study. | 2018 Jun |
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Brain Distribution of a Novel MEK Inhibitor E6201: Implications in the Treatment of Melanoma Brain Metastases. | 2018 May |
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E6201, an intravenous MEK1 inhibitor, achieves an exceptional response in BRAF V600E-mutated metastatic malignant melanoma with brain metastases. | 2019 Aug |
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Correction to: Anti-tumor and anti-metastasis efficacy of E6201, a MEK1 inhibitor, in preclinical models of triple-negative breast cancer. | 2019 Jul |
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Anti-tumor and anti-metastasis efficacy of E6201, a MEK1 inhibitor, in preclinical models of triple-negative breast cancer. | 2019 Jun |
Patents
Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 03:01:46 GMT 2023
by
admin
on
Sat Dec 16 03:01:46 GMT 2023
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Record UNII |
CZP9GB25HO
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Record Status |
Validated (UNII)
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Record Version |
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603987-35-5
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DB11687
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1108193-99-2
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CZP9GB25HO
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10172827
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CHEMBL1097999
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100000175304
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C79848
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