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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
Structure of E-6201

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

HIDE SMILES / InChI

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

PubMed

TitleDatePubMed
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
Discovery of anti-inflammatory clinical candidate E6201, inspired from resorcylic lactone LL-Z1640-2, III.
2010 May 15
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
The Dual MEK/FLT3 Inhibitor E6201 Exerts Cytotoxic Activity against Acute Myeloid Leukemia Cells Harboring Resistance-Conferring FLT3 Mutations.
2016 Mar 15
Safety, pharmacokinetics, and preliminary efficacy of E6201 in patients with advanced solid tumours, including melanoma: results of a phase 1 study.
2018 Jun
Brain Distribution of a Novel MEK Inhibitor E6201: Implications in the Treatment of Melanoma Brain Metastases.
2018 May
E6201, an intravenous MEK1 inhibitor, achieves an exceptional response in BRAF V600E-mutated metastatic malignant melanoma with brain metastases.
2019 Aug
Correction to: Anti-tumor and anti-metastasis efficacy of E6201, a MEK1 inhibitor, in preclinical models of triple-negative breast cancer.
2019 Jul
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 Sat Dec 16 03:01:46 GMT 2023
Edited
by admin
on Sat Dec 16 03:01:46 GMT 2023
Record UNII
CZP9GB25HO
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
E-6201
Common Name English
E6201
Code English
ER-806201
Code English
1H-2-BENZOXACYCLOTETRADECIN-1,7(8H)-DIONE, 14-(ETHYLAMINO)-3,4,9,10-TETRAHYDRO-8,9,16-TRIHYDROXY-3,4-DIMETHYL-, (3S,4R,5Z,8S,9S,11E)-
Systematic Name English
Code System Code Type Description
CAS
603987-35-5
Created by admin on Sat Dec 16 03:01:46 GMT 2023 , Edited by admin on Sat Dec 16 03:01:46 GMT 2023
PRIMARY
DRUG BANK
DB11687
Created by admin on Sat Dec 16 03:01:46 GMT 2023 , Edited by admin on Sat Dec 16 03:01:46 GMT 2023
PRIMARY
CAS
1108193-99-2
Created by admin on Sat Dec 16 03:01:46 GMT 2023 , Edited by admin on Sat Dec 16 03:01:46 GMT 2023
NON-SPECIFIC STEREOCHEMISTRY
FDA UNII
CZP9GB25HO
Created by admin on Sat Dec 16 03:01:46 GMT 2023 , Edited by admin on Sat Dec 16 03:01:46 GMT 2023
PRIMARY
PUBCHEM
10172827
Created by admin on Sat Dec 16 03:01:46 GMT 2023 , Edited by admin on Sat Dec 16 03:01:46 GMT 2023
PRIMARY
ChEMBL
CHEMBL1097999
Created by admin on Sat Dec 16 03:01:46 GMT 2023 , Edited by admin on Sat Dec 16 03:01:46 GMT 2023
PRIMARY
SMS_ID
100000175304
Created by admin on Sat Dec 16 03:01:46 GMT 2023 , Edited by admin on Sat Dec 16 03:01:46 GMT 2023
PRIMARY
NCI_THESAURUS
C79848
Created by admin on Sat Dec 16 03:01:46 GMT 2023 , Edited by admin on Sat Dec 16 03:01:46 GMT 2023
PRIMARY
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ACTIVE MOIETY