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Details

Stereochemistry ABSOLUTE
Molecular Formula C21H22Cl2N4O2
Molecular Weight 433.3316
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ULIXERTINIB

SMILES

CC(C)Nc1cc(-c2cc(C(=O)N[C@]([H])(CO)c3cccc(c3)Cl)[nH]c2)c(cn1)Cl

InChI

InChIKey=KSERXGMCDHOLSS-LJQANCHMSA-N
InChI=1S/C21H22Cl2N4O2/c1-12(2)26-20-8-16(17(23)10-25-20)14-7-18(24-9-14)21(29)27-19(11-28)13-4-3-5-15(22)6-13/h3-10,12,19,24,28H,11H2,1-2H3,(H,25,26)(H,27,29)/t19-/m1/s1

HIDE SMILES / InChI

Molecular Formula C21H22Cl2N4O2
Molecular Weight 433.3316
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment:: http://cancerres.aacrjournals.org/content/75/15_Supplement/4693 |https://biomed-valley.com/portfolio/bvd-523

BVD-523 potently and selectively inhibits ERK1 and ERK2 kinases in a reversible, ATP-competitive fashion. Consistent with its mechanism of action, BVD-523 inhibits signal transduction, cell proliferation, and cell survival, most potently in cell lines bearing mutations that activate MAPK pathway signaling. Similarly, single-agent BVD-523 inhibits tumor growth in vivo in BRAF-mutant melanoma and colorectal xenografts as well as in KRAS-mutant colorectal and pancreatic models. BioMed Valley Discoveries is developing ulixertinib, a potent and selective small molecule inhibitor of ERK 1 and 2 kinases, as an oral treatment for cancers harbouring mutations in the MAPK signaling pathway. Phase I/II development of the drug for advanced cancers including, acute myeloid leukaemia and myelodysplastic syndromes is underway in the US. A phase I trial is underway in the US for pancreatic cancer.

Approval Year

PubMed

PubMed

TitleDatePubMed
Structure-Guided Design of Highly Selective and Potent Covalent Inhibitors of ERK1/2.
2015 Jun 11
Determination of ulixertinib in mice plasma by LC-MS/MS and its application to a pharmacokinetic study in mice.
2016 Jun 5
Patents

Sample Use Guides

In March 2016, BioMed Valley Discoveries, in collaboration with Washington University School of Medicine, initiated a phase Ib trial to evaluate the safety and efficacy of ulixertinib 600 mg bid at the RP2D in combination with nab-paclitaxel 125 mg/m2 plus gemcitabine 1000 mg/m2 in patients with newly diagnosed metastatic pancreatic cancer (15-x384; NCT02608229)
Route of Administration: Oral
In Vitro Use Guide
Curator's Comment:: retrieved from http://www.selleckchem.com/products/ulixertinib-bvd-523-vrt752271.html
In an A375 melanoma cell line containing a b-RAFV600E mutation, Ulixertinib reduces the levels of phosphorylated ERK2 (pERK) and of the phosphorylation of the downstream kinase RSK (pRSK) with IC50 of 4.1/0.14 μM, respectively. Ulixertinib also inhibits A375 cell proliferation with IC50 of 180 nM.
Substance Class Chemical
Created
by admin
on Sat Jun 26 09:24:56 UTC 2021
Edited
by admin
on Sat Jun 26 09:24:56 UTC 2021
Record UNII
16ZDH50O1U
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ULIXERTINIB
INN   WHO-DD  
INN  
Official Name English
BVD-ERK
Code English
1H-PYRROLE-2-CARBOXAMIDE, 4-(5-CHLORO-2-((1-METHYLETHYL)AMINO)-4-PYRIDINYL)-N-((1S)-1-(3-CHLOROPHENYL)-2-HYDROXYETHYL)-
Systematic Name English
ULIXERTINIB [INN]
Common Name English
ULIXERTINIB [WHO-DD]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C129825
Created by admin on Sat Jun 26 09:24:56 UTC 2021 , Edited by admin on Sat Jun 26 09:24:56 UTC 2021
NCI_THESAURUS C61074
Created by admin on Sat Jun 26 09:24:56 UTC 2021 , Edited by admin on Sat Jun 26 09:24:56 UTC 2021
Code System Code Type Description
NCI_THESAURUS
C104744
Created by admin on Sat Jun 26 09:24:56 UTC 2021 , Edited by admin on Sat Jun 26 09:24:56 UTC 2021
PRIMARY
ChEMBL
CHEMBL3545022
Created by admin on Sat Jun 26 09:24:56 UTC 2021 , Edited by admin on Sat Jun 26 09:24:56 UTC 2021
PRIMARY
FDA UNII
16ZDH50O1U
Created by admin on Sat Jun 26 09:24:56 UTC 2021 , Edited by admin on Sat Jun 26 09:24:56 UTC 2021
PRIMARY
DRUG BANK
DB13930
Created by admin on Sat Jun 26 09:24:56 UTC 2021 , Edited by admin on Sat Jun 26 09:24:56 UTC 2021
PRIMARY
INN
9969
Created by admin on Sat Jun 26 09:24:56 UTC 2021 , Edited by admin on Sat Jun 26 09:24:56 UTC 2021
PRIMARY
PUBCHEM
11719003
Created by admin on Sat Jun 26 09:24:56 UTC 2021 , Edited by admin on Sat Jun 26 09:24:56 UTC 2021
PRIMARY
CAS
869886-67-9
Created by admin on Sat Jun 26 09:24:56 UTC 2021 , Edited by admin on Sat Jun 26 09:24:56 UTC 2021
PRIMARY
Related Record Type Details
TRANSPORTER -> INHIBITOR
In ABCB1-overexpressing cells, ulixertinib antagonized MDR by attenuating the efflux function of ABCB1. A combination of ulixertinib with anticancer drugs to attenuate MDR mediated by ABCB1 or ABCG2 in cancer cells overexpressing these transporters.
TARGET -> INHIBITOR
REVERSIBLE
Ki
TRANSPORTER -> INHIBITOR
In ABCG2-overexpressing cells, ulixertinib inhibited the efflux activity of ABCG2 and reversed resistance to sub-strate anticancer drugs. Mechanistic investigations revealed that ulixertinib stimulated the ATPase activity of both ABCB1 and ABCG2 in a concentration-dependent manner,
TARGET -> INHIBITOR
competitive with ATP increases in ATP led to increased IC50. Value for 1 micromolar ATP
REVERSIBLE
IC50
TARGET -> INHIBITOR
REVERSIBLE
Ki
SALT/SOLVATE -> PARENT
Related Record Type Details
ACTIVE MOIETY