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Details

Stereochemistry ACHIRAL
Molecular Formula C26H26N6O2S
Molecular Weight 486.5907
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of OLMUTINIB

SMILES

C=CC(=Nc1cccc(c1)Oc2c3c(ccs3)nc(Nc4ccc(cc4)N5CCN(C)CC5)n2)O

InChI

InChIKey=FDMQDKQUTRLUBU-UHFFFAOYSA-N
InChI=1S/C26H26N6O2S/c1-3-23(33)27-19-5-4-6-21(17-19)34-25-24-22(11-16-35-24)29-26(30-25)28-18-7-9-20(10-8-18)32-14-12-31(2)13-15-32/h3-11,16-17H,1,12-15H2,2H3,(H,27,33)(H,28,29,30)

HIDE SMILES / InChI

Molecular Formula C26H26N6O2S
Molecular Weight 486.5907
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: The description was created based on several sources, including https://www.drugbank.ca/drugs/DB13164 | https://clinicaltrials.gov/ct2/show/record/NCT02485652 | https://www.google.com/patents/WO2011162515A3

Olmutinib is a novel third-generation epidermal growth factor receptor (EGFR) mutation-specific tyrosine kinase inhibitor, used in the treatment of T790M mutation positive non-small cell lung cancer. Olmutinib covalently binds a cysteine residue near the kinase domain of mutant EGFRs to prevent phosphorylation of the receptor. EGFRs are frequently over-expressed in lung cancer and contribute to activation of the phosphoinositide 3-kinase and mitogen-activated protein kinase pathways which both promote cell survival and proliferation. By inhibiting EGFR activation, Olmutinib attenuates the activation of these tumor-promoting pathways. In the first phase I/II clinical study of Osimertinib, 800 mg/ day was chosen as the dose for subsequent studies, and the dose-limiting toxicity and maximum tolerated dose was not reached. Olmutinib received breakthrough therapy designation in the United States in December 2015 and was approved for use in Korea in May 2016.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
10.0 nM [IC50]
1.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Structure-based discovery of novel 4,5,6-trisubstituted pyrimidines as potent covalent Bruton's tyrosine kinase inhibitors.
2016 Jul 1
Patents

Patents

Sample Use Guides

800 mg QD (2 x 400 mg tablets) continuously in 21-day cycles
Route of Administration: Oral
Olmutinib was evaluated with the BTK kinase inhibition using Z'-LYTE™ fluorescence resonance energy transfer (FRET) method and ibrutinib was used as the reference compounds. The Z'-LYTE™ biochemical assay employs a FRET-based, coupled-enzyme format and is based on the differential sensitivity of phosphorylated and non-phosphorylated peptides to proteolytic cleavage. The peptide substrate is labeled with two fluorophores-one at each end-that make up a FRET pair. In the primary reaction (the Kinase Reaction), the kinase transfers the g-phosphate of ATP to a single serine or threonine residue in the synthetic peptide substrate. In the secondary reaction (the Development Reaction), a site-specific protease (the Development Reagent) recognizes and cleaves nonphosphorylated peptides. Phosphorylated peptides exhibit suppressed cleavage by the Development Reagent. Cleavage disrupts FRET between the donor (i.e., coumarin) and acceptor (i.e., fluorescein) fluorophores on the peptide, whereas uncleaved, phosphorylated peptides maintain FRET. A ratiometric method, which calculates the ratio (the Emission Ratio) of donor emission to acceptor emission after excitation of the donor fluorophore at 400 nm
Substance Class Chemical
Created
by admin
on Sat Jun 26 13:41:56 UTC 2021
Edited
by admin
on Sat Jun 26 13:41:56 UTC 2021
Record UNII
CHL9B67L95
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
OLMUTINIB
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
OLMUTINIB [USAN]
Common Name English
N-(3-((2-(4-(4-METHYLPIPERAZIN-1-YL)ANILINO)THIENO(3,2-D)PYRIMIDIN-4-YL)OXY)PHENYL)PROP-2-ENAMIDE
Systematic Name English
BI 1482694
Code English
BI-1482694
Code English
OLMUTINIB [INN]
Common Name English
2-PROPENAMIDE, N-(3-((2-((4-(4-METHYL-1-PIPERAZINYL)PHENYL)AMINO)THIENO(3,2-D)PYRIMIDIN-4-YL)OXY)PHENYL)-
Systematic Name English
OLMUTINIB [WHO-DD]
Common Name English
HM-61713
Code English
HM61713
Code English
Classification Tree Code System Code
NCI_THESAURUS C2167
Created by admin on Sat Jun 26 13:41:56 UTC 2021 , Edited by admin on Sat Jun 26 13:41:56 UTC 2021
NCI_THESAURUS C129825
Created by admin on Sat Jun 26 13:41:56 UTC 2021 , Edited by admin on Sat Jun 26 13:41:56 UTC 2021
WHO-ATC L01XE40
Created by admin on Sat Jun 26 13:41:56 UTC 2021 , Edited by admin on Sat Jun 26 13:41:56 UTC 2021
Code System Code Type Description
DRUG CENTRAL
5210
Created by admin on Sat Jun 26 13:41:56 UTC 2021 , Edited by admin on Sat Jun 26 13:41:56 UTC 2021
PRIMARY
EVMPD
SUB182705
Created by admin on Sat Jun 26 13:41:56 UTC 2021 , Edited by admin on Sat Jun 26 13:41:56 UTC 2021
PRIMARY
FDA UNII
CHL9B67L95
Created by admin on Sat Jun 26 13:41:56 UTC 2021 , Edited by admin on Sat Jun 26 13:41:56 UTC 2021
PRIMARY
CAS
1353550-13-6
Created by admin on Sat Jun 26 13:41:56 UTC 2021 , Edited by admin on Sat Jun 26 13:41:56 UTC 2021
PRIMARY
ChEMBL
CHEMBL3545430
Created by admin on Sat Jun 26 13:41:56 UTC 2021 , Edited by admin on Sat Jun 26 13:41:56 UTC 2021
PRIMARY
NCI_THESAURUS
C101791
Created by admin on Sat Jun 26 13:41:56 UTC 2021 , Edited by admin on Sat Jun 26 13:41:56 UTC 2021
PRIMARY
PUBCHEM
54758501
Created by admin on Sat Jun 26 13:41:56 UTC 2021 , Edited by admin on Sat Jun 26 13:41:56 UTC 2021
PRIMARY
DRUG BANK
DB13164
Created by admin on Sat Jun 26 13:41:56 UTC 2021 , Edited by admin on Sat Jun 26 13:41:56 UTC 2021
PRIMARY
INN
10093
Created by admin on Sat Jun 26 13:41:56 UTC 2021 , Edited by admin on Sat Jun 26 13:41:56 UTC 2021
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
TARGET -> INHIBITOR
IRREVERSIBLE INHIBITOR
TARGET -> INHIBITOR
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ACTIVE MOIETY