Olmutinib

Identification

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Name
Olmutinib
Accession Number
DB13164
Type
Small Molecule
Groups
Investigational
Description

Olmutinib is an orally active epidermal growth factor receptor inhibitor used in the treatment of T790M mutation positive non-small cell lung cancer. It is available under the brand name Olita made by Hanmi Pharmaceuticals 4. Olmutinib was developed by Hanmi Pharmaceuticals and Boehringer Ingelheim. Olmutinib recieved breakthrough therapy designation in the United States in December 2015 and was approved for use in Korea in May 2016.

Structure
Thumb
Synonyms
Not Available
External IDs
BI 1482694 / BI-1482694 / HM-61713 / HM61713
Categories
UNII
CHL9B67L95
CAS number
1353550-13-6
Weight
Average: 486.59
Monoisotopic: 486.183795275
Chemical Formula
C26H26N6O2S
InChI Key
FDMQDKQUTRLUBU-UHFFFAOYSA-N
InChI
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)
IUPAC Name
N-{3-[(2-{[4-(4-methylpiperazin-1-yl)phenyl]amino}thieno[3,2-d]pyrimidin-4-yl)oxy]phenyl}prop-2-enamide
SMILES
CN1CCN(CC1)C1=CC=C(NC2=NC(OC3=CC=CC(NC(=O)C=C)=C3)=C3SC=CC3=N2)C=C1

Pharmacology

Indication

For use in treatment of metastatic T790M mutation positive non-small cell lung cancer 4.

Pharmacodynamics

Olmutinib selectively and irreversibly binds and inhibits epidermal growth factor receptors (EGFR) with the T790M activating mutation. 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 5 6. By inhibiting EGFR activation, olmutinib attenuates the activation of these tumor promoting pathways.

Mechanism of action

Olmutinib covalently binds a cysteine residue near the kinase domain of mutant EGFRs to prevent phosphorylation of the receptor 7. This inhibits receptor signalling as phosphorylation is necessary for recruitment of signalling cascade proteins.

TargetActionsOrganism
AEpidermal growth factor receptor
inhibitor
Humans
Absorption

tmax of 3-4h with oral administration 8.

Volume of distribution

Data not yet available.

Protein binding

Data not yet available.

Metabolism

Data not yet available.

Route of elimination

Data not yet available.

Half life

8-11h 8.

Clearance

Data not yet available.

Toxicity

No toxicological investigation has been completed.

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Liao BC, Lin CC, Lee JH, Yang JC: Update on recent preclinical and clinical studies of T790M mutant-specific irreversible epidermal growth factor receptor tyrosine kinase inhibitors. J Biomed Sci. 2016 Dec 3;23(1):86. [PubMed:27912760]
  2. Wang S, Cang S, Liu D: Third-generation inhibitors targeting EGFR T790M mutation in advanced non-small cell lung cancer. J Hematol Oncol. 2016 Apr 12;9:34. doi: 10.1186/s13045-016-0268-z. [PubMed:27071706]
  3. Tan CS, Cho BC, Soo RA: Next-generation epidermal growth factor receptor tyrosine kinase inhibitors in epidermal growth factor receptor -mutant non-small cell lung cancer. Lung Cancer. 2016 Mar;93:59-68. doi: 10.1016/j.lungcan.2016.01.003. Epub 2016 Jan 8. [PubMed:26898616]
  4. Kim ES: Olmutinib: First Global Approval. Drugs. 2016 Jul;76(11):1153-7. doi: 10.1007/s40265-016-0606-z. [PubMed:27357069]
  5. Suzuki M, Shigematsu H, Hiroshima K, Iizasa T, Nakatani Y, Minna JD, Gazdar AF, Fujisawa T: Epidermal growth factor receptor expression status in lung cancer correlates with its mutation. Hum Pathol. 2005 Oct;36(10):1127-34. [PubMed:16226114]
  6. Bogdan S, Klambt C: Epidermal growth factor receptor signaling. Curr Biol. 2001 Apr 17;11(8):R292-5. [PubMed:11369216]
  7. Kwang O-K, Cha MY, Kim M, Song JY, Lee J-H, Kim YH, Lee Y-M, Suh KH, Son J.: Abstract LB-100: Discovery of HM61713 as an orally available and mutant EGFR selective inhibitor Cancer Res. 2014 October;74(19 Suppl.):Abstract nr LB-100.
  8. Hanmi Pharmaceutical Olmutinib Phase I Poster [Link]
External Links
KEGG Drug
D10859
PubChem Compound
54758501
PubChem Substance
347829271
ChemSpider
45743494
BindingDB
50160871
ChEMBL
CHEMBL3786343
Wikipedia
Olmutinib
ATC Codes
L01XE40 — Olmutinib
MSDS
Download (27.4 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentHealthy Volunteers1
1, 2CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2Active Not RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)2
2CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00792 mg/mLALOGPS
logP5.22ALOGPS
logP5.47ChemAxon
logS-4.8ALOGPS
pKa (Strongest Acidic)13.85ChemAxon
pKa (Strongest Basic)7.96ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area82.62 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity140.67 m3·mol-1ChemAxon
Polarizability53.21 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenylpiperazines. These are compounds containing a phenylpiperazine skeleton, which consists of a piperazine bound to a phenyl group.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazinanes
Sub Class
Piperazines
Direct Parent
Phenylpiperazines
Alternative Parents
N-arylpiperazines / Diarylethers / Anilides / Thienopyrimidines / Aniline and substituted anilines / Dialkylarylamines / N-arylamides / Phenol ethers / Phenoxy compounds / N-methylpiperazines
show 13 more
Substituents
Phenylpiperazine / N-arylpiperazine / Diaryl ether / Thienopyrimidine / Anilide / Phenol ether / Phenoxy compound / Tertiary aliphatic/aromatic amine / N-arylamide / Dialkylarylamine
show 29 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Ubiquitin protein ligase binding
Specific Function
Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TG...
Gene Name
EGFR
Uniprot ID
P00533
Uniprot Name
Epidermal growth factor receptor
Molecular Weight
134276.185 Da
References
  1. Tan CS, Cho BC, Soo RA: Next-generation epidermal growth factor receptor tyrosine kinase inhibitors in epidermal growth factor receptor -mutant non-small cell lung cancer. Lung Cancer. 2016 Mar;93:59-68. doi: 10.1016/j.lungcan.2016.01.003. Epub 2016 Jan 8. [PubMed:26898616]
  2. Kwang O-K, Cha MY, Kim M, Song JY, Lee J-H, Kim YH, Lee Y-M, Suh KH, Son J.: Abstract LB-100: Discovery of HM61713 as an orally available and mutant EGFR selective inhibitor Cancer Res. 2014 October;74(19 Suppl.):Abstract nr LB-100.

Drug created on January 20, 2017 14:12 / Updated on June 04, 2019 07:48