Olmutinib
Identification
- Generic Name
- Olmutinib
- DrugBank Accession Number
- DB13164
- Background
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.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
- Weight
- Average: 486.59
Monoisotopic: 486.183795275 - Chemical Formula
- C26H26N6O2S
- Synonyms
- Olmutinib
- External IDs
- BI 1482694
- BI-1482694
- HM-61713
- HM61713
Pharmacology
- Indication
For use in treatment of metastatic T790M mutation positive non-small cell lung cancer 4.
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- 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.
Target Actions Organism AEpidermal growth factor receptor inhibitorHumans - 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.
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
No toxicological investigation has been completed.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAmbroxol The risk or severity of methemoglobinemia can be increased when Olmutinib is combined with Ambroxol. Articaine The risk or severity of methemoglobinemia can be increased when Olmutinib is combined with Articaine. Benzocaine The risk or severity of methemoglobinemia can be increased when Olmutinib is combined with Benzocaine. Benzyl alcohol The risk or severity of methemoglobinemia can be increased when Olmutinib is combined with Benzyl alcohol. Bupivacaine The risk or severity of methemoglobinemia can be increased when Olmutinib is combined with Bupivacaine. - Food Interactions
- Not Available
Categories
- ATC Codes
- L01EB06 — Olmutinib
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- 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
- Acrylic acid or derivatives / Amine / Amino acid or derivatives / Aminopyrimidine / Anilide / Aniline or substituted anilines / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Carbonyl group show 29 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- CHL9B67L95
- CAS number
- 1353550-13-6
- 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
References
- General References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Kim ES: Olmutinib: First Global Approval. Drugs. 2016 Jul;76(11):1153-7. doi: 10.1007/s40265-016-0606-z. [Article]
- 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. [Article]
- Bogdan S, Klambt C: Epidermal growth factor receptor signaling. Curr Biol. 2001 Apr 17;11(8):R292-5. [Article]
- 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. [Article]
- Hanmi Pharmaceutical Olmutinib Phase I Poster [Link]
- External Links
- KEGG Drug
- D10859
- PubChem Compound
- 54758501
- PubChem Substance
- 347829271
- ChemSpider
- 45743494
- BindingDB
- 50160871
- ChEMBL
- CHEMBL3786343
- ZINC
- ZINC000198970879
- Wikipedia
- Olmutinib
- MSDS
- Download (27.4 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 2 Completed Treatment Non-Small Cell Lung Cancer (NSCLC) 2 2 Terminated Treatment Non-Small Cell Lung Cancer (NSCLC) 1 1 Completed Treatment Healthy Subjects (HS) 2 1 Terminated Treatment Non-Small Cell Lung Cancer (NSCLC) 1 1, 2 Completed Treatment Non-Small Cell Lung 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
Property Value Source Water Solubility 0.00792 mg/mL ALOGPS logP 5.22 ALOGPS logP 5.47 Chemaxon logS -4.8 ALOGPS pKa (Strongest Acidic) 13.85 Chemaxon pKa (Strongest Basic) 7.96 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 6 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 82.62 Å2 Chemaxon Rotatable Bond Count 7 Chemaxon Refractivity 140.67 m3·mol-1 Chemaxon Polarizability 53.21 Å3 Chemaxon Number of Rings 5 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0a4r-0000900000-cac3abed5a041598619f Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0019-0000900000-2e806de63f674a8591c3 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0aor-0200900000-888eff1202683d62314e Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-001i-0000900000-d38d1ee7b2c02c3e0ffa Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-053i-0005900000-0c1826a7d1f3c5823e0b Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-000l-3621900000-f6ed5663d3221e90a553 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 210.44246 predictedDeepCCS 1.0 (2019) [M+H]+ 212.83801 predictedDeepCCS 1.0 (2019) [M+Na]+ 218.75055 predictedDeepCCS 1.0 (2019)
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
- 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
- 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. [Article]
- 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. [Article]
Drug created at January 20, 2017 21:12 / Updated at February 21, 2021 18:54