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Purity: ≥98%
Olmutinib (also known as HM61713 and BI-1482694; Olita) is a novel, potent, orally bioavailable, third-generation and irreversible EFGR/epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI). It binds to a cysteine residue near the kinase domain via a covalent bond which is irreveisible. Olmutinib is being developed by Boehringer Ingelheim and Hanmi Pharmaceutical Co. Ltd for the treatment of non-small cell lung cancer (NSCLC). Third-generation EGFR TKIs with covalent binding to the receptors demonstrate irreversible enzymatic inhibition of activating EGFR mutations and T790M mutation (a common reason for acquired EGFR TKI resistance), while sparing wild-type EGFR. In December 2015, olmutinib was granted breakthrough therapy designation in NSCLC by the US FDA. In May 2016, olmutinib received its first global approval in South Korea for the treatment of patients with locally advanced or metastatic EGFR T790M mutation-positive NSCLC.
| ln Vitro |
In HCC827 cells expressing EGFRDEL19 (IC50=9.2 nM) and H1975 cells expressing EGFRL858R/T790M (IC50=10 nM), olmutinib potently suppresses EGFR. By contrast, olmutinib's IC50 against EGFRWT-expressing cells is 2225 nM [1].
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| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
tmax of 3-4h with oral administration. Data not yet available. Data not yet available. Data not yet available. Metabolism / Metabolites Data not yet available. Biological Half-Life 8-11h. |
| Toxicity/Toxicokinetics |
Protein Binding
Data not yet available. |
| References | |
| Additional Infomation |
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. 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.
Olmutinib is an orally available small molecule, mutant-selective inhibitor of epidermal growth factor receptor (EGFR) with potential antineoplastic activity. Olmutinib binds to and inhibits mutant forms of EGFR, thereby leading to cell death of EGFR-expressing tumor cells. As this agent is selective towards mutant forms of EGFR, its toxicity profile may be reduced as compared to non-selective EGFR inhibitors which also inhibit the EGFR wild type form. Drug Indication For use in treatment of metastatic T790M mutation positive non-small cell lung cancer. Mechanism of Action Olmutinib covalently binds a cysteine residue near the kinase domain of mutant EGFRs to prevent phosphorylation of the receptor. This inhibits receptor signalling as phosphorylation is necessary for recruitment of signalling cascade proteins. 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. By inhibiting EGFR activation, olmutinib attenuates the activation of these tumor promoting pathways. |
| Molecular Formula |
C26H26N6O2S
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|---|---|
| Molecular Weight |
486.5886
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| Exact Mass |
486.183
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| CAS # |
1353550-13-6
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| Related CAS # |
1842366-97-5 (2HCl);2102670-48-2 (HCl);1353550-13-6;2102714-68-9 (HCl hydrate);
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| PubChem CID |
54758501
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Index of Refraction |
1.706
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| LogP |
4.95
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
35
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| Complexity |
712
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
FDMQDKQUTRLUBU-UHFFFAOYSA-N
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| InChi Code |
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)
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| Chemical Name |
N-(3-((2-((4-(4-methylpiperazin-1-yl)phenyl)amino)thieno[3,2-d]pyrimidin-4-yl)oxy)phenyl)acrylamide
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| Synonyms |
BI 1482694; HM61713; BI-1482694; HM 61713; BI1482694; HM-61713
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~125 mg/mL (~256.89 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 6.25 mg/mL (12.84 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 62.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 6.25 mg/mL (12.84 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 62.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: 6.25 mg/mL (12.84 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0551 mL | 10.2756 mL | 20.5512 mL | |
| 5 mM | 0.4110 mL | 2.0551 mL | 4.1102 mL | |
| 10 mM | 0.2055 mL | 1.0276 mL | 2.0551 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
 The structure ofolmutiniband cytotoxicity ofolmutinib.Acta Pharm Sin B.2018 Jul;8(4):563-574. |
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 Olmutinibenhanced the anticancer effect of topotecan in the S1-MI-80 cell xenograft model in nude mice.Acta Pharm Sin B.2018 Jul;8(4):563-574. |
 Effect ofolmutinibon the expression of ABCG2 in MDR cells.Acta Pharm Sin B.2018 Jul;8(4):563-574. |
 Effect ofolmutinibon the intracellular accumulation of DOX, Rho 123 in MDR cells and their parental cells.Acta Pharm Sin B.2018 Jul;8(4):563-574. |
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 Effect ofolmutinibon the efflux of Rho 123, the ATPase activity and the [125I]-IAAP photoaffinity labeling of ABCG2.
Acta Pharm Sin B.2018 Jul;8(4):563-574. |
 Effect ofolmutinibon AKT, ERK, and their phosphorylations in MDR and the parental cells.Acta Pharm Sin B.2018 Jul;8(4):563-574. |
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