mobocertinib   Click here for help

GtoPdb Ligand ID: 10468

Synonyms: AP32788 | example 94 [WO2015195228A1] | Exkivity® | TAK-788 | TAK788
Approved drug
mobocertinib is an approved drug (FDA (2021))
Compound class: Synthetic organic
Comment: Mobocertinib (TAK-788) is an oral EGFR/HER2 tyrosine kinase inhibitor that is claimed in Ariad Pharmaceuticals' patent WO2015195228A1 [2]. It inhibits EGFR and HER2 with activating/resistance mutations, including rare EGFR Ins20 (exon 20 insertion) resistance mutations [1,3] and was progressed by Takeda Pharmaceuticals as an advanced therapy for metastatic NSCLC with this exon 20 insertion [4-5].
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Click here for structure editor
Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 9
Hydrogen bond donors 2
Rotatable bonds 14
Topological polar surface area 113.85
Molecular weight 585.31
XLogP 4.42
No. Lipinski's rules broken 1
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES C=CC(=O)Nc1cc(Nc2ncc(c(n2)c2cn(c3c2cccc3)C)C(=O)OC(C)C)c(cc1N(CCN(C)C)C)OC
Isomeric SMILES C=CC(=O)Nc1cc(Nc2ncc(c(n2)c2cn(c3c2cccc3)C)C(=O)OC(C)C)c(cc1N(CCN(C)C)C)OC
InChI InChI=1S/C32H39N7O4/c1-9-29(40)34-24-16-25(28(42-8)17-27(24)38(6)15-14-37(4)5)35-32-33-18-22(31(41)43-20(2)3)30(36-32)23-19-39(7)26-13-11-10-12-21(23)26/h9-13,16-20H,1,14-15H2,2-8H3,(H,34,40)(H,33,35,36)
InChI Key AZSRSNUQCUDCGG-UHFFFAOYSA-N
References
1. Han H, Li S, Chen T, Fitzgerald M, Liu S, Peng C, Tang KH, Cao S, Chouitar J, Wu J et al.. (2021)
Targeting HER2 Exon 20 Insertion-Mutant Lung Adenocarcinoma with a Novel Tyrosine Kinase Inhibitor Mobocertinib.
Cancer Res, 81 (20): 5311-5324. [PMID:34380634]
2. Huang W-S, Gong Y, Li F, Bencivenga NE, Dalgarno DC, Kohlmann A, Shakespeare WC, Thomas RM, Zhu X, West AV et al.. (2015)
Heteroaryl compounds for kinase inhibition.
Patent number: WO2015195228A1. Assignee: Ariad Pharmaceuticals, Inc.. Priority date: 19/06/2014. Publication date: 23/12/2015.
3. Pacheco JM. (2021)
Mobocertinib: A Potential Treatment for NSCLC with EGFR Exon 20 Insertions.
Cancer Discov, 11 (7): 1617-1619. [PMID:34284994]
4. Remon J, Hendriks LEL, Cardona AF, Besse B. (2020)
EGFR exon 20 insertions in advanced non-small cell lung cancer: A new history begins.
Cancer Treat Rev, 90: 102105. [PMID:32979839]
5. Zhang SS, Zhu VW. (2021)
Spotlight on Mobocertinib (TAK-788) in NSCLC with EGFR Exon 20 Insertion Mutations.
Lung Cancer (Auckl), 12: 61-65. [PMID:34285620]