ensartinib   Click here for help

GtoPdb Ligand ID: 8959

Synonyms: Ensacove® | Example 18 [WO2012048259] [3] | X-396
Approved drug
ensartinib is an approved drug (FDA (2024))
Compound class: Synthetic organic
Comment: Ensartinib (X-396) is an orally available, investigational inhibitor of anaplastic lymphoma receptor tyrosine kinase (ALK). It blocks ALK-mediated signalling and inhibits proliferation in tumours harbouring ALK fusions and mutations [4].
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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

ensartinib is commercially available from our sponsors

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 Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). 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 8
Hydrogen bond donors 2
Rotatable bonds 8
Topological polar surface area 113.68
Molecular weight 546.13
XLogP 3.66
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
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.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES CN1CCN(CC1)C(=O)c1ccc(cc1)NC(=O)c1nnc(c(c1)OC(c1c(Cl)ccc(c1Cl)F)C)N
Isomeric SMILES CN1CCN(CC1)C(=O)c1ccc(cc1)NC(=O)c1nnc(c(c1)O[C@@H](c1c(Cl)ccc(c1Cl)F)C)N
InChI InChI=1S/C25H25Cl2FN6O3/c1-14(21-17(26)7-8-18(28)22(21)27)37-20-13-19(31-32-23(20)29)24(35)30-16-5-3-15(4-6-16)25(36)34-11-9-33(2)10-12-34/h3-8,13-14H,9-12H2,1-2H3,(H2,29,32)(H,30,35)/t14-/m1/s1
InChI Key ONPGOSVDVDPBCY-CQSZACIVSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
References
1. Ding L, Yuan X, Wang Y, Yang M, Wu P, Chen H, Yun Y, Shen Z, Ji D, Ma Y. (2024)
Ensartinib in the treatment of anaplastic lymphoma kinase-positive locally advanced or metastatic patients with lung squamous or adenosquamous carcinoma: A real-world, retrospective study.
Asia Pac J Clin Oncol, 20 (6): 700-706. [PMID:38898784]
2. Horn L, Wang Z, Wu G, Poddubskaya E, Mok T, Reck M, Wakelee H, Chiappori AA, Lee DH, Breder V et al.. (2021)
Ensartinib vs Crizotinib for Patients With Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer: A Randomized Clinical Trial.
JAMA Oncol, 7 (11): 1617-1625. [PMID:34473194]
3. Liang C. (2012)
Substituted pyridazine carboxamide compounds.
Patent number: WO2012048259. Assignee: Xcovery Holding Company, Llc. Priority date: 08/10/2010. Publication date: 12/04/2012.
4. Lovly CM, Heuckmann JM, de Stanchina E, Chen H, Thomas RK, Liang C, Pao W. (2011)
Insights into ALK-driven cancers revealed through development of novel ALK tyrosine kinase inhibitors.
Cancer Res, 71 (14): 4920-31. [PMID:21613408]
5. Singhi EK, Horn L. (2018)
Background and rationale of the eXalt3 trial investigating X-396 in the treatment of ALK+ non-small-cell lung cancer.
Future Oncol, 14 (18): 1781-1787. [PMID:29506392]
6. Xu H, Chen T, Zheng Y, Fang W. (2024)
Ensartinib rapidly relieves symptoms in ALK-positive patients with brain metastases.
Asian J Surg, 47 (9): 3947-3949. [PMID:38749835]
7. Zhao M, Shao T, Shao H, Zhou C, Tang W. (2024)
Identifying optimal ALK inhibitors in first- and second-line treatment of patients with advanced ALK-positive non-small-cell lung cancer: a systematic review and network meta-analysis.
BMC Cancer, 24 (1): 186. [PMID:38331773]