AZD1390   Click here for help

GtoPdb Ligand ID: 11277

Compound class: Synthetic organic
Comment: AZD1390 is an oral, brain-penetrant ATM kinase inhibitor [2]. Structurally, AZD1390 is from the same chemical series as AZD0156, but is optimised to cross the blood-brain barrier [3-4]. Mechanistically, blocking ATM disrupts DNA damage repair and sensitises cancer cells to radiotherapy. This induces G2 cell cycle arrest and the development of micronuclei, and ultimately leads to apoptosis. Experimental evidence suggests that AZD1390 is able to promote neurite outgrowth in vitro, and axon regeneration and functional recovery in in vivo models of spinal cord injury [1].
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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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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 Fc1cc2ncc3c(c2cc1c1ccc(nc1)OCCCN1CCCCC1)n(C(C)C)c(=O)n3C
Isomeric SMILES Fc1cc2ncc3c(c2cc1c1ccc(nc1)OCCCN1CCCCC1)n(C(C)C)c(=O)n3C
InChI InChI=1S/C27H32FN5O2/c1-18(2)33-26-21-14-20(22(28)15-23(21)29-17-24(26)31(3)27(33)34)19-8-9-25(30-16-19)35-13-7-12-32-10-5-4-6-11-32/h8-9,14-18H,4-7,10-13H2,1-3H3
InChI Key VQSZIPCGAGVRRP-UHFFFAOYSA-N
References
1. Ahmed Z, Tuxworth RI. (2022)
The brain-penetrant ATM inhibitor, AZD1390, promotes axon regeneration and functional recovery in preclinical models of spinal cord injury.
Clin Transl Med, 12 (7): e962. [PMID:35818848]
2. Durant ST, Zheng L, Wang Y, Chen K, Zhang L, Zhang T, Yang Z, Riches L, Trinidad AG, Fok JHL et al.. (2018)
The brain-penetrant clinical ATM inhibitor AZD1390 radiosensitizes and improves survival of preclinical brain tumor models.
Sci Adv, 4 (6): eaat1719. [PMID:29938225]
3. Jucaite A, Stenkrona P, Cselényi Z, De Vita S, Buil-Bruna N, Varnäs K, Savage A, Varrone A, Johnström P, Schou M et al.. (2021)
Brain exposure of the ATM inhibitor AZD1390 in humans-a positron emission tomography study.
Neuro Oncol, 23 (4): 687-696. [PMID:33123736]
4. Talele S, Zhang W, Chen J, Gupta SK, Burgenske DM, Sarkaria JN, Elmquist WF. (2022)
Central Nervous System Distribution of the Ataxia-Telangiectasia Mutated Kinase Inhibitor AZD1390: Implications for the Treatment of Brain Tumors.
J Pharmacol Exp Ther, 383 (1): 91-102. [PMID:36137710]