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AZD1390

Name: AZD1390
Brand: Selleck Chemicals
SKU: S8680
Rating: 5 (23 reviews)

Catalog No.S8680 Purity:99.99%

AZD1390 is a first-in-class orally available and CNS penetrant ATM inhibitor with an IC50 of 0.78 nM in cells and >10,000-fold selectivity over closely related members of the PIKK family of enzymes and excellent selectivity across a broad panel of kinases.

AZD1390 Chemical Structure

CAS No. 2089288-03-7

Purity & Quality Control

Batch: Purity: 99.99%

99.99

AZD1390 Related Products

Related Targets	ATM ATR	Click to Expand
Related Products	KU-55933 VE-821 KU-60019 Berzosertib (VE-822) Ceralasertib (AZD6738) AZ20 AZD0156 Mirin CP-466722 Elimusertib (BAY-1895344) hydrochloride ETP-46464 Elimusertib (BAY-1895344) CGK 733 VX-803 (M4344) AZ31 AZ32 HAMNO	Click to Expand
Related Compound Libraries	Kinase Inhibitor Library PI3K/Akt Inhibitor Library Apoptosis Compound Library Cell Cycle compound library NF-κB Signaling Compound Library	Click to Expand

Signaling Pathway

ATM/ATR Signaling Pathway

Biological Activity

Description

Targets

ATM ^[1]
(Cell-based assay)

0.78 nM

In vitro
In vitro	AZD1390 blocks ATM-dependent DDR (DNA damage response) pathway activity and combines with radiation to induce G2 cell cycle phase accumulation, micronuclei, and apoptosis. AZD1390 radiosensitizes glioma and lung cancer cell lines, with p53 mutant glioma cells generally being more radiosensitized than wild type. AZD1390 results in increased genome instability^[2].
Cell Research	Cell lines	NCI-H2228 cells
	Concentrations	0-1250 nM
	Incubation Time	1 h
	Method	Cells (3000 per well) are seeded in a 384-well format in RPMI with 10% fetal bovine serum.After 24 hours, plates are Echo-dosed with a semi-log dose dilution of each compound from a top concentration of 1250 nM. One hour after compound dosing, plates are irradiated with 0, 2.5, or 4 Gy. At 1, 6, 24, and 48 hours after irradiation, plates are fixed by adding a 1:1 volume of 8% PFA directly to the medium to give a final concentration of 4% PFA and incubated for 30 min at room temperature before washing three times with phosphate-buffered saline solution (PBSA).
Experimental Result Images	Methods	Biomarkers	Images	PMID
Experimental Result Images	Western blot	pChk2 pATM (S1981) / ATM / pKAP1(S824) / KAP1 / pCDK1		29938225

In Vivo
In vivo	AZD1390 displays excellent oral bioavailability in preclinical species (66% in rat and 74% in dog). It can efficiently cross the BBB in non-human primate PET studies. Profound tumor regressions and increased animal survival (>50 days) have been observed in orthotopic xenograft models of brain cancer following just 2 or 4 days combination treatment of AZD1390 with radiotherapy, compared to radiotherapy treatment alone^[1]. In in vivo syngeneic and patient-derived glioma as well as orthotopic lung-brain metastatic models, AZD1390 dosed in combination with daily fractions of IR (whole-brain or stereotactic radiotherapy) significantly induces tumor regressions and increased animal survival compared to IR treatment alone. AZD1390 has favorable physical, chemical, PK, and PD properties suitable for clinical applications that require exposures within the central nervous system^[2].
Animal Research	Animal Models	a lung NCI-H2228 xenograftmodel either implanted into nude mice brains directly (intracranial brain) or injected into the carotid artery [intracarotid artery (ICA)]
	Dosages	5, 15 and 20 mg/kg
	Administration	by oral gavage

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT05182905	Recruiting	Glioblastoma\|Glioma\|Glioblastoma Multiforme\|Glioma Malignant	Nader Sanai\|Barrow Neurological Institute\|Ivy Brain Tumor Center\|AstraZeneca\|St. Joseph''s Hospital and Medical Center Phoenix	March 9 2022	Early Phase 1
NCT03423628	Recruiting	Recurrent Glioblastoma Multiforme\|Primary Glioblastoma Multiforme\|Brain Neoplasms Malignant\|Leptomeningeal Disease (LMD)	AstraZeneca	April 2 2018	Phase 1
NCT03215381	Completed	Healthy Volunteer Male Subjects	AstraZeneca\|Karolinska Institutet Quintiles IMS	October 10 2017	Phase 1

References

Chemical Information & Solubility

Molecular Weight	477.57	Formula	C₂₇H₃₂FN₅O₂
CAS No.	2089288-03-7	SDF	--
Smiles	CC(C)N1C2=C(C=NC3=CC(=C(C=C32)C4=CN=C(C=C4)OCCCN5CCCCC5)F)N(C1=O)C
Storage (From the date of receipt)	3 years-20°Cpowder	Storage of Stock Solutions Aliquot the stock solutions to avoid repeated freeze-thaw cycles	1 year-80°Cin solvent
Storage (From the date of receipt)	3 years-20°Cpowder		1 month-20°Cin solvent

In vitro
Batch:

Ethanol : 95 mg/mL

DMSO : 14 mg/mL ( (29.31 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Molecular Weight Calculator

In vivo Batch: Add solvents to the product individually and in order.				In vivo Formulation Calculator
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	10%DMSO 1 40%PEG300 2 5%TWEEN80 3 45%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	1.500mg/ml (3.14mM)	Taking the 1 mL working solution as an example, add 100 μL of 15 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 450 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

Preparing Stock Solutions

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
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Dilution Calculator Molecular Weight Calculator

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3
If you have any other enquiries, please leave a message.

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