AZD1390

Name: AZD1390
Brand: Selleck Chemicals
SKU: S8680
Rating: 5 (1 reviews)

For research use only.

Catalog No.S8680

1 publication

CAS No. 2089288-03-7

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.

Selleck's AZD1390 has been cited by 1 publication

Cell Death Differ, 2019, 10.1038/s41418-019-0393-7

PubMed: 31320750

Purity & Quality Control

Choose Selective ATM/ATR Inhibitors

Biological Activity

Description

Targets

ATM ^[1]
(Cell-based assay)

0.78 nM

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].

Assay

Methods	Test Index	PMID
Western blot	pATM (S1981) / ATM / pKAP1(S824) / KAP1 / pCDK1 ; PubMed: 29938225 Sci Adv AZD1390 cellular target engagement using phospho-Ser1981 ATM and downstream pathway modulation demonstrating dose-dependent (0 to 300 nM) target engagement (pATM) in LN18 GBM cells at 4-hour time points. Effect of AZD6738 (ATR inhibitor), AZD1775 (Wee1 inhibitor), and AZD2281 (PARP inhibitor, olaparib/Lynparza) selective clinical inhibitors. pChk2; PubMed: 29938225 Sci Adv (F) ATM pathway modulation by AZD1390 in three GBM cell lines indicated. Reduction in IR-induced cell cycle checkpoint (pChk2) by AZD1390 after 6 hours of incubation in the drug, confirmed in three p53 mutant GBM cell lines indicated.	29938225

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].

Protocol

Cell Research:

^[2]

- Collapse

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).

(Only for Reference)

Animal Research:

^[2]

- Collapse

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
(Only for Reference)

References

Solubility (25°C)

In vitro	Ethanol	95 mg/mL (198.92 mM)
	DMSO	14 mg/mL (29.31 mM)
	Water	Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight	477.57
Formula	C₂₇H₃₂FN₅O₂
CAS No.	2089288-03-7
Storage	3 years-20°C powder 2 years-80°C in solvent
Synonyms	N/A
Smiles	CC(C)N1C2=C(C=NC3=CC(=C(C=C32)C4=CN=C(C=C4)OCCCN5CCCCC5)F)N(C1=O)C

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

Dosing volume per animal

Number of animals

Step 2: Enter the in vivo formulation (Different batches have different solubility ratios, please contact Selleck to provide you with the correct ratio)

% DMSO+ % + % Tween 80+ % ddH₂O

Calculate Reset

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 DMSO master liquid, next addμL PEG300， mix and clarify, next addμL Tween 80，mix and clarify, next add μL ddH₂O，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.

Bio Calculators

Molarity Calculator

Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

Mass (mg) = Concentration (mM) × Volume (mL) × Molecular Weight (g/mol)

*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and MSDS / COA (available on product pages).

Dilution Calculator

Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

Concentration _(start) x Volume _(start) = Concentration _(final) x Volume _(final)

This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).

The Serial Dilution Calculator Equation

Serial Dilutions
Concertration (start):
Dilution-folds:

Computed Result

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

Molecular Weight Calculator

Enter the chemical formula of a compound to calculate its molar mass and elemental composition:

Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Molarity Calculator

Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2020-09-01)

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT03423628	Recruiting	Radiation: Radiation Therapy\|Drug: AZD1390	Recurrent Glioblastoma Multiforme\|Primary Glioblastoma Multiforme\|Brain Neoplasms Malignant\|Leptomeningeal Disease (LMD)	AstraZeneca	April 2 2018	Phase 1
NCT03215381	Completed	Drug: [11C]AZD1390	Healthy Volunteer Male Subjects	AstraZeneca\|Karolinska Institutet Quintiles IMS	October 10 2017	Phase 1

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.

ATM/ATR Signaling Pathway Map

Related ATM/ATR Products

Ceralasertib (AZD6738) ^New

Ceralasertib (AZD6738) is an orally active, and selective ATR kinase inhibitor with IC50 of 1 nM. Phase 1/2.
CHIR-99021 (CT99021) ^New

CHIR-99021 (CT99021) is a GSK-3α and GSK-3β inhibitor with IC50 of 10 nM and 6.7 nM, respectively. CHIR99201 does not exhibit cross-reactivity against cyclin-dependent kinases (CDKs) and shows a 350-fold selectivity toward GSK-3β compared to CDKs. CHIR99021 functions as a Wnt/β-catenin activator and induces autophagy.
Dorsomorphin (Compound C) ^New

Dorsomorphin is a potent, reversible, selective AMPK inhibitor with K_i of 109 nM in cell-free assays, exhibiting no significant inhibition of several structurally related kinases including ZAPK, SYK, PKCθ, PKA, and JAK3. Dorsomorphin selectively inhibits the BMP type I receptors ALK2, ALK3 and ALK6. Dorsomorphin is used in promoting specific cell differentiation and inducing cancer cell line autophagy.
KU-55933 (ATM Kinase Inhibitor)

KU-55933 (ATM Kinase Inhibitor) is a potent and specific ATM inhibitor with IC50/K_i of 12.9 nM/2.2 nM in cell-free assays, and is highly selective for ATM as compared to DNA-PK, PI3K/PI4K, ATR and mTOR. KU‑55933 (ATM Kinase Inhibitor) inhibits the activation of autophagy‑initiating kinase ULK1 and results in a significant decrease of autophagy.
VE-821

VE-821 is a potent and selective ATP competitive inhibitor of ATR with K_i/IC50 of 13 nM/26 nM in cell-free assays, shows inhibition of H2AX phosphorylation, minimal activity against PIKKs ATM, DNA-PK, mTOR and PI3Kγ.
KU-60019

KU-60019 is an improved analogue of KU-55933, with IC50 of 6.3 nM for ATM in cell-free assays, 270- and 1600-fold more selective for ATM than DNA-PK and ATR,and is a highly effective radiosensitizer.

Features:Improved analog of KU-55933, and is more effective at blocking ATM-mediated DDR events.
Berzosertib (VE-822)

Berzosertib (VE-822, VX970, M6620) is an ATR inhibitor with IC50 of 19 nM in HT29 cells.

Features:VE-822 is a highly selective and potent derivative of the ATR inhibitor VE-821.
Chloroquine diphosphate

Chloroquine diphosphate is a 4-aminoquinoline anti-malarial and anti-rheumatoid agent, also acting as an ATM activator. Chloroquine is also an inhibitor of toll-like receptors (TLRs).
AZ20

AZ20 is a novel potent and selective inhibitor of ATR kinase with IC50 of 5 nM in a cell-free assay, 8-fold selectivity over mTOR.

Features:AZ20 is the first reported inhibitor of ATR protein kinase demonstrating tumor growth inhibition in vivo.
CP-466722

CP-466722 is a potent and reversible ATM inhibitor, does not affect ATR and inhibits PI3K or PIKK family members in cells.

Choose Your Country or Region

By Signaling Pathways

By product type

AZD1390