AZD-6482

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C22H24N4O4
Molecular Weight	408.4504
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[C@@H](NC1=C(C=CC=C1)C(O)=O)C2=CC(C)=CN3C(=O)C=C(N=C23)N4CCOCC4

InChI

InChIKey=IRTDIKMSKMREGO-OAHLLOKOSA-N

InChI=1S/C22H24N4O4/c1-14-11-17(15(2)23-18-6-4-3-5-16(18)22(28)29)21-24-19(12-20(27)26(21)13-14)25-7-9-30-10-8-25/h3-6,11-13,15,23H,7-10H2,1-2H3,(H,28,29)/t15-/m1/s1

HIDE SMILES / InChI

Description
Sources: https://www.pharmaceutical-networking.com/astra-zeneca-azd6482-for-treatment-of-thrombosis/ | https://www.ncbi.nlm.nih.gov/pubmed/22906130
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/25042253

AZD-6482 is being developed by AstraZeneca to evaluate its therapeutic effects in the treatment of thrombosis. AZD-6482 is essentially a PI3K-beta inhibitor. It is a PI3Kβ inhibitor with IC50 of 10 nM, 8-, 87- and 109-fold more selective to PI3Kβ than PI3Kδ, PI3Kα and PI3Kγ in cell-free assays. by targeting PI3Kβ, AZD-6482 specifically inhibits thrombosis without interfering with normal haemostasis. Therefore, AZD-6482 is used as an anti-thrombotic drug for the prophylaxis of thrombotic disorders. AZD-6482 was in phase I trials by AstraZeneca for the prevention of thrombosis. However, the study was discontinued.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Phosphatidylinositol 3-kinase regulatory subunit beta 1 Target ID: O00459 Gene ID: 5296.0 Gene Symbol: PIK3R2 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/22906130	Inhibitor 8297
PI3-kinase p110-beta subunit 31 Target ID: CHEMBL3145 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25042253 \| https://www.ncbi.nlm.nih.gov/pubmed/22906130	Inhibitor 8297	10.0 nM [IC50]
platelet aggregation 76 Target ID: GO:0070527 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22906130	Inhibitor 8297	0.27 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Thrombosis 22 Sources: https://clinicaltrials.gov/ct2/show/NCT00688714 http://adisinsight.springer.com/drugs/800028400	Preventing		Phase I 428	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461	UGTs 13

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1650	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=137275998	inconclusive [IC50 19.1437 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
UGTs 13	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/25042253/	yes

PubMed

Title	Date	PubMed
Human target validation of phosphoinositide 3-kinase (PI3K)β: effects on platelets and insulin sensitivity, using AZD6482 a novel PI3Kβ inhibitor.	2012 Oct	22906130
Discovery of 9-(1-phenoxyethyl)-2-morpholino-4-oxo-pyrido[1,2-a]pyrimidine-7-carboxamides as oral PI3Kβ inhibitors, useful as antiplatelet agents.	2014 Aug 15	25042253

Patents

Sample Use Guides

In Vivo Use Guide

0,9-364,5 mg administrated through intravenous infusion over 3 hours

Route of Administration: Intravenous

In Vitro Use Guide

AZD-6482 is a potent, selective and ATP competitive PI3Kβ inhibitor (IC(50) 0.01 uM). A maximal anti-platelet effect was achieved at 1 uM in the in vitro. AZD-6482 was more potent in human blood than in dog and rat blood with IC50 values of 0.27, 1.4 and 1.8 uM in human, dog and rat blood, respectively. AZD-6482 concentration-dependently inhibited insulin-induced glucose uptake by human adipocytes in vitro with an IC50 value of 4.4 ±0.8 uM

Name

Type

Language

AZD-6482

Common Name

English

2-(((1R)-1-(7-METHYL-2-(4-MORPHOLINYL)-4-OXO-4H-PYRIDO(1,2-A)PYRIMIDIN-9-YL)ETHYL)AMINO)BENZOIC ACID

Systematic Name

English

AZD6482

Code

English

AZD 6482 [WHO-DD]

Common Name

English

Code System Code Type Description

DRUG BANK

DB14980