AZD-8186

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C24H25F2N3O4
Molecular Weight	457.4698
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[C@@H](NC1=CC(F)=CC(F)=C1)C2=CC(=CC3=C2OC(=CC3=O)N4CCOCC4)C(=O)N(C)C

InChI

InChIKey=LMJFJIDLEAWOQJ-CQSZACIVSA-N

InChI=1S/C24H25F2N3O4/c1-14(27-18-11-16(25)10-17(26)12-18)19-8-15(24(31)28(2)3)9-20-21(30)13-22(33-23(19)20)29-4-6-32-7-5-29/h8-14,27H,4-7H2,1-3H3/t14-/m1/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25514658 | https://www.ncbi.nlm.nih.gov/pubmed/25220373 | http://adisinsight.springer.com/drugs/800038332

AZD-8186 is a potent and selective inhibitor of PI3Kβ and PI3Kδ with IC50 of 4 nM and 12 nM, respectively. AZD-8186 is currently in phase 1 clinical trials. Combination therapy using AZD-8186 with androgen deprivation results in long-lasting tumor regression, which persisted after treatment cessation.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
PI3-kinase p110-beta subunit 31 Target ID: CHEMBL3145 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25514658 \| https://www.ncbi.nlm.nih.gov/pubmed/25398829	Inhibitor 8297		4.0 nM [IC50]
PI3-kinase p110-delta subunit 43 Target ID: CHEMBL3130 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25514658 \| https://www.ncbi.nlm.nih.gov/pubmed/25398829	Inhibitor 8297		12.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Prostate cancer 178 Sources: http://adisinsight.springer.com/drugs/800038332 https://clinicaltrials.gov/ct2/show/NCT01884285	Primary	Phase I 428	Unknown Approved Use Unknown
Squamous non-small cell lung cancer 2 Sources: http://adisinsight.springer.com/drugs/800038332 https://clinicaltrials.gov/ct2/show/NCT01884285	Primary	Phase I 428	Unknown Approved Use Unknown
Breast cancer 434 Sources: http://adisinsight.springer.com/drugs/800038332 https://clinicaltrials.gov/ct2/show/NCT01884285	Primary	Phase I 428	Unknown Approved Use Unknown
Cancer 592 Sources: https://clinicaltrials.gov/ct2/show/NCT03218826	Primary	Phase I 428	Unknown Approved Use Unknown

AUC

Value	Dose	Co-administered	Analyte	Population
1.2 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25514658	30 μmol/kg single, oral dose: 30 μmol/kg route of administration: Oral experiment type: SINGLE co-administered:		AZD-8186 blood	Mus musculus population: UNKNOWN age: ADULT sex: MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
16% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25514658	30 μmol/kg single, oral dose: 30 μmol/kg route of administration: Oral experiment type: SINGLE co-administered:		AZD-8186 blood	Mus musculus population: UNKNOWN age: ADULT sex: MALE food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY445265	https://www.001chemical.com/chem/search?q=DY445265
1PlusChem LLC	1P001TUR	https://www.1pchem.com/search?query=1P001TUR
AChemBlock	L14957	http://www.achemblock.com/catalogsearch/result/?q=L14957
Angene	AGN-PC-0WAMDF	http://www.angenechemical.com/productshow/AGN-PC-0WAMDF.html
ApexBio Technology	B5950	https://www.apexbt.com/catalogsearch/result/?q=B5950
AstaTech	42556	http://astatechinc.com/CPSResult.php?CRNO=42556
BLD Pharm	BD304663	http://www.bldpharm.com/search/Search.html?keyword=BD304663
Cayman Chemical	17384	http://www.caymanchem.com/app/template/Product.vm/catalog/17384
Chem Scene	CS-4975	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-4975
ChemShuttle	140463	https://www.chemshuttle.com/catalogsearch/result/?q=140463
Combi-Blocks	QW-9195	http://www.combi-blocks.com/cgi-bin/find.cgi?QW-9195
KeyOrganics	AS-74971	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-74971
MedChem Express	HY-12330	https://www.medchemexpress.com/search.html?q=HY-12330&ft=&fa=&fp=
MolPort	MolPort-039-137-739	https://www.molport.com/shop/molecule-link/MolPort-039-137-739
Molcore	MC445265	http://www.molcore.com/CatMC445265.html
Molnova	M12409	https://www.molnova.com/en/serch-list.html?keywords=M12409
MuseChem	I002096	https://www.musechem.com/product/I002096.html
Selleck Chemicals	S7694	http://www.selleckchem.com/search.html?searchDTO.searchParam=S7694
TargetMol	T6773	https://www.targetmol.com/search?keyword=T6773
eMolecules	275095415	https://orderbb.emolecules.com/search/#?query=275095415
eMolecules	302595900	https://orderbb.emolecules.com/search/#?query=302595900
eMolecules	64090032	https://orderbb.emolecules.com/search/#?query=64090032
mcule	MCULE-2350812080	https://mcule.com/MCULE-2350812080/
mcule	MCULE-8172707490	https://mcule.com/MCULE-8172707490/

PubMed

Title	Date	PubMed
Inhibition of PI3Kβ signaling with AZD8186 inhibits growth of PTEN-deficient breast and prostate tumors alone and in combination with docetaxel.	2015 Jan	25398829

Patents

Sample Use Guides

In Vivo Use Guide

In nude mice bearing PTEN-deficient PC3 prostate tumor xenografts, AZD-8186 (100 mg/kg, p.o.) strongly inhibits Akt phosphorylation levels, and causes significant tumor growth inhibition. When used in combination with ABT, AZD8186 (60 mg/kg, p.o.) results in complete inhibition of tumor growth.

Route of Administration: Oral

In Vitro Use Guide

Cells were exposed to AZD-8186 at concentrations ranging from 3 to 0.01 mmol/L for 2 hours. AZD-8186 inhibited PI3Kb-dependent activation of pAKT (Ser473) with an IC50 value of 3 nmol/L. In cell proliferation assays, AZD-8186 inhibited proliferation of MDA-MB-468 cells with a GI50 value of 65 nmol/L, IgM stimulated JEKO cell growth with an IC50 value of 228 nmol/L.

Name

Type

Language

AZD-8186

Common Name

English

AZD8186

Code

English

AZD 8186 [WHO-DD]

Common Name

English

4H-1-BENZOPYRAN-6-CARBOXAMIDE, 8-((1R)-1-((3,5-DIFLUOROPHENYL)AMINO)ETHYL)-N,N-DIMETHYL-2-(4-MORPHOLINYL)-4-OXO-

Systematic Name

English

Code System Code Type Description

DRUG BANK

DB15029