Choose Your Country or Region

AZD8186

Catalog No.S7694

For research use only.

AZD8186 is a potent and selective inhibitor of PI3Kβ and PI3Kδ with IC50 of 4 nM and 12 nM, respectively. Phase 1.

CAS No. 1627494-13-6

Selleck's AZD8186 has been cited by 14 publications

Purity & Quality Control

Choose Selective PI3K Inhibitors

Related Compound Libraries

Other PI3K Products

Taselisib (GDC 0032)^New

Taselisib (GDC 0032, RG7604) is a potent, next-generation β isoform-sparing PI3K inhibitor targeting PI3Kα/δ/γ with K_i of 0.29 nM/0.12 nM/0.97nM, >10 fold selective over PI3Kβ.
Pilaralisib (XL147)^New

Pilaralisib (XL147) is a selective and reversible class I PI3K inhibitor for PI3Kα/δ/γ with IC50 of 39 nM/36 nM/23 nM in cell-free assays, less potent to PI3Kβ. Phase 1/2.
LY294002

LY294002 (SF 1101, NSC 697286) is the first synthetic molecule known to inhibit PI3Kα/δ/β with IC50 of 0.5 μM/0.57 μM/0.97 μM, respectively; more stable in solution than Wortmannin, and also blocks autophagosome formation. It not only binds to class I PI3Ks and other PI3K-related kinases, but also to novel targets seemingly unrelated to the PI3K family. LY294002 also inhibits CK2 with IC50 of 98 nM. LY294002 is a non-specific DNA-PKcs inhibitor and activates autophagy and apoptosis.
3-Methyladenine (3-MA)

3-Methyladenine (3-MA, NSC 66389) is a selective PI3K inhibitor for Vps34 and PI3Kγ with IC50 of 25 μM and 60 μM in HeLa cells; blocks class I PI3K consistently, whereas suppression of class III PI3K is transient, and also blocks autophagosome formation. 3-Methyladenine (3-MA) is successfully used to suppress mitophagy. Solutions of 3-MA are best fresh-prepared by heating.
Idelalisib

Idelalisib (CAL-101, GS-1101) is a selective p110δ inhibitor with IC50 of 2.5 nM in cell-free assays; shown to have 40- to 300-fold greater selectivity for p110δ than p110α/β/γ, and 400- to 4000-fold more selectivity to p110δ than C2β, hVPS34, DNA-PK and mTOR. Idelalisib also stimulates autophagy.
Wortmannin (KY 12420)

Wortmannin (KY 12420, SL-2052, BRN 0067676, NSC 627609) is the first described PI3K inhibitor with IC50 of 3 nM in a cell-free assay, with little selectivity within the PI3K family. Wortmannin blocks autophagosome formation and potently inhibits DNA-PK/ATM with IC50 of 16 nM and 150 nM in cell-free assays. Wortmannin also inhibits PLK1 activity.
Dactolisib (BEZ235)

Dactolisib (BEZ235, NVP-BEZ235) is a dual ATP-competitive PI3K and mTOR inhibitor for p110α/γ/δ/β and mTOR(p70S6K) with IC50 of 4 nM /5 nM /7 nM /75 nM /6 nM in cell-free assays, respectively. Inhibits ATR with IC50 of 21 nM in 3T3^TopBP1-ER cell. Dactolisib induces autophagy and suppresses HIV-1 replication. Phase 2.
Buparlisib (BKM120)

Buparlisib (BKM120, NVP-BKM120) is a selective PI3K inhibitor of p110α/β/δ/γ with IC50 of 52 nM/166 nM/116 nM/262 nM in cell-free assays, respectively. Reduced potency against VPS34, mTOR, DNAPK, with little activity to PI4Kβ. Buparlisib induces apoptosis. Phase 2.
Pictilisib (GDC-0941)

Pictilisib (GDC-0941, RG7321) is a potent inhibitor of PI3Kα/δ with IC50 of 3 nM in cell-free assays, with modest selectivity against p110β (11-fold) and p110γ (25-fold). Pictilisib (GDC-0941) induces autophagy and apoptosis. Phase 2.

Download Inhibitor Catalog

PI3K Signaling Pathway Map

Biological Activity

Description

AZD8186 is a potent and selective inhibitor of PI3Kβ and PI3Kδ with IC50 of 4 nM and 12 nM, respectively. Phase 1.

Targets

PI3Kβ ^[1] (Cell-free assay)	PI3Kδ ^[1] (Cell-free assay)	PI3Kα ^[1] (Cell-free assay)
4 nM	12 nM	35 nM

In vitro

AZD8186 potently inhibits p-Akt in MDA-MB-468 cells sensitive to PI3Kβ inhibition and Jeko B cells sensitive to PI3Kδ inhibition with IC50 of 3 nM and 4 nM, respectively. ^[1] AZD8186 shows preferred growth inhibition activity in most PTEN deficient cell lines with GI50 of <1 μM. ^[2]

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Formulation	Activity Description	PMID

MDA-MB-468	NILpcGlHfW6ldHnvckBie3OjeR?=		MXSyJIhzew>?	M{\WS2lvcGmkaYTpc44hd2ZiUFmzT4JmfGFiaX6gVHRGVi2wdXzsJIh2dWGwIF3ERU1OSi12NkigZ4VtdHNiYYPz[ZN{\WRiYYOgbY5pcWKrdHnvckBw\iCDa4SgdIhwe3Cqb4L5cIF1cW:wIHHmeIVzKDJiaILzMEBKSzVyPUCuNFA{\|ryP	M{HkbVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3NUG0OlU5Lz5{NUWxOFY2QDxxYU6=
Jeko B	MnnRSpVv[3Srb36gZZN{[Xl?		NWXSR3ZEOiCqcoO=	M1jIbmlvcGmkaYTpc44hd2ZiUFmzT4RmdHSjIHnuJIh2dWGwIFrlb48hSiClZXzsd{Bie3Onc4Pl[EBieyCrbnjpZol1cW:wIH;mJGFsfCCyaH;zdIhwenmuYYTpc44h[W[2ZYKgNkBpenNuIFnDOVA:OC5yMUhOwG0>	M{L0dlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3NUG0OlU5Lz5{NUWxOFY2QDxxYU6=
BT474	NWHtfYp6TnWwY4Tpc44h[XO\|YYm=		MomwNkBpenN?	MmOxTY5pcWKrdHnvckBw\iCSSUPLZYxxcGFibYX0ZY51KGi3bXHuJGJVPDd2IHPlcIx{KGG\|c3Xzd4VlKGG\|IHnubIljcXSrb36gc4YhSWu2IIDoc5NxcG:{eXzheIlwdiCjdDDUfZIuOzB6IHHmeIVzKDJiaILzMEBKSzVyPUCuO\|Uz\|ryP	NWLuXmNtRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW1NVQ3PThpPkK1OVE1PjV6PD;hQi=>
PC3	NHmwbGdHfW6ldHnvckBie3OjeR?=	MVSxNFAhdWdxa3e=		MV3Jcohq[mm2aX;uJI9nKEGtdDDwbI9{eGixconsZZRqd25iYYSgV4VzPDd\|IHnuJHBVTU5vZHXmbYNq\W62IHj1cYFvKFCFMzDj[YxteyC6ZX7v[5Ji\nRibX;1d4UhdW:mZXygZZQhOTByIH3nM4toNCCybzDzbY5odGViZH;z[UBu\WG\|dYLl[EB2eCC2bzC4JIhzew>?	NH;MS2E9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUWxOFY2QCd-MkW1NVQ3PTh:L3G+
PC3	NVP2[2ZqSW62aYT1cY9zKGG\|c3H5	M3vPNFMxKG2pL3vn		NGqye\|VCdnSrdIXtc5Ih[WO2aY\peJkh[WejaX7zeEBpfW2jbjDQR\|Mh[2WubIOgfIVvd2e{YX\0JI1wfXOnIH3v[IVtKGG\|c3Xzd4VlKGG\|IHnubIljcXSrb36gc4YhfHWvb4Kg[5Jwf3SqIHH0JFMxKG2pL3vnMEBxdyCkaXSgbY4heHKnc3XuZ4Uhd2ZiMT3hcYlvd2KnborveJJq[XqxbHW=	NEe4WYo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUWxOFY2QCd-MkW1NVQ3PTh:L3G+
PC3	NETqNIVCdnSrdIXtc5Ih[XO\|YYm=	NHPiemw3OCCvZz;r[y=>		NH\TToRCdnSrdIXtc5Ih[WO2aY\peJkh[WejaX7zeEBpfW2jbjDQR\|Mh[2WubIOgfIVvd2e{YX\0JI1wfXOnIH3v[IVtKGG\|c3Xzd4VlKGG\|IHnubIljcXSrb36gc4YhfHWvb4Kg[5Jwf3SqIHH0JFYxKG2pL3vnMEBxdyCkaXSgbY4heHKnc3XuZ4Uhd2ZiMT3hcYlvd2KnborveJJq[XqxbHW=	Ml\3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV3MUS2OVgoRjJ3NUG0OlU5RC:jPh?=

Click to View More Cell Line Experimental Data

In vivo

In nude mice bearing PTEN-deficient PC3 prostate tumor xenografts, AZD8186 (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. ^[1] In the mouse PTEN-null TNBC models HCC70 and MDA-MB-468, and the prostate models HID28, AZD8186 (50 mg/kg, p.o.) also inhibits the growth of tumors. ^[2] Combination therapy using AZD8186 with androgen deprivation results in long-lasting tumor regression, which persisted after treatment cessation. ^[3]

Protocol (from reference)

Kinase Assay:^[1]	PI3Kα, PI3Kβ, PI3Kγ and PI3Kδ enzyme assays: The inhibition of PI3Kα, PI3Kβ, PI3Kγ and PI3Kδ human recombinant PI3K isoforms is evaluated using a Kinase-Glo Plus Assay Kit. 12 point half-log concentration-response curves with a top concentration of 100 μM are constructed by dispensing DMSO solubilised compounds into white 384-well medium-binding microplates using an Echo 555. 3 μL of the appropriate PI3K in Tris buffer (50 mM Tris pH7.4, 0.05% CHAPS, 2.1 mM DTT, and 10 mM MgCl₂) is added. The plate is covered and allowed to pre-incubate with compound for 20 minutes prior to addition of 3 μL of substrate solution containing PIP2 and ATP. The enzyme reaction is stopped after 80 minutes by the addition of Kinase Glo detection solution. Plates are covered and incubated for 30 minutes at room temperature before the luminescence signal is read using a PHERAstar plate reader. The final concentrations of DMSO, ATP and PIP2 in the assay are 2%, 8 μM, and 80 μM respectively. The final concentrations of PI3Kα, PI3Kβ, PI3Kγ and PI3Kδ are respectively 20 nM, 20 nM, 45 nM and 30 nM. For PI3Kα, PI3Kβ and PI3Kδ the concentration of active enzyme is determined as outlined in the enzyme assay tight binding limit determination section. For PI3Kγ the concentration of enzyme is determined by Bradford assay. IC50 values are calculated using Genedata Screener.
Cell Research:^[2]	Cell lines: A subset of cancer cell lines Concentrations: ~30 μM Incubation Time: 72 hours Method: Cells are seeded in 96-well plates, at a density to allow for logarithmic growth during the 72 hour assay, and incubated overnight at 37°C, 5% CO₂. Cells are treated with AZD8186 (30 to 0.003 μM) for 72 hours and cell proliferation measured by MTS. The CellTiter Aqueous Non-Radioactive Cell Proliferation Assay reagent is used in accordance with the manufacturer’s protocol and Absorbance measured with Tecan Ultra instrument. Pre-dose measurements are made and the concentration needed to reduce the growth of treated cells to half that of untreated cells (GI50) values are determined.
Animal Research:^[1]	Animal Models: Nude mice bearing PTEN-deficient PC3 prostate tumor xenografts Dosages: 100 mg/kg b.i.d Administration: p.o.

References	[1] Barlaam B, et al. J Med Chem. 2015, 58(2), 943-962. [2] Hancox U, et al. Mol Cancer Ther. 2015, 14(1), 48-58. [3] Marques RB, et al. Eur Urol. 2015, 67(6), 1177-1185.

References

Solubility (25°C)

In vitro


In vivo	Add solvents to the product individually and in order (Data is from Selleck tests instead of citations): 10% DMSO + 60% TEG+ 30% WFI For best results, use promptly after mixing.	16mg/mL

Chemical Information

Molecular Weight	457.47
Formula	C₂₄H₂₅F₂N₃O₄
CAS No.	1627494-13-6
Storage	3 years	-20°C	powder
Storage	2 years	-80°C	in solvent
Smiles	CC(C1=CC(=CC2=C1OC(=CC2=O)N3CCOCC3)C(=O)N(C)C)NC4=CC(=CC(=C4)F)F

Download AZD8186 SDF

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.

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

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.

* Indicates a Required Field

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):