azd-8186

Modify Date: 2024-01-02 13:54:26

azd-8186 structure	Common Name	azd-8186
	CAS Number	1627494-13-6	Molecular Weight	457.470
	Density	1.4±0.1 g/cm3	Boiling Point	645.2±55.0 °C at 760 mmHg
	Molecular Formula	C₂₄H₂₅F₂N₃O₄	Melting Point	N/A
	MSDS	N/A	Flash Point	344.0±31.5 °C

Use of azd-8186

AZD8186 is a PI3K inhibitor, which potently inhibits PI3Kβ (IC50=4 nM) and PI3Kδ (IC5050=12 nM) with selectivity over PI3Kα (IC50=35 nM) and PI3Kγ (IC50=675 nM).

Name	azd8186
Synonym	More Synonyms

Description	AZD8186 is a PI3K inhibitor, which potently inhibits PI3Kβ (IC50=4 nM) and PI3Kδ (IC5050=12 nM) with selectivity over PI3Kα (IC50=35 nM) and PI3Kγ (IC50=675 nM).
Related Catalog	Research Areas >> Cancer
Target	PI3Kβ:4 nM (IC50) PI3Kδ:12 nM (IC50) PI3Kα:35 nM (IC50) PI3Kγ:675 nM (IC50)
In Vitro	AZD8186 is a potent inhibitor of PI3Kβ with additional activity versus the PI3Kδ isoform. Tight-binding kinetics of AZD8186 means biochemical assays underestimate the absolute selectivity profile for PI3Ks. In a broad panel of protein and lipid kinase assays selectivity for PI3Kβ and δ is >100-fold versus 74 protein and lipid kinases. At 10 μM, AZD8186 had no significant binding to 442 other kinases in a KinomeScan screen. AZD8186 shows selectivity for PI3K family kinases, no other off-target activity is detected. In the PTEN-null line, MDA-MB-468 AZD8186 inhibits PI3Kβ-dependent activation of pAKT (Ser473) with an IC50 value of 3 nM. Potency in the PIK3CA-mutant line BT474c is 752 nM demonstrating selectivity for PI3Kβ over PI3Kα. IgM mediated stimulation of B cells results in phosphorylation of AKT through activation of PI3Kδ. AZD8186 inhibits IgM-stimulated phosphorylation of pAKT (Ser473) activation in JEKO cells with an IC50 value of 17 nM. In cell proliferation assays, AZD8186 inhibits proliferation of MDA-MB-468 cells with a GI50 value of 65 nM, IgM stimulated JEKO cell growth with an IC50 value of 228 nM. It only inhibited BT474c cell growth with an IC50 value of 1.981 μM consistent with its selectivity for PI3Kβ over PI3Kα[1].
In Vivo	To assess single-agent efficacy of AZD8186 in vivo, antitumor activity is assessed in the PTEN-null TNBC models HCC70 and MDA-MB-468, and the prostate models PC3 and HID28. At 50 and 25 mg/kg twice a day, AZD8186 inhibits the growth of all four models. At 25 and 50 mg/kg, HCC70 is inhibited at 62% (P<0.001) and 85% (P<0.001), respectively, MDA-MB-468 is inhibited at 47% (P<0.001) and 76% (P<0.001), respectively, at end at of study, with regression early in the study. Efficacy in the PTEN-null prostate model, PC3 is less pronounced with 25 and 50 mg/kg giving maximal growth inhibition of 59% (P<0.001) and 64% (P<0.001), respectively. In contrast, AZD8186 gives 79% (P<0.001) growth inhibition in the PTEN-null prostate explant model HID28. In mouse, AZD8186 has a short half-life delivering a PK profile that results in intermittent cover over a 24 hours dosing interval. To increase the time of exposure, animals bearing PC3 tumors are co-dosed with AZD8186 in the presence of the Cyt P450 inhibitor ABT, which results in significantly increased exposure. This also increased the efficacy in the PC3 model with 86% (P<0.005) reduction in tumor growth achieved with 30 mg/kg AZD8186+ABT[1].
Cell Assay	Cells are exposed to AZD8186 at concentrations ranging from 3 to 0.01 μM for 2 hours. Cells are then lysed on ice with a buffer containing 25 mM Tris/HCL pH6.8, 3 mM EDTA, 3 mM EGTA, 50 mM NaF, 2 mM sodium orthovanadate, 270 mM sucrose, 10 mM β-glycerophosphate, 5 mM sodium pyrophosphate, and 0.5% Triton X-100 and protease and phosphatase inhibitors. Lysates are diluted with sample loading buffer, separated on 4% to 12% Bis-Tris Novex gels, transferred onto nitrocellulose membranes, and probed with primary antibodies overnight. After a washing step, membranes are incubated with HRP-tagged secondary antibodies and visualized[1].
Animal Admin	Mice[1] The female CB17 SCID mice ages 6 to 8 weeks are used. HID28 in vivo experiments are performed under contract by Xentech, HID28 tumor fragments (approximately 40 mm3) from donor animals are aseptically implanted subcutaneously in at the level of the interscapular region. Outbred athymic (nu/nu) male mice (HSD: Athymic Nude-Foxn1nu) weighing 18 to 25 g. For all animals studies groups are powered with a minimum of 8 animals per group. AZD8186 is generally formulated once weekly as a suspension in HPMC/Tween and dosed once or twice daily (0 and 6-8 hours). AZD8186 is formulated once weekly either alone in 10% DMSO/60% tri-ethylene glycol (TEG)/30% water for injection (WFI) or in the presence of ABT at 10 mg/mL. For twice daily dosing (0 and 6-8 hours), AZD8186 is co-dosed with ABT at 0 hours and administered alone as the single formulation at 6 to 8 hours. Docetaxel is formulated fresh in physiologic saline at 1.5 mg/mL and dosed as a single i.v. bolus dose at a rate of 0.1 mL/10 g on day 0, 24 hours before the administration of AZD8186.
References	[1]. Hancox U, et al. Inhibition of PI3Kβ signaling with AZD8186 inhibits growth of PTEN-deficient breast and prostate tumors alone and in combination with docetaxel. Mol Cancer Ther. 2015 Jan;14(1):48-58.

Density	1.4±0.1 g/cm3
Boiling Point	645.2±55.0 °C at 760 mmHg
Molecular Formula	C₂₄H₂₅F₂N₃O₄
Molecular Weight	457.470
Flash Point	344.0±31.5 °C
Exact Mass	457.181305
PSA	75.02000
LogP	2.79
Vapour Pressure	0.0±1.9 mmHg at 25°C
Index of Refraction	1.618
Storage condition	-20℃

4H-1-Benzopyran-6-carboxamide, 8-[(1R)-1-[(3,5-difluorophenyl)amino]ethyl]-N,N-dimethyl-2-(4-morpholinyl)-4-oxo-

8-{(1R)-1-[(3,5-Difluorophenyl)amino]ethyl}-N,N-dimethyl-2-(4-morpholinyl)-4-oxo-4H-chromene-6-carboxamide

8-[(1R)-1-[(3,5-Difluorophenyl)amino]ethyl]-N,N-dimethyl-2-(4-morpholinyl)-4-oxo-4H-1-benzopyran-6-carboxamide

Shanghai Nianxing Industrial Co., Ltd
China
Product Name: azd-8186
Price: Click To Check
Purity: 98.0%
Delivery: 10 Day
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Shanghai Jizhi Biochemical Technology Co., Ltd
China
Product Name: azd-8186
Price: ￥11686.0/100mg ￥4256.0/25mg ￥7786.0/50mg ￥926.0/2mg
Purity: 98.0%
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Email: 2130147988@qq.com

ShangHai DC Chemicals Co.,Ltd
China
Product Name: AZD8186
Price: ￥Inquiry/1g
Purity: 98.9%
Delivery: 1 Day
Contact: Tony Lai
Email: order@dcchemicals.com

DC Chemicals Limited
China
Product Name: AZD8186
Price: $500.0/100mg $950.0/250mg $1800.0/1g
Purity: 98.0%
Delivery: 3 Day
Contact: Tony Cao
Email: sales@dcchemicals.com

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