AZD6482 | AZD-6482 | CAS#1173900-33-8 | PI3K inhibitor | 1173900-37-2

MedKoo Cat#: 406268 | Name: AZD6482

Description:

WARNING: This product is for research use only, not for human or veterinary use.

AZD6482 is a potent, selective and ATP competitive PI3Kβ inhibitor (IC(50) 0.01 μm). AZD6482 inhibited insulin-induced human adipocyte glucose uptake in vitro (IC(50) of 4.4 μm). This is the first human target validation for PI3Kβ inhibition as anti-platelet therapy showing a mild and generalized antiplatelet effect attenuating but not completely inhibiting multiple signaling pathways with an impressive separation towards primary hemostasis. AZD6482 at 'supratherapeutic' plasma concentrations may attenuate insulin signaling, most likely through PI3Kα inhibition.

Chemical Structure

AZD6482

CAS#1173900-33-8 (free base)

Theoretical Analysis

MedKoo Cat#: 406268

Name: AZD6482

CAS#: 1173900-33-8 (free base)

Chemical Formula: C22H24N4O4

Exact Mass: 408.1798

Molecular Weight: 408.45

Elemental Analysis: C, 64.69; H, 5.92; N, 13.72; O, 15.67

Price and Availability

Size	Price	Availability
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,250.00	Ready to ship
500mg	USD 2,650.00	Ready to ship
1g	USD 3,750.00	Ready to ship

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Related CAS #

1173900-33-8 (free base) 1173900-37-2 (S-isomer)

Synonym

AZD6482; AZD-6482; AZD 6482.

IUPAC/Chemical Name

(R)-2-((1-(7-methyl-2-morpholino-4-oxo-4H-pyrido[1,2-a]pyrimidin-9-yl)ethyl)amino)benzoic acid

InChi Key

IRTDIKMSKMREGO-OAHLLOKOSA-N

InChi Code

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

SMILES Code

O=C(O)C1=CC=CC=C1N[C@@H](C2=CC(C)=CN(C2=NC(N3CCOCC3)=C4)C4=O)C

Appearance

white solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Note: AZD-6438-S-isomer has CAS#1173900-37-2

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#SSC30819

QC Data

View QC data: current batch, Lot#SSC30819

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

AZD 6482 (KIN-193) is a p110β inhibitor with an IC50 of 0.69 nM.

In vitro activity:

The effect of the PI3Kβ inhibitor AZD6482 on glioma cells was investigated. The CCK-8 assay showed dose-dependent cytotoxicity in glioma cell lines treated with AZD6482. Additionally, AZD6482 treatment was found to significantly induce apoptosis and cell cycle arrest as detected using flow cytometry. Moreover, as shown using western blot analysis, the levels of p-AKT, p-GSK-3β, Bcl-2, and cyclin D1 were decreased after AZD6482 treatment. In addition, AZD6482 inhibited the migration and invasion of glioma cells as detected by wound healing and Transwell invasion assays. These findings indicate that AZD6482 exerts an antitumour effect by inhibiting proliferation and inducing apoptosis in human glioma cells. Reference: Oncol Rep. 2019 Jan;41(1):125-132. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6278584/

In vivo activity:

To evaluate the combination effect of PI3Kβ and MLK3 inhibitors in vivo, Balb/C nude mice bearing subcutaneous U-118 MG glioblastoma xenograft were intraperitoneally injected with vehicle, AZD6482 (30 mg/kg), URMC-099 (3 mg/kg), and the combination of AZD6482 (30 mg/kg) and URMC-099 (3 mg/kg), respectively. Neither AZD6482 nor URMC-099 alone significantly suppressed U-118 MG xenograft tumor growth. However, compared with single inhibitor alone, combination of AZD6482 and URMC-099 effectively decreased tumor volume after 26-day post-administration (p < 0.05). Tumor weight and size were also reduced by the combination of AZD6482 and URMC-099 after sacrifice in 36-day post-administration (p < 0.05) (Fig. 6a, b). Reference: Cancer Cell Int. 2021 Jan 6;21(1):24. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789614/

	Solvent	mg/mL	mM
Solubility
	DMSO	58.2	142.51
	DMF	10.0	24.48
	Ethanol	7.5	18.36

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 408.45 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Xu PF, Yang JA, Liu JH, Yang X, Liao JM, Yuan FE, Liu BH, Chen QX. PI3Kβ inhibitor AZD6482 exerts antiproliferative activity and induces apoptosis in human glioblastoma cells. Oncol Rep. 2019 Jan;41(1):125-132. doi: 10.3892/or.2018.6845. Epub 2018 Nov 2. PMID: 30542720; PMCID: PMC6278584. 2. Zhao HF, Wu CP, Zhou XM, Diao PY, Xu YW, Liu J, Wang J, Huang XJ, Liu WL, Chen ZP, Huang GD, Li WP. Synergism between the phosphatidylinositol 3-kinase p110β isoform inhibitor AZD6482 and the mixed lineage kinase 3 inhibitor URMC-099 on the blockade of glioblastoma cell motility and focal adhesion formation. Cancer Cell Int. 2021 Jan 6;21(1):24. doi: 10.1186/s12935-020-01728-4. PMID: 33407478; PMCID: PMC7789614.

In vitro protocol:

In vivo protocol:

1. Zhao HF, Wu CP, Zhou XM, Diao PY, Xu YW, Liu J, Wang J, Huang XJ, Liu WL, Chen ZP, Huang GD, Li WP. Synergism between the phosphatidylinositol 3-kinase p110β isoform inhibitor AZD6482 and the mixed lineage kinase 3 inhibitor URMC-099 on the blockade of glioblastoma cell motility and focal adhesion formation. Cancer Cell Int. 2021 Jan 6;21(1):24. doi: 10.1186/s12935-020-01728-4. PMID: 33407478; PMCID: PMC7789614.

1: Wang J, Wen J, Yi R, Liu F, Zhou J, Liu G, Li Q, Yang Z, Su X. High selectivity of PI3Kβ inhibitors in SETD2-mutated renal clear cell carcinoma. J BUON. 2015 Sep-Oct;20(5):1267-75. PubMed PMID: 26537074. 2: Nylander S, Wågberg F, Andersson M, Skärby T, Gustafsson D. Exploration of efficacy and bleeding with combined phosphoinositide 3-kinase β inhibition and aspirin in man. J Thromb Haemost. 2015 Aug;13(8):1494-502. doi: 10.1111/jth.13027. Epub 2015 Jul 23. PubMed PMID: 26096765. 3: Cescon DW, Gorrini C, Mak TW. Breaking up is hard to do: PI3K isoforms on the rebound. Cancer Cell. 2015 Jan 12;27(1):5-7. doi: 10.1016/j.ccell.2014.12.003. PubMed PMID: 25584888. 4: Costa C, Ebi H, Martini M, Beausoleil SA, Faber AC, Jakubik CT, Huang A, Wang Y, Nishtala M, Hall B, Rikova K, Zhao J, Hirsch E, Benes CH, Engelman JA. Measurement of PIP3 levels reveals an unexpected role for p110β in early adaptive responses to p110α-specific inhibitors in luminal breast cancer. Cancer Cell. 2015 Jan 12;27(1):97-108. doi: 10.1016/j.ccell.2014.11.007. Epub 2014 Dec 24. PubMed PMID: 25544637; PubMed Central PMCID: PMC4745884. 5: Nichols AC, Black M, Yoo J, Pinto N, Fernandes A, Haibe-Kains B, Boutros PC, Barrett JW. Exploiting high-throughput cell line drug screening studies to identify candidate therapeutic agents in head and neck cancer. BMC Pharmacol Toxicol. 2014 Nov 27;15:66. doi: 10.1186/2050-6511-15-66. PubMed PMID: 25428177; PubMed Central PMCID: PMC4258049. 6: Laurent PA, Séverin S, Hechler B, Vanhaesebroeck B, Payrastre B, Gratacap MP. Platelet PI3Kβ and GSK3 regulate thrombus stability at a high shear rate. Blood. 2015 Jan 29;125(5):881-8. doi: 10.1182/blood-2014-07-588335. Epub 2014 Nov 14. PubMed PMID: 25398937. 7: Giordanetto F, Barlaam B, Berglund S, Edman K, Karlsson O, Lindberg J, Nylander S, Inghardt T. Discovery of 9-(1-phenoxyethyl)-2-morpholino-4-oxo-pyrido[1,2-a]pyrimidine-7-carboxamides as oral PI3Kβ inhibitors, useful as antiplatelet agents. Bioorg Med Chem Lett. 2014 Aug 15;24(16):3936-43. doi: 10.1016/j.bmcl.2014.07.007. Epub 2014 Jul 9. PubMed PMID: 25042253. 8: Weigelt B, Warne PH, Lambros MB, Reis-Filho JS, Downward J. PI3K pathway dependencies in endometrioid endometrial cancer cell lines. Clin Cancer Res. 2013 Jul 1;19(13):3533-44. doi: 10.1158/1078-0432.CCR-12-3815. Epub 2013 May 14. PubMed PMID: 23674493; PubMed Central PMCID: PMC3700760. 9: Jackson SP, Schoenwaelder SM. Antithrombotic phosphoinositide 3-kinase β inhibitors in humans: a 'shear' delight! J Thromb Haemost. 2012 Oct;10(10):2123-6. doi: 10.1111/j.1538-7836.2012.04912.x. PubMed PMID: 22943292. 10: Nylander S, Kull B, Björkman JA, Ulvinge JC, Oakes N, Emanuelsson BM, Andersson M, Skärby T, Inghardt T, Fjellström O, Gustafsson D. Human target validation of phosphoinositide 3-kinase (PI3K)β: effects on platelets and insulin sensitivity, using AZD6482 a novel PI3Kβ inhibitor. J Thromb Haemost. 2012 Oct;10(10):2127-36. doi: 10.1111/j.1538-7836.2012.04898.x. PubMed PMID: 22906130.