AZD6482
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MedKoo CAT#: 406268

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

Description: 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

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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: 408.17976
Molecular Weight: 408.45
Elemental Analysis: C, 64.69; H, 5.92; N, 13.72; O, 15.67

Price and Availability

Size Price Availability Quantity
10.0mg USD 90.0 Same Day
25.0mg USD 150.0 Same Day
50.0mg USD 250.0 Same Day
100.0mg USD 450.0 Same Day
200.0mg USD 750.0 Same Day
500.0mg USD 1650.0 Same Day
1.0g USD 2650.0 Same Day
2.0g USD 4750.0 Same Day
5.0g USD 7950.0 2 Weeks
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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

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/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 58.21 142.51
DMF 10.0 24.48
Ethanol 7.5 18.36

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.

Recalculate based on batch purity %
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: 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.
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.

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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.

AZD6482

10.0mg / USD 90.0


Additional Information

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