WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H406268
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.
Hodoodo Cat#: H406268
Name: AZD6482
CAS#: 1173900-33-8 (free base)
Chemical Formula: C22H24N4O4
Exact Mass: 408.18
Molecular Weight: 408.450
Elemental Analysis: C, 64.69; H, 5.92; N, 13.72; O, 15.67
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
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 |
Solvent | Max Conc. mg/mL | Max Conc. mM | |
---|---|---|---|
Solubility | |||
DMSO | 58.2 | 142.51 | |
DMF | 10.0 | 24.48 | |
Ethanol | 7.5 | 18.36 |
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: | 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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