AMD3465 hexahydrobromide

製品コードS2879 バッチS287901

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C24H38N6.6HBr
分子量 896.07 CAS No. 185991-07-5
Solubility (25°C)* 体外 Water 98 mg/mL (109.36 mM)
DMSO 2 mg/mL (2.23 mM)
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

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生物活性

製品説明 AMD3465 is a monomacrocyclic CXCR4 antagonist.
in vitro AMD3465 blocks the binding of CXCL12 with IC50 of 18 nM in SupT1 cells. AMD3465 inhibits CXCL12-induced calcium signaling in SupT1 cells with IC50 of 17 nM and also inhibits MAPK phosphorylation. While AMD3465 couldn't block the intracellular calcium fluxes elicited by the CCR5 ligands RANTES, LD78β and MIP-1β in U87.CD4.CCR5 cells. AMD3465 suppresses CXCL12-induced chemotaxis of human T-lymphoid SupT1 cells and prevents chemokine-induced internalization of CXCR4 in U87.CD4 cells. Moreover, AMD3465 proves active against the X4 HIV-1 strains IIIB, NL4.3, RF and HE with IC50 from 6-12 nM. AMD3465 suppresses the HIV-2 strains ROD and EHO with IC50 of 12.3 nM. [1] AMD3465 inhibits SDF-1αligand binding with Ki of 41.7 nM sing the CCRF-CEM cell line. Inhibition of CXCR4 signaling pathways by AMD3465 is demonstrated by inhibition of SDF-1α stimulated calcium flux and GTP binding with IC50 of 12.07 nM and 10.38 nM, respectively. Furthermore AMD3465 is able to inhibit CXCR4-mediated physiological response, cell chemotaxis, with IC50 of 8.7 nM. In addition, AMD3465 has no inhibitory effect on either MIP1α, MCP-1, TARC, RANTES, MIP-3β, or IP10 mediated calcium flux, ligands for CCR1, CCR2b, CCR4, CCR5, CCR7 and CXCR3 respectively, or LTB4 binding to BLT1, thus indicating that AMD3465 is a selective inhibitor of CXCR4 over other chemokine receptors. In a separate study AMD3465 is shown to inhibit SDF-1-mediated CXCR4 internalization in cells expressing GFP-linked CXCR4, and does not cause receptor internalization when incubated with the cells alone. [2]
in vivo The pharmacokinetics of AMD3465 is investigated in mice and dogs. Absorption is rapid following subcutaneous administration. AMD3465 is cleared from dog plasma in a biphasic manner with a terminal half-life of 1.56-4.63 h. AMD3465 shows 100% bioavailability following subcutaneous administration by comparison of exposure to the intravenous and subcutaneous doses. AMD3465 causes leukocytosis when administered subcutaneously in mice and dogs, with peak mobilization occurring between 0.5 h and 1.5 h following subcutaneous dosing in mice and with maximum peak plasma concentration of compound preceding peak mobilization in dogs, indicating that AMD3465 has the potential to mobilize hematopoietic stem cells. [2] AMD3465 abrogates type-2 granuloma formation and eosinophil mobilization at the 6 and 30 mg/kg doses. AMD3465 treatment could cause an ~90% reduction in CXCR4 transcript levels in lungs with type-2 lesions. [3]

プロトコル(参考用のみ)

キナーゼアッセイ Anti-CXCR4 mAb binding assay and flow cytometry
Human T-lymphoid SupT1 cells (0.5 × 106 cells/sample) are washed once with PBS containing 2% FBS and preincubated with AMD3465 at different concentrations for 15 min at room temperature. After centrifugation and washing, the cells are incubated for 30 min on ice with PE-conjugated anti-CXCR4 mAb clone 12G5 in PBS containing 2% FBS. Thereafter, the cells are washed twice with PBS, fixed in 1% paraformaldehyde in PBS and analyzed on a FACS calibur flow cytometer equipped with CellQuest software. As a negative control for aspecific background staining, the cells are stained in parallel with Simultest Isotype Control mAb.
動物実験 動物モデル Male Swiss Webster mice
投薬量 5, 10, 20, 50 and 100 mg/kg
投与方法 Subcutaneous injection

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

CXCR4 Mediates Enhanced Cell Migration in CALM-AF10 Leukemia [ Front Oncol, 2021, 11:708915] PubMed: 35070954

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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