3α-Aminocholestane

An inhibitor of SHP-1

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5mg

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970.00

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10mg

￥1962.00

1570.00

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25mg

￥3887.00

3110.00

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50mg

￥6037.00

4830.00

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100mg

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货号: ajce50360
CAS: 2206-20-4
别名: 3α-氨基胆甾烷
分子式: C27H49N
分子量: 387.68
纯度: >98%
溶解度: Ethanol : 50 mg/mL (128.97 mM);DMSO : < 1 mg/mL (insoluble or slightly soluble)
储存: Store at -20°C
库存: 现货

Background

3α-Aminocholestane is an inhibitor of SH2 domain-containing inositol-5’-phosphatase 1 (SHP-1; IC₅₀ = ~2.5 ?M).¹ It is selective for SHP-1 over SHP-2 and phosphatase and tensin homolog (PTEN; IC₅₀s = >20 ?M). 3α-Aminocholestane induces hyperactivation of the tyrosine kinase SYK in patient-derived Ph⁺ acute lymphoblastic leukemia (ALL) cells and selectively induces cytotoxicity in these cells over mature B cell lymphoma cells. It reduces leukemia burden and increases survival in a tyrosine kinase inhibitor-resistant patient-derived Ph⁺ ALL mouse xenograft model when administered at a dose of 50 mg/kg. 3α-Aminocholestane reduces cell viability of OPM2 multiple myeloma (MM) cells in a concentration-dependent manner and of RPMI8226 MM cells when used at concentrations greater than or equal to 12.5 ?M.² It halts the cell cycle at the G₀/G₁ or G₂/M stages in the highly proliferative OPM2 or less proliferative RPMI8226 cell lines, respectively. It induces apoptosis via activation of caspase-3, caspase-9, and poly(ADP-ribose) polymerase (PARP) in OPM2 cells but not in RPMI8226 cells. 3α-Aminocholestane reduces tumor burden and increases survival in an OPM2 mouse xenograft model.

1.Chen, Z., Shojaee, S., Buchner, M., et al.Signaling threscholds and negative B cell selection in acute lymphoblastic leukemiaNature521(7552)357-361(2015) 2.Fuhler, G.M., Brooks, R., Toms, B., et al.Therapeutic potential of SH2 domain-containing inositol-5'-phosphatase 1 (SHIP1) and SHIP2 inhibition in cancerMol. Med.1865-75(2012)

Protocol

Cell experiment:

Cells are treated in triplicate or more with increasing concentrations of compounds (including 3α-Aminocholestane). Cell viability is determined with a Cell Counting Kit according to the manufacturer’s instructions. The odds density (OD) of compound (including 3α-Aminocholestane )-treated cells is divided by the OD of their vehicle control, and the viability is expressed as a percentage of untreated cells. Results are expressed as mean±standard error of the mean (SEM) of three individual experiments. For phosphatidyl inositol phosphates (PIP) add-back experiments, MCF-7 cells are treated for 2 h with 10 μM SHIP inhibitors (including 3α-Aminocholestane ), after which cells are washed and fresh medium is added. Cells are subsequently cultured in the absence (0 μM) or presence (10 or 20 μM) of either PtdIns(3,4)P2-diC16 (P-3416) or PtdIns(3,5)P2-diC16 (P-3516) for 36 h, after which cell viability is determined by the Cell Counting Kit[2].

Animal experiment:

NOD/SCID/γcIL2R (NSG) mice are injected intraperitoneally with 1×107 OPM2 cells and 6 h later receive an initial injection of 3α-Aminocholestane (3AC) or vehicle. 3α-Aminocholestane is suspended in a 0.3% Klucel/H2O solution at 11.46 mM and administered by intraperitoneal injection of 100 μL solution. Vehicle-treated mice receive 100 μL injection of 0.3% Klucel/H2O solution. The mice are then treated with 3α-Aminocholestane or vehicle daily for the next 6 d and then twice per week in the remaining 15 wks of the survival study[2].

参考文献:

[1]. Chen Z, et al. Signalling thresholds and negative B-cell selection in acute lymphoblastic leukaemia. Nature. 2015 May 21;521(7552):357-61.
[2]. Gwenny M Fuhler, et al. Therapeutic Potential of SH2 Domain-Containing Inositol-5′-Phosphatase 1 (SHIP1) and SHIP2 Inhibition in Cancer. Mol Med. 2012 Feb 10;18:65-75.