BMS 309403
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
BMS309403是专门设计用于靶向FABP4,Ki值小于2 nM,是一种有效的和选择性的FABP4抑制剂[1]。
脂肪酸结合蛋白(FABPs)是小分子量的疏水蛋白,包含一个大的疏水腔,可接受天然存在的长链脂肪酸和合成的疏水性配体。FABPs充当内源性脂肪酸的转运体,将脂肪酸从细胞表面运送到脂肪酸储存和代谢的不同位点。除了FABP4在调节脂质代谢和胰岛素敏感性方面的作用,最近的药理学和生物学发现表明,FABP4对炎症也具有调节功能。FABP4主要表达于巨噬细胞和炎性反应中[1,2]。
BMS309403是一种芳香联苯三唑化合物,与脂肪酸竞争结合A-FABP的口袋,具有高特异性。BMS309403可降低thp-1巨噬细胞中Mcp-1的分泌[3,4]。
在ApoE-/-小鼠中,BMS309403慢性给药(15 mg/kg/day,12-18周龄时给药)后显著改善松弛。在小鼠中,BMS309403口服给药后以时间和剂量依赖的方式显著增加葡萄糖的吸收。BMS309403可有效保护严重动脉粥样硬化和2型糖尿病[3,4]。
参考文献:
[1]Okada T, Hiromura M, Otsuka M etal. , Synthesis of BMS-309403-related compounds, including [1C]BMS-309403, a radioligand for adipocyte fatty acid binding protein. Chem Pharm Bull (Tokyo). 2012;60(1):164-8.
[2]Suhre K, Rmisch-Margl W, de Angelis MH etal. , Identification of a potential biomarker for FABP4 inhibition: the power of lipidomics in preclinical drug testing. J Biomol Screen. 2011 Jun;16(5):467-75
[3] Lin W1, Huang X, Zhang Letal. , BMS309403 stimulates glucose uptake in myotubes through activation of AMP-activated protein kinase. PLoS One. 2012;7(8):e44570.
[4] Lee MY, Li H, Xiao Y, Zhou Z, Xu A, Vanhoutte PM. Chronic administration of BMS309403 improves endothelial function in apolipoprotein E-deficient mice and in cultured human endothelial cells. Br J Pharmacol. 2011 Apr;162(7):1564-76.
- 1. M.Lamas Bervejilloa, J.Bonanatabc, et al. "A FABP4-PPARγ signaling axis regulates human monocyte responses to electrophilic fatty acid nitroalkenes." Redox Biology. Available online 10 November 2019, 101376.
- 2. Liu G, Wang K, et al. "The natural compound GL22, isolated from Ganoderma mushrooms, suppresses tumor growth by altering lipid metabolism and triggering cell death." Cell Death Dis. 2018 Jun 7;9(6):689. PMID:29880886
- 3. Gao DD, Dou HX, et al. "From hit to lead: Structure-based discovery of naphthalene-1-sulfonamide derivatives as potent and selective inhibitors of fatty acid binding protein 4." Eur J Med Chem. 2018 Jun 25;154:44-59. PMID:29775936
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 474.55 |
Cas No. | 300657-03-8 |
Formula | C31H26N2O3 |
Solubility | insoluble in H2O; ≥18.15 mg/mL in DMSO; ≥48.4 mg/mL in EtOH |
Chemical Name | 2-((2'-(5-ethyl-3,4-diphenyl-1H-pyrazol-1-yl)-[1,1'-biphenyl]-3-yl)oxy)acetic acid |
SDF | Download SDF |
Canonical SMILES | OC(COC1=CC(C2=CC=CC=C2N3N=C(C4=CC=CC=C4)C(C5=CC=CC=C5)=C3CC)=CC=C1)=O |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存,请尽快用完。 |
细胞实验[1]: | |
细胞系 |
αP2+/+ 和αP2-/- THP-1单核细胞白血病细胞系 |
溶解方法 |
该化合物在DMSO中的溶解度大于18.15 mg/mL。若获取更高浓度的溶液,可在37℃下孵育10分钟,随后在超声波浴中摇匀。-20℃以下可储存数月。 |
反应条件 |
1-25 μM |
应用 |
BMS309403以剂量和时间依赖的方式显著降低THP-1巨噬细胞的MCP-1生成。 |
动物实验 [1]: | |
动物模型 |
C57BL/6J背景的雄性Apoe-/- 小鼠 |
给药剂量 |
口服,15 mg/kg/d,六周 |
应用 |
在早期和晚期干预研究中,BMS-309403显著降低近端主动脉的动脉粥样硬化病变面积。 |
注意事项 |
由于实验环境的不同,实际溶解度可能与理论值略有不同,请测试室内所有化合物的溶解度。 |
References: [1]. Furuhashi M, Tuncman G, Grgün C Z, et al. Treatment of diabetes and atherosclerosis by inhibiting fatty-acid-binding protein aP2[J]. Nature, 2007, 447(7147): 959. |
质量控制和MSDS
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