BC1618
目录号 : GC62135
An inhibitor of FBXO48
Cas No.:2222094-18-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
BC-1618 is an inhibitor of F-box only protein 48 (FBXO48), an E3 ubiquitin ligase.1 It is selective for FBXO48 over FBXO30 at 3 ?M. BC-1618 (0.5-10 ?M) increases the levels of phosphorylated AMP-activated protein kinase (pAMPK) and phosphorylated acetyl-CoA carboxylase (pACC), an AMPK downstream substrate, in HEK293T cells expressing human FBXO48. It induces mitochondrial fission in BEAS-2B cells and autophagy in HEK293A cells expressing GFP-tagged LC3. BC-1618 also inhibits LPS-induced activation of NF-κB in THP-1 cells in a reporter assay and cytokine release in isolated human peripheral blood mononuclear cells (PBMCs). It increases insulin sensitivity in a mouse model of high-fat diet-induced obesity when administered at a dose of 20 mg/kg.
1.Liu, Y., Jurczak, M.J., Lear, T.B., et al.A Fbxo48 inhibitor prevents pAMPKα degradation and ameliorates insulin resistanceNat. Chem. Biol.17(3)298-306(2021)
| Cas No. | 2222094-18-8 | SDF | |
| 分子式 | C24H24F3NO2 | 分子量 | 415.45 |
| 溶解度 | DMSO : 100 mg/mL (240.70 mM; Need ultrasonic)|Water : < 0.1 mg/mL (insoluble) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.407 mL | 12.0351 mL | 24.0703 mL |
| 5 mM | 0.4814 mL | 2.407 mL | 4.8141 mL |
| 10 mM | 0.2407 mL | 1.2035 mL | 2.407 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
A Fbxo48 inhibitor prevents pAMPKα degradation and ameliorates insulin resistance
Nat Chem Biol 2021 Mar;17(3):298-306.PMID:33495648DOI:10.1038/s41589-020-00723-0.
The adenosine monophosphate (AMP)-activated protein kinase (Ampk) is a central regulator of metabolic pathways, and increasing Ampk activity has been considered to be an attractive therapeutic target. Here, we have identified an orphan ubiquitin E3 ligase subunit protein, Fbxo48, that targets the active, phosphorylated Ampkα (pAmpkα) for polyubiquitylation and proteasomal degradation. We have generated a novel Fbxo48 inhibitory compound, BC1618, whose potency in stimulating Ampk-dependent signaling greatly exceeds 5-aminoimidazole-4-carboxamide-1-β-ribofuranoside (AICAR) or metformin. This compound increases the biological activity of Ampk not by stimulating the activation of Ampk, but rather by preventing activated pAmpkα from Fbxo48-mediated degradation. We demonstrate that, consistent with augmenting Ampk activity, BC1618 promotes mitochondrial fission, facilitates autophagy and improves hepatic insulin sensitivity in high-fat-diet-induced obese mice. Hence, we provide a unique bioactive compound that inhibits pAmpkα disposal. Together, these results define a new pathway regulating Ampk biological activity and demonstrate the potential utility of modulating this pathway for therapeutic benefit.
Modulation of tumor growth by allogeneic blood transfusion
J Cancer Res Clin Oncol 1986;111(1):50-3.PMID:3949850DOI:10.1007/BF00402776.
The effect of a single blood transfusion on the formation and outgrowth of experimental lung metastases was assessed in two tumor models in rats. The transfusions were given either 1 week before (day -7) or 1 week after (day +7) tumor cell inoculation. The first approach was performed to investigate the effect of transfusions on the formation of lung colonies, the second approach to study the effect on the outgrowth of established metastases. The first tumor model used was a transplantable, nonimmunogenic sarcoma (LS175) in BN rats. Animals were injected i.v. with 10(5) tumor cells and the number of metastases developing in the lungs was counted after 18 days. Experimental animals received 1 ml of allogeneic WAG blood, controls were given 1 ml of syngeneic BN blood. A single allogeneic transfusion given on day -7 had no effect on the formation of LS175 lung colonies but, when given day +7, stimulated the outgrowth of established metastases. The second tumor model was a highly immunogenic transplantable basal cell carcinoma (BC1618) in inbred WAG rats. Rats were injected i.v. with 10(6) tumor cells and the numbers of lung colonies were counted after 21 days. Experimental animals were transfused with 1 ml of BN blood, controls received 1 ml of WAG blood. An allogeneic transfusion on day -7 led to a significant inhibition of lung metastases, whereas a transfusion on day +7 had no effect. The results clearly indicate that allogeneic blood transfusions can modulate tumor growth and metastasis. Although immunological factors seem to play a crucial role in this transfusion phenomenon, there was no clear-cut correlation between the observed effects (accelerated tumor growth vs inhibition of metastasis) and the type of immunomodulation evoked.