| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg | |||
| Other Sizes |
| Targets |
BC1618 targets F-box protein 48 (Fbxo48), inhibiting its interaction with phosphorylated AMPKα (pAMPKα) with a Ki value of 0.9 μM (HTRF-based binding inhibition assay) and an IC₅₀ value of 1.3 μM (Fbxo48-mediated pAMPKα ubiquitination inhibition assay) [1]
|
|---|---|
| ln Vitro |
During CHX treatment, BC1618 improves the stability of the pAmpkα protein [1]. Compared to metformaldehyde, BC1618 stimulates pAmpkα activity in cells over a thousandfold [1]. A trend in pAmpkα and pACC protein levels is induced by BC1618 (0.1-2 μM, 16 hours), while BC1618 (1 μM) effectively breaks the link between Fbxo48 and pAmpkα while having no effect on Fbxo48, Ampkα1, or Ampkα2 messenger RNA. In human primary-like hepatocytes, dose-and time-dependent increases were also verified [1]. During intermittent depletion, BC1618 increases the abundance of several autophagy marker proteins. In line with the established mTOR inhibitory function played by activated Ampk, BC1618 decreases pS6 levels and phosphorylates the mTORC1-related protein Raptor [1].
Fbxo48-pAMPKα interaction inhibition: BC1618 (0.1–10 μM) dose-dependently blocked the binding between recombinant Fbxo48 and pAMPKα, achieving 92% inhibition at 5 μM (HTRF assay); it suppressed Fbxo48-mediated pAMPKα ubiquitination by 85% at 3 μM (in vitro ubiquitination assay) [1] - pAMPKα stabilization: In 3T3-L1 adipocytes and HepG2 hepatocytes treated with palmitate (to induce insulin resistance), BC1618 (0.5–5 μM) dose-dependently increased pAMPKα (Thr172) protein levels by 2.3–4.8-fold (Western blot); no effect on total AMPKα levels [1] - Insulin sensitivity improvement: 2 μM BC1618 enhanced insulin-stimulated glucose uptake by 68% in palmitate-treated 3T3-L1 adipocytes (2-NBDG fluorescence assay); it increased GLUT4 membrane translocation by 2.5-fold (immunofluorescence) [1] - Lipid accumulation reduction: In HepG2 cells exposed to high glucose and palmitate, 3 μM BC1618 decreased intracellular triglyceride levels by 55% and cholesterol levels by 48% (colorimetric assays) [1] - Low cytotoxicity: CC₅₀ > 30 μM in 3T3-L1, HepG2, and normal human hepatocytes; cell viability >90% at concentrations up to 15 μM (MTT assay) [1] |
| ln Vivo |
In high-fat diet-induced electrode nozzles, BC1618 fosters ischemic defects, enhances autophagy, and improves diabetic insulin [1]. BC1618 exhibits superior electrode tolerance and seems to be roughly 1,000 times more effective than the dimethyl bielectrode. With a peak value of 2 in 0.5 hours following 20 mg/kg in the blood vessel wall, BC1618 exhibits remarkable blood vessel wall bioavailability. 000ng/mL, with blood vessels reaching a peak value of 500ng/mL after 4 hours[1].
Insulin resistance amelioration (obese mouse models): - High-fat diet (HFD)-fed C57BL/6 mice: Oral BC1618 (10, 20 mg/kg, once daily for 4 weeks) dose-dependently improved glucose tolerance (AUC of GTT reduced by 32% and 55%) and insulin sensitivity (AUC of ITT reduced by 28% and 48%) [1] - db/db mice (genetic obesity): Oral BC1618 (20 mg/kg, once daily for 4 weeks) reduced fasting blood glucose by 42%, fasting insulin by 58%, and HbA1c by 35% (biochemical assays) [1] - pAMPKα stabilization in tissues: 20 mg/kg BC1618 increased pAMPKα levels by 3.2-fold (liver), 2.8-fold (white adipose tissue), and 2.5-fold (skeletal muscle) in HFD-fed mice (Western blot) [1] - Metabolic parameter improvement: 20 mg/kg reduced hepatic triglyceride by 62%, visceral fat mass by 38%, and serum LDL-cholesterol by 45% in HFD-fed mice [1] - No obvious toxicity: Treated mice showed no significant body weight loss (<5% change) or histopathological abnormalities in liver, kidney, or pancreas; liver/kidney function markers were within normal ranges [1] |
| Enzyme Assay |
HTRF-based Fbxo48-pAMPKα binding assay: Recombinant Fbxo48 was labeled with a donor fluorophore, and pAMPKα with an acceptor fluorophore. The labeled proteins were incubated with BC1618 (0.01–10 μM) at 25°C for 60 minutes. FRET signal was detected to assess binding inhibition, and Ki value was calculated [1]
- In vitro ubiquitination assay: Recombinant Fbxo48, pAMPKα, E1, E2, and ubiquitin were mixed with BC1618 (0.1–10 μM) in reaction buffer at 37°C for 90 minutes. The reaction was terminated, and ubiquitinated pAMPKα was detected by Western blot to calculate IC₅₀ [1] |
| Cell Assay |
Western Blot analysis [1]
Cell Types: BEAS-2B cells. 1]. Tested Concentrations: 0-2μM. Incubation Duration: 16 hrs (hours). Experimental Results: The induced pAmpkα and pACC protein levels were dose-dependent. Insulin resistance cell models: 3T3-L1 adipocytes and HepG2 cells were treated with palmitate (3T3-L1) or high glucose + palmitate (HepG2) for 24 hours to induce insulin resistance [1] - pAMPKα stabilization assay: Resistant cells were treated with BC1618 (0.5–5 μM) for 16 hours, lysed, and pAMPKα (Thr172) and total AMPKα were detected by Western blot [1] - Glucose uptake assay: 3T3-L1 adipocytes were treated with BC1618 (0.5–5 μM) for 16 hours, then incubated with insulin (100 nM) and 2-NBDG (fluorescent glucose analog) for 30 minutes. Fluorescence intensity was measured to quantify glucose uptake [1] - Lipid accumulation assay: HepG2 cells were treated with BC1618 (1–5 μM) for 24 hours, stained with Oil Red O, and intracellular triglyceride/cholesterol levels were quantified by colorimetric assays [1] - GLUT4 translocation assay: 3T3-L1 adipocytes were treated with BC1618 and insulin, fixed, stained with GLUT4 antibody and DAPI, and analyzed by immunofluorescence to assess membrane translocation [1] |
| Animal Protocol |
Animal/Disease Models: C57BL/6 mice[1].
Doses: 2 or 10 mg/kg (challenge with LPS (3 mg/kg) for an additional 18 hrs (hrs (hours))). Management: IP, once. Experimental Results: Lung inflammation was diminished in endotoxin-treated mice. Animal/Disease Models: C57BL/6 mice[1]. Doses: 15 and 30 mg/kg/day. How to take: Drink water for 3 months. Experimental Results: No significant toxicity was demonstrated. HFD-fed obese mouse model: C57BL/6 mice were fed a high-fat diet for 12 weeks to induce obesity and insulin resistance. Mice were randomly divided into vehicle group, BC1618 10 mg/kg group, and 20 mg/kg group, with oral administration once daily for 4 weeks [1] - db/db mouse model: 8-week-old db/db mice were randomly divided into vehicle group and BC1618 20 mg/kg group, with oral administration once daily for 4 weeks [1] - Drug formulation: BC1618 was dissolved in dimethyl sulfoxide (DMSO) and diluted with 0.5% carboxymethylcellulose sodium (CMC-Na) to a final DMSO concentration of ≤5% [1] - Sample collection & detection: Glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed at the end of treatment. Mice were euthanized, and liver, white adipose tissue, and skeletal muscle were collected for Western blot (pAMPKα) and lipid quantification; serum was collected for biochemical analysis (glucose, insulin, lipids) [1] |
| ADME/Pharmacokinetics |
Oral bioavailability: 42% (mice, 10 mg/kg orally) [1] - Half-life (t₁/₂): 3.8 hours (mice, intravenous); 5.2 hours (mice, orally) [1] - Volume of distribution (Vd): 2.1 L/kg (mice, intravenous) [1] - Metabolism: Primarily metabolized in the liver via cytochrome P450 2C9 and 3A4; no major active metabolites [1] - Excretion: 58% excreted in feces, 32% in urine (mice, 24 hours after administration) [1]
|
| Toxicity/Toxicokinetics |
In vitro toxicity: In 3T3-L1, HepG2 and normal human hepatocytes, CC₅₀ > 30 μM [1]
- Acute in vivo toxicity: No death or obvious toxic symptoms (drowsiness, diarrhea) were observed in mice when BC1618 was administered orally at doses up to 200 mg/kg [1] - Subchronic toxicity (4 weeks, mice): BC1618 (20 mg/kg, once daily, orally) did not cause significant changes in hematological parameters (white blood cells, red blood cells, platelets) or liver and kidney function indicators (ALT, AST, creatinine, urea nitrogen) [1] - Plasma protein binding: 93% (human plasma, ultrafiltration) [1] |
| References | |
| Additional Infomation |
BC1618 is a synthetic small molecule Fbxo48 inhibitor, which is a component of the SCF (Skp1-Cullin-F-box) E3 ubiquitin ligase complex [1]. Its mechanism of action is to bind to the substrate recognition domain of Fbxo48, blocking its interaction with pAMPKα, thereby inhibiting the ubiquitination and degradation of pAMPKα and activating the AMPK signaling pathway to improve insulin sensitivity and lipid metabolism [1]. Fbxo48 overexpression is associated with insulin resistance in obese humans and mice; BC1618 targets this pathway to improve metabolic disorders [1]. This compound has potential application value in the treatment of metabolic diseases such as type 2 diabetes, obesity, and non-alcoholic fatty liver disease (NAFLD) [1].
|
| Molecular Formula |
C24H24F3NO2
|
|---|---|
| Molecular Weight |
415.4481
|
| Exact Mass |
415.18
|
| Elemental Analysis |
C, 69.38; H, 5.82; F, 13.72; N, 3.37; O, 7.70
|
| CAS # |
2222094-18-8
|
| PubChem CID |
134417552
|
| Appearance |
White to off-white solid powder
|
| LogP |
5.2
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
9
|
| Heavy Atom Count |
30
|
| Complexity |
448
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
LGTYABNNHILKHF-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C24H24F3NO2/c25-24(26,27)21-11-13-23(14-12-21)30-18-22(29)17-28(15-19-7-3-1-4-8-19)16-20-9-5-2-6-10-20/h1-14,22,29H,15-18H2
|
| Chemical Name |
2-Propanol, 1-[bis(phenylmethyl)amino]-3-[4-(trifluoromethyl)phenoxy]-
|
| Synonyms |
BC1618BC 1618BC-1618
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~240.70 mM)
H2O : < 0.1 mg/mL |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (6.02 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.02 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. View More
Solubility in Formulation 3: 5 mg/mL (12.04 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4070 mL | 12.0351 mL | 24.0703 mL | |
| 5 mM | 0.4814 mL | 2.4070 mL | 4.8141 mL | |
| 10 mM | 0.2407 mL | 1.2035 mL | 2.4070 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
