CM002
CM002 is a circadian clock activator. CM002 inhibits the lineage commitment and terminal differentiation of preadipocytes by activating the circadian clock, thereby blocking the adipogenesis process driven by Wnt signaling-mediated transcriptional induction. CM002 attenuates lipid storage in a clock-dependent manner via inhibition of the lipogenic program in mature adipocytes. CM002 enhances circadian clock output across various adipose depots in both lean and obese mice through BMAL1/CLOCK-dependent metabolic reprogramming, inhibits adipocyte development and hypertrophy, and improves insulin sensitivity. CM002 can be used in research on obesity and type 2 diabetes.
For research use only. We do not sell to patients.
- Formula: C15H24Cl3N5
- Molecular Weight:380.74
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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All Nuclear Hormone Receptor 4A/NR4A Isoforms
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Biological Activity
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PARP-1 |
RORα |
GLUT4 |
REV-ERBα |
Wnt1 |
CM002 is used in U2OS reporter cells to screen for compounds with circadian clock-activating activity[1].
CM002 (0.5-1 µM; 5 days) exhibits a dose-dependent shortening of the circadian period with a circadian clock-activating effect, without significantly affecting amplitude in U2OS reporter gene cells[1].
CM002 (0.5-1 µM; 6 h) induces the mRNA expression of core clock genes (CLOCK, Bmal1, Nr1d1) in C3H10T1/2 cells[1].
CM002 (0.5-1 µM; 8 days of induced differentiation) potently inhibits adipogenesis in C3H10T1/2 cells, suppressing approximately 50% of lipid accumulation at a concentration of 1 µM[1].
CM002 (1 µM; 8 days of induced differentiation) almost completely eliminates the key adipogenic factors C/EBPα and PPARγ and substantially downregulates FABP4 and FASN protein expression in C3H10T1/2 cells[1].
CM002 (0.5-1 µM; 6 days of induced differentiation) dose-dependently inhibits cell maturation in primary preadipocytes from normal mice (FloxCtr). The inhibitory effect of CM002 is markedly attenuated in Bmal1-deficient cells[1].
CM002 (0.5-1 µM; 6 h) upregulates the mRNA expression of Wnt ligands (Wnt1, Wnt10a) in 3T3-L1 preadipocytes[1].
CM002 (1 µM; 8 days of induced differentiation) reactivates/maintains β-catenin protein levels in C3H10T1/2 cells[1].
CM002 (0.1-0.5 µM) activates Wnt activity under basal conditions in cells transfected with the TOPFlash reporter; under Wnt3a stimulation, it exhibits greater activation potency to Wnt than chlorhexidine (HY-B1248)[1].
CM002 (1 µM; treatment for 48 h post-differentiation) significantly reduces lipid content in primary mature adipocytes from mice (drug administration on day 4 of differentiation). CM002 reduces FASN and FABP4 protein expression in mouse primary mature adipocytes. CM002 induces the mRNA expression of clock genes (CLOCK, Dbp, Nr1d2) thermogenic and lipolytic genes (Ucp1, Hsl), and a marker of mitochondrial biogenesis (Pgc-1α) in mouse primary mature adipocytes. CM002 significantly reduces lipid accumulation in primary mature adipocytes from control mice (FloxCtr), whereas its lipid storage-suppressive effect is completely lost in Bmal1-deficient mature adipocytes [1].
CM002 (1 µM; 10-12 days of induced differentiation) strongly inhibits adipogenic maturation in human primary preadipocytes [1].
CM002 (1-2 µM; treatment for 6 days post-differentiation) significantly suppresses lipid deposition in human late-stage differentiated adipocytes. CM002 strongly induces the expression of clock proteins (BMAL1, RORα) as well as lipid synthesis and transport-related proteins (FASN, FABP4) in human adipocytes[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:C3H10T1/2 mesenchymal precursor cells, 3T3-L1 preadipocytes
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Concentration:0.5 µM, 1 µM
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Incubation Time:6 h
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Result:Induced the upregulation of core clock genes CLOCK and Bmal1, as well as their direct target gene Nr1d1.
Induced the upregulation of upstream Wnt ligands Wnt1 and Wnt10a.
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Cell Line:Mature adipocytes differentiated from mouse primary preadipocytes (control FloxCtr and Bmal1-knockout BMKO)
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Concentration:1 μM
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Incubation Time:48 h after 4 days of initial induced differentiation
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Result:Significantly reduced the amount of lipid storage in mature adipocytes and decreased the levels of FASN and FABP4 proteins.
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Cell Line:Mature adipocytes differentiated from mouse primary preadipocytes (control FloxCtr and Bmal1-knockout BMKO)
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Concentration:1 μM
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Incubation Time:48 h after 4 days of initial induced differentiation.
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Result:Induced the upregulation of circadian clock genes (CLOCK, Dbp, Nr1d2), a thermogenic regulator (Ucp1), a lipolytic enzyme (Hsl), and a mitochondrial marker (Pgc-1α).
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Cell Line:C3H10T1/2 cells, human primary preadipocytes
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Concentration:1 µM, 2 µM
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Incubation Time:8 days (mouse cells) or 12 days (human cells) of induced differentiation
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Result:Nearly abolished the expression of key adipogenic factors CEBP/α and PPARγ and markedly downregulated the levels of FABP4 and FASN in mouse cell lines.
Reactivated (upregulated) the expression of β-catenin protein in C3H10T1/2 cells differentiated for 6 to 8 days.
Induced the expression of clock proteins BMAL1 and RORα in human adipocytes.
Concurrently inhibited proteins involved in lipid synthesis and transport (FASN, FABP4) in human adipocytes.
CM002 (5 mg/kg or 15 mg/kg; intraperitoneal injection; 3 times weekly for 18 days) exerts metabolic-regulating and anti-obesity effects in 20–24-week-old C57BL/6J mice fed a normal diet. CM002 induces and enhances the expression of circadian clock proteins in adipose tissue and skeletal muscle. CM002 causes a significant reduction in body weight (a decrease of approximately 15%) in the mice. CM002 significantly inhibits adipocyte hypertrophy in epididymal white adipose tissue (eWAT) and inguinal white adipose tissue (iWAT), and reduces lipid storage in interscapular brown adipose tissue (BAT). CM002 significantly downregulates the protein expression of adipogenic factors and key regulators/enzymes of adipogenesis in eWAT. CM002 lowers fasting plasma free fatty acid (FFA) and fasting blood glucose levels, while enhancing glucose clearance and insulin sensitivity. CM002 increases the expression of insulin-responsive glucose transporters and markers of mitochondrial abundance/activity in skeletal muscle[1]. CM002 (5 mg/kg; i.p.; once daily; recorded for 4 consecutive days) regulates overall energy homeostasis in normal-diet-fed C57BL/6J mice monitored in metabolic cages. CM002 induces the mice to preferentially utilize fat oxidation over carbohydrates as an energy source[1].
CM002 (5 mg/kg; intraperitoneal injection; once daily for 7 consecutive days) induced a weight loss of up to 8 g within one week in a high-fat diet-induced obesity mouse model (C57BL/6J mice aged 14–20 weeks fed a 45% high-fat diet for 8 weeks). CM002 significantly reduced the wet tissue weight of brown adipose tissue (BAT) and decreased lipid accumulation. CM002 downregulated the protein expression of adipogenic factors and lipogenic enzymes in inguinal white adipose tissue and brown adipose tissue. CM002 significantly reduced circulating plasma free fatty acid levels[1]. CM002 (7 mg/kg; i.p.; 3 times a week; for 16 consecutive days) in a high-fat diet-induced obese C57BL/6J mouse model (initiated in 14-20-week-old mice fed a 45% high-fat diet for 8 weeks) reproduces the weight-loss effect (approximately 8 g of weight loss within 16 days) through this low-frequency dosing regimen, and this body weight reduction is entirely driven by the loss of fat mass, with no significant changes in total lean mass. CM002 significantly reduces the wet weights of various fat depots, including eWAT, iWAT, and BAT. CM002 fully preserves skeletal muscle mass[1]
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Wild-type C57BL/6J mice fed either a normal diet or a high-fat diet[1]
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Dosage:5 mg/kg
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Administration:i.p.; once daily; for 15 consecutive days (normal diet) or 7 days (high-fat diet)
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Result:Showed no obvious hepatotoxicity.
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Animal Model:20-24-week-old C57BL/6J mice fed a normal diet[1]
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Dosage:5 mg/kg, 15 mg/kg
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Administration:i.p.; 3 times a week; for 18 days
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Result:Induced and enhanced the expression of circadian clock proteins (BMAL1, RORα, and DBP) in adipose tissue and skeletal muscle.
Led to a significant decrease in body weight (a reduction of approximately 15%), which was primarily attributed to the loss of fat mass, alongside an increase in the relative percentage of total lean mass.
Significantly inhibited adipocyte hypertrophy in epididymal white adipose tissue (eWAT) and inguinal white adipose tissue (iWAT), and reduced lipid storage in interscapular brown adipose tissue (BAT).
Significantly downregulated the protein expression of adipogenic factors (C/EBPα and PPAR γ) and master regulators/enzymes of lipogenesis (SREBP-1c and FASN) in eWAT.
Lowered fasting plasma free fatty acid (FFA) and fasting blood glucose levels, and demonstrated enhanced glucose clearance and insulin sensitivity in the glucose tolerance test (GTT) and insulin tolerance test (ITT).
Increased the expression of the insulin-responsive glucose transporter (GLUT4) and markers of mitochondrial abundance/activity (PGC-1α, SDHB, and TOM20) in skeletal muscle.
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Animal Model:Normal-diet-fed C57BL/6J mice monitored in metabolic cages[1]
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Dosage:5 mg/kg
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Administration:i.p.; once daily; recorded for 4 consecutive days
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Result:Regulated overall energy homeostasis. It induced the mice to preferentially utilize fat oxidation over carbohydrates as an energy source.
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Animal Model:High-fat diet-induced obese (DIO) C57BL/6J mouse model (initiated in 14-20-week-old mice fed a 45% high-fat diet for 8 weeks)[1]
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Dosage:5 mg/kg
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Administration:i.p.; once daily; for 7 consecutive days
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Result:Led to a significant and rapid weight loss (up to 8 g of weight reduction) within a week.
Significantly decreased the tissue wet weight of brown adipose tissue (BAT) and histologically exhibited a marked reduction in lipid accumulation across all examined fat depots.
Decreased the protein expression of adipogenic factors and lipogenic enzymes in inguinal white and brown adipose tissues.
Significantly reduced circulating plasma free fatty acid levels (fasting blood glucose showed a downward trend, but serum triglyceride levels remained unchanged).
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Animal Model:High-fat diet-induced obese (DIO) C57BL/6J mouse model (initiated in 14-20-week-old mice fed a 45% high-fat diet for 8 weeks) [1]
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Dosage:7 mg/kg
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Administration:i.p.; 3 times a week; for 16 consecutive days
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Result:Reproduced the weight-loss effect (approximately 8 g of weight loss within 16 days) in this low-frequency dosing regimen.
Significantly reduced the wet weights of various fat depots, including eWAT, iWAT, and BAT.
Fully preserved skeletal muscle mass.
Chemical Information
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Molecular Weight 380.74
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Formula C15H24Cl3N5
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SMILES
ClC1=CC=C(NC(NC(NC/C=C/CCCC)=N)=N)C=C1.Cl.Cl
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
CM002 Related Classifications
HY-184895 Related Classifications
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- CM002
- CM 002
- CM-002
- Cryptochrome
- REV-ERB
- Nuclear Hormone Receptor 4A/NR4A
- FABP
- PARP
- Fatty Acid Synthase (FASN)
- Wnt
- β-catenin
- Hormone-Sensitive Lipase (HSL)
- PGC-1α
- ROR
- GLUT
- Circadian clock
- Wnt signaling
- Adipogenesis process
- Lipid storage
- Lipogenic pathways
- Adipocyte hypertrophy
- Insulin sensitivity
- Obesity
- Type 2 diabetes
- Inhibitor
- inhibitor
- inhibit