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Rotundic acid is an orally effective triterpenoid with a Kd value of 51.3 µM for PTP1B. Rotundic acid downregulates the AKT/mTOR pro-survival pathway and modulates the MAPK pathway. Rotundic acid induces cell cycle S-phase arrest, DNA damage and apoptosis; it inhibits migration, invasion, angiogenesis and proliferation of cancer cells. Rotundic acid improves leptin sensitivity, regulates gut microbiota and reduces cellular senescence. Rotundic acid can be used in research related to hepatocellular carcinoma, obesity, aging, acute lung injury and type 2 diabetes.
For research use only. We do not sell to patients.
Rotundic acid is an orally effective triterpenoid with a Kd value of 51.3 µM for PTP1B. Rotundic acid downregulates the AKT/mTOR pro-survival pathway and modulates the MAPK pathway. Rotundic acid induces cell cycle S-phase arrest, DNA damage and apoptosis; it inhibits migration, invasion, angiogenesis and proliferation of cancer cells. Rotundic acid improves leptin sensitivity, regulates gut microbiota and reduces cellular senescence. Rotundic acid can be used in research related to hepatocellular carcinoma, obesity, aging, acute lung injury and type 2 diabetes[1][2][3][4].
IC50 & Target
mTOR
p38 MAPK
Cellular Effect
Cell Line
Type
Value
Description
References
A-375
IC50
16.58 μM
Compound: 1, RA, Rotundic acid
Cytotoxicity against human A375 cells after 24 hrs by MTT assay
Cytotoxicity against human A375 cells after 24 hrs by MTT assay
Rotundic acid (10-30 μM) dose-dependently inhibits the migration of HUVEC cells[1]. Rotundic acid (0-1000 μM) is a non-competitive inhibitor of human PTP1B, whose optimal inhibitory effect depends on the C-terminus of this protein. The IC50 values against PTP1B1-298, PTP1B1-321 and PTP1B1-393 are 2 mM, 481.8 μM and 443.7 μM, respectively[2]. Rotundic acid (3.125-100 μM; 48 h) significantly extends the replicative lifespan of BY4741 yeast cells, with a maximum extension of up to 135% at the concentration of 12.5 μM[2]. Rotundic acid (5-20 μM; 24 h) reduces cellular senescence levels in senescent WI-38 human embryonic lung fibroblasts, as evidenced by a decrease in SA-β-gal-positive cells; it also promotes cell proliferation at a concentration of 12.5 μM[2]. Rotundic acid (15-60 μM; 24 h) shows no cytotoxicity against RAW264.7 mouse macrophages, and its concentration can reach up to 60 μM after 24 h of incubation[3]. Rotundic acid (15-60 μM; 1 h pretreatment) dose-dependently reduces nitrite production in LPS (HY-D1056)-stimulated RAW264.7 murine macrophages[3]. Rotundic acid (15-60 μM; 1 h pretreatment) inhibits LPS-induced release of TNF-α and IL-6 in RAW264.7 mouse macrophages[3]. Rotundic acid (15-60 μM; 1 h pretreatment) regulates multiple inflammatory signaling pathways in LPS-stimulated RAW264.7 murine macrophages, including inhibiting the activation of NF-κB, MAPK and PI3K/Akt/mTOR, upregulating the Keap-1/Nrf2/HO-1 signaling pathway and reducing the expression of TLR4[3]. Rotundic acid (15-60 μM; 1 h pretreatment) reduces LPS-induced NO release, ROS production and intracellular Ca2+ levels in RAW264.7 murine macrophages[3]. Rotundic acid exhibits significant cytotoxic activity against Daoy, Hep-2 and MCF-7 human tumor cell lines[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Showed no cytotoxic effect on RAW264.7 macrophages at all tested concentrations, with cell viability remaining above 80% relative to the control group.
1 h pretreatment, followed by 18 h LPS stimulation
Result:
Significantly decreased the release of TNF-α and IL-6 at all tested concentrations, with consistent, significant inhibition across doses. Increased TNF-α and IL-6 release strongly when LPS was applied alone.
In Vivo
Rotundic acid (50 mg/kg; i.p.; once every 2 days; for 60 consecutive days) achieves a 75.6% tumor growth inhibition rate in a Balb/c nude mouse model with human hepatocellular carcinoma HepG2 cell xenografts. It also reduces tumor weight, inhibits proliferation and angiogenesis, induces cell apoptosis, and causes no significant body weight loss[1]. Rotundic acid (40 mg/kg; i.p.; 1 week per month for 6 consecutive months) extends the average lifespan of naturally aged male C57BL/6J mice by 16.2% and improves their aging-related functional indicators[2]. Rotundic acid (40 mg/kg; i.p.; once daily; for 14 consecutive days) reduces the body weight of high-fat diet-induced obese mice by up to 26.3% and decreases their food intake in a dose-dependent manner[2]. Rotundic acid (i.p.; 40 mg/kg; once daily for 14 consecutive days) reduces body weight by 25.1% in high-fat diet-induced obese mice with an average body weight of approximately 58 g, while also decreasing their food intake, reducing adipose tissue weight, and downregulating plasma leptin levels[2]. Rotundic acid (40 mg/kg; i.p.; once daily for 14 consecutive days) exerts no effect on body weight, food intake, or adipose tissue mass in normal lean male C57BL/6N mice[2]. Rotundic acid (40 mg/kg; i.p.; once daily for 14 consecutive days) improves glucose homeostasis and insulin sensitivity in high-fat diet-induced obese mice[2]. Rotundic acid (20-40 mg/kg; i.p.) reduces xylene-induced ear swelling in mice by more than 80% and ameliorates associated pathological tissue damage[3]. Rotundic acid (20-40 mg/kg; i.p.) increases the 144-hour survival rate of LPS-induced endotoxic shock mice to 30%[3]. Rotundic acid (10-40 mg/kg; i.p.) reduces LPS-induced levels of inflammatory markers, ameliorates pulmonary function impairment, and alleviates lung pathological damage in a mouse model of acute lung injury[3]. Rotundic acid (40 mg/kg; oral gavage; daily; 8 weeks) improves glucose and lipid metabolism, reduces blood pressure, protects against cardiovascular, hepatic and renal damage, alleviates oxidative stress and inflammatory responses, and restores gut microbiota dysbiosis induced by a high-fat diet combined with low-dose streptozotocin in type 2 diabetic rats[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Reduced mean tumor volume to 78.95 mm3 (vs. 323.64 mm3 in controls), achieving 75.6% tumor growth inhibition. Reduced tumor weights significantly compared to controls. Showed no significant body weight loss. Reduced expression of proliferation marker Ki-67, angiogenesis marker CD-31, phosphorylated AKT, and phosphorylated mTOR in tumor tissue. Increased expression of phosphorylated p38 MAPK in tumor tissue. Induced apoptosis via increased cleaved PARP and cleaved caspase-3 in tumor tissue.
Reduced body weight in a dose-dependent manner, with the 40 mg/kg dose causing a 26.3% decrease. Reduced daily food intake by 62.3% in the first week of 40 mg/kg treatment.
i.p.; two doses: 2 hours before LPS, 4 hours after LPS
Result:
Decreased LPS-induced increases in blood lymphocytes, neutrophils, and white blood cells. Reduced levels of TNF-α, IL-6, and IL-1β in serum, bronchoalveolar lavage fluid, and lung tissue homogenate. Reduced myeloperoxidase activity in lung tissue. Significantly recovered mouse lung function including peak expiratory flow, dynamic lung compliance, inspiratory resistance, expiratory resistance, and minute ventilation volume. Ameliorated LPS-induced alveolar interstitial exudation, alveolar structural destruction, and inflammatory cell infiltration observed via H&E staining.
Animal Model:
Sprague-Dawley (5-week-old male, weight 180-220 g, type 2 diabetes induced by high-fat diet + low-dose streptozotocin)[4]
Dosage:
40 mg/kg
Administration:
i.g.; daily; 8 weeks
Result:
Increased body weight compared to T2D model rats. Decreased water intake and increased food intake compared to T2D model rats. Reduced fasting glucose, glycated hemoglobin A1c (HbA1c), and insulin levels compared to T2D model rats. Reduced glucose area under the curve (AUC) for OGTT and ITT, and reduced HOMA-IR index compared to T2D model rats. Significantly reduced serum total glyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and free fatty acid (FFA) levels, and increased high-density lipoprotein cholesterol (HDL-C) levels compared to T2D model rats. Reduced systolic blood pressure (SYS), diastolic blood pressure (DIA), mean arterial pressure (MAP), and serum angiotensin-2 (ANG-2) levels compared to T2D model rats. Significantly reduced serum myocardial enzymes (α-HBDH: 151.9 U/L, CK: 0.418 U/L, CK-MB: 191.7 U/L, LDH: 1854.0 U/L), C-reactive protein (CRP: 422.7 pg/mL), endothelin-1 (ET-1: 48.9 pg/mL), alanine aminotransferase (ALT: 44.6 IU/L), aspartate aminotransferase (AST: 99.32 IU/L), alkaline phosphatase (ALP: 15.1 KU/100 mL), uric acid (UA: 131.0 μmol/L), and urea nitrogen (BUN: 5.3 mmol/L) compared to T2D model rats. Increased serum superoxide dismutase (SOD: 246.7 U/L) and interleukin-4 (IL-4: 55.2 pg/mL) levels compared to T2D model rats. Decreased serum malondialdehyde (MDA: 4.73 nmol/mL), tumor necrosis factor-α (TNF-α: 259.1 pg/mL), interferon-γ (INF-γ: 16.6 pg/mL), interleukin-1β (IL-1β: 11.0 pg/mL), and interleukin-6 (IL-6: 8.7 pg/mL) levels compared to T2D model rats. Increased Chao1 and Shannon α-diversity indices compared to T2D model rats. Reversed the elevated Firmicutes-to-Bacteroidetes ratio seen in T2D model rats. Increased relative abundances of beneficial/commensal genera Prevotella, Ruminococcus, Leuconostoc, and Streptococcus compared to T2D model rats. Decreased relative abundances of opportunistic pathogen genera Klebsiella and Proteus compared to T2D model rats.
DMSO : 100 mg/mL (204.62 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Preparing Stock Solutions
ConcentrationSolventMass
1 mg
5 mg
10 mg
1 mM
2.0462 mL
10.2312 mL
20.4625 mL
5 mM
0.4092 mL
2.0462 mL
4.0925 mL
10 mM
0.2046 mL
1.0231 mL
2.0462 mL
View the Complete Stock Solution Preparation Table
*Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles. Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day. The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Solubility: 2.5 mg/mL (5.12 mM); Suspended solution; Need ultrasonic
This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 2
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: 2.5 mg/mL (5.12 mM); Suspended solution; Need ultrasonic
This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Protocol 3
Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.5 mg/mL (5.12 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (25.0 mg/mL) to 900 μLCorn oil, and mix evenly.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
Dosage
mg/kg
Animal weight (per animal)
g
Dosing volume (per animal)
μL
Number of animals
Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO+
%
+
%
Tween-80
+
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO,
. All of co-solvents are available by MedChemExpress (MCE).
, Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration:
mg/mL
Method for preparing stock solution:
mg
drug dissolved in
μL
DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take
μL DMSO stock solution, add
μL .
μL , mix evenly, next add
μL Tween 80, mix evenly, then add
μL Saline.
Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution
If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
*Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles. Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.
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