Clinofibrate is a new hypelipidemic agent and a competitive hydroxymethylglutaryl coenzyme A reductase with an IC50 of 0.47 mM. Clinofibrate is a derivative of clofibrate. Clinofibrate, as a antihyperlipidemic drug, activiates human liver 3alpha-hydroxysteroid dehydrogenase. The optimal pha of activation this enzyme by the compound clinofibrate was about 7.5. The concentrations giving maximum stimulation (1.8 to 2.4 fold) for clinofibrate were 50 μM. The activation by the antihyperlipidemic drug, clinofibrate, elevated both Km and Kcat (turnover number) values for the coenzyme and substrates. Clinofibrate lacks the chloro group, methyl goup on the alpha-carbon or carboxyl group. Thus, clinofibrate greatly decreased the stimulatory effects. Kinetic analysis with respect to NAPD+ exhibited that clinofibrate was nonessential activators with dissociation constants of 6 μM. These data suggest that the long-term treatment with the antihyperlipidemic drugs generates effects on the metabolism of steroid hormones and bile acids, as well as several-containing drugs mediated by the enzyme.
Cell Experiment | |
---|---|
Cell lines | |
Preparation method | |
Concentrations | |
Incubation time |
Animal Experiment | |
---|---|
Animal models | Seven-week-old Sprague-Dawley rats (SLC), six-week-old ICR-SLC mice and a one-year-old beagle dog |
Formulation | |
Dosages | 30 mg/kg |
Administration | Administered orally or intravenously |
Molecular Weight | 468.58 |
Formula | C28H36O6 |
CAS Number | 30299-08-2 |
Solubility (25°C) | DMSO 90 mg/mL |
Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
[1] Yohtaro Sato, et al. Clinofibrate improved canine lipid metabolism in some but not all breeds
Related HMG-CoA Reductase Products |
---|
Fluvastatin
Fluvastatin is the first fully synthesized, competitive HMG-CoA reductase inhibitor with an IC50 of 8 nM.Fluvastatin protects vascular smooth muscle cells from oxidative stress through an Nrf2-dependent antioxidant pathway. |
Pravastatin lactone
Pravastatin lactone is a potent HMG-CoA inhibitor. |
HMG-CoA Reductase-IN-1
HMG-CoA Reductase-IN-1 is a HMG-CoA reductase inhibitor. |
Ganomycin I
Ganomycin I is a dual inhibitor of α-Glucosidase and HMG-CoA reductase. |
Ganoderenic acid K
Ganoderenic acid K is a natural product, that can be isolated from fruiting bodies of Ganoderma lucidum. |
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2023 AbMole BioScience. All Rights Reserved.