| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg | |||
| 250mg | |||
| Other Sizes |
| Targets |
Implitapide targets the microsomal triglyceride transfer protein (MTP), a key enzyme involved in the assembly and secretion of apolipoprotein B-containing lipoproteins (VLDL and chylomicrons) in the liver and intestine. MTP mediates triglyceride absorption and chylomicron secretion from the intestine and VLDL secretion from the liver by linking lipid molecules with apolipoprotein B (apoB). Inhibition of MTP reduces the level of all apoB-containing lipoproteins, including LDL.
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|---|---|
| ln Vitro |
Using a recombinant human form complexed with protein disulfide isomerase, implitapide reduces MTP activity (IC50=10 nM) and inhibits the production of apoB-containing very low-density lipoprotein (VLDL)-like lipids by human hepatoma cells (HepG2) with an IC50 value. Protein at 1.1 nM [1].
In vitro, Implitapide potently inhibits MTP activity. Using a recombinant human form of MTP complexed with protein disulphide isomerase, it shows an IC50 of 10 nM. Furthermore, Implitapide inhibits the secretion of apoB-containing very low-density lipoprotein (VLDL)-like lipoproteins from human hepatoma cells (HepG2) with an even greater potency (IC50: 1.1 nM). |
| ln Vivo |
Implitapide (3.2 mg/kg/d) significantly lowered plasma lipid levels to levels near to or below dietary (CD) levels after 4 and 8 weeks of therapy (p<0.01). Implitapide (3.2 mg/kg/d) effectively reduces lipid-stained lesions in Western diet (WD)-fed mice. Compared with the WD group, Inprotapid (3.2 mg/kg/d) significantly reduced the lesion area by 83% (p<0.01). Feeding WD ApoE KO mice for 14 weeks containing imprecitap (1, 5, and 15 mg/kg/d) has been demonstrated to dramatically reduce plaque area (66%, 78%, and 93%, respectively). and lipid percentage within the plaque (4.3, 2.6, and 0%, respectively, compared with 9.5% in the control group). In apoE KO mice, Implitapide at a dose of roughly 3.2 mg/kg/d dramatically decreased lipid-stained aortic lesions by 83% [1].
In vivo, Implitapide demonstrates significant efficacy in reducing atherosclerotic lesions and plasma lipids. In apolipoprotein E knockout (KO) mice fed a Western-type diet, administering Implitapide (3.2 mg/kg/d) reduced lipid-stained aortic lesions by 83%. In a 14-week study with varying doses (1, 5, and 15 mg/kg/d), plaque area was reduced by 66%, 78%, and 93%, respectively, with lipid content within plaques decreasing to near-zero levels at the highest dose. |
| Enzyme Assay |
MTP inhibition is assessed using an in vitro assay with a recombinant human MTP complex. The assay measures the transfer of radiolabeled lipids from donor to acceptor vesicles. Implitapide is incubated with the MTP complex, and the residual transfer activity is measured to calculate the IC50, which is reported at 10 nM.
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| Cell Assay |
The functional consequences of MTP inhibition are evaluated in cultured hepatocytes (e.g., HepG2 cells). Cells are treated with Implitapide, and the secretion of apolipoprotein B-containing lipoproteins into the culture medium is quantified. The IC50 for inhibiting apoB secretion from HepG2 cells is 1.1 nM, demonstrating its potent cellular activity.
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| Animal Protocol |
In vivo efficacy is evaluated in atherosclerosis-prone animal models such as apolipoprotein E-deficient (ApoE-/-) mice. Implitapide is administered orally, and plasma lipid profiles are measured. Atherosclerotic lesion area is quantified in the aortic root after the treatment period. Significant reductions in lesion area and lipid content have been observed at doses as low as 1 mg/kg/d.
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| ADME/Pharmacokinetics |
As a lipophilic small molecule, Implitapide is expected to be well absorbed after oral administration and to distribute to the liver and intestine, its primary sites of action. Its pharmacokinetic profile is characterized by a long half-life suitable for once-daily dosing. Its molecular weight of 531.69 g/mol is consistent with other small molecule inhibitors designed for oral bioavailability.
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| Toxicity/Toxicokinetics |
Given its mechanism of reducing lipid absorption and synthesis, Implitapide may cause gastrointestinal side effects, including steatorrhea and diarrhea, due to fat malabsorption. Hepatic fat accumulation (hepatic steatosis) is a potential class effect of MTP inhibitors, which has been a significant concern in its clinical development.
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| References | |
| Additional Infomation |
Implitapide is a microsomal triglyceride transfer protein (MTP) inhibitor. Implitapide is a microsomal triglyceride transfer protein (MTP) inhibitor with lipid-lowering activity. In animal models, ippulitapais reduces total cholesterol and triglyceride levels and inhibits the progression of atherosclerotic lesions by inhibiting MTP. Indications: For the treatment of atherosclerosis. Mechanism of Action: MTP mediates the absorption of triglycerides and the secretion of chylomicrons from the intestine and very low-density lipoprotein (VLDL) from the liver by linking lipid molecules to apolipoprotein B (apoB). Inhibition of MTP reduces the levels of all apoB-containing lipoproteins, including LDL.
Implitapide was investigated as a potential therapeutic for dyslipidemia and atherosclerosis but did not advance to market, likely due to safety concerns, particularly hepatic steatosis and gastrointestinal intolerance. It remains a valuable tool for studying lipoprotein metabolism and the effects of MTP inhibition. Its DrugBank ID is DB04852. |
| Molecular Formula |
C35H37N3O2
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|---|---|
| Molecular Weight |
531.7
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| Exact Mass |
531.288
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| Elemental Analysis |
C, 79.06; H, 7.01; N, 7.90; O, 6.02
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| CAS # |
177469-96-4
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| Related CAS # |
Implitapide Racemate;177277-99-5
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| PubChem CID |
5745206
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| Appearance |
White to off-white solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
739.3±60.0 °C at 760 mmHg
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| Flash Point |
400.9±32.9 °C
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| Vapour Pressure |
0.0±2.6 mmHg at 25°C
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| Index of Refraction |
1.653
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| LogP |
6.7
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
40
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| Complexity |
824
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CC1=CC(=NC2=C1C3=CC=CC=C3N2CC4=CC(=CC=C4)[C@H](C5CCCC5)C(=O)N[C@@H](CO)C6=CC=CC=C6)C
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| InChi Key |
AMNXBQPRODZJQR-DITALETJSA-N
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| InChi Code |
InChI=1S/C35H37N3O2/c1-23-19-24(2)36-34-32(23)29-17-8-9-18-31(29)38(34)21-25-11-10-16-28(20-25)33(27-14-6-7-15-27)35(40)37-30(22-39)26-12-4-3-5-13-26/h3-5,8-13,16-20,27,30,33,39H,6-7,14-15,21-22H2,1-2H3,(H,37,40)/t30-,33-/m0/s1
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| Chemical Name |
(2S)-2-cyclopentyl-2-[3-[(2,4-dimethylpyrido[2,3-b]indol-9-yl)methyl]phenyl]-N-[(1R)-2-hydroxy-1-phenylethyl]acetamide
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| Synonyms |
BAY-139952; BAY139952;
implitapida; Q70OH404HR; AEGR427; BAY-13-9952; DTXSID70870136; Implitapide; BAY-13-9952; AEGR-427
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~188.08 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.70 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8808 mL | 9.4038 mL | 18.8076 mL | |
| 5 mM | 0.3762 mL | 1.8808 mL | 3.7615 mL | |
| 10 mM | 0.1881 mL | 0.9404 mL | 1.8808 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.
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