| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Targets |
BI-187004 targets 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), an enzyme responsible for the intracellular conversion of inactive cortisone to active cortisol. 11β-HSD1 is primarily expressed in liver and adipose tissue and plays a critical role in regulating local glucocorticoid levels. By inhibiting 11β-HSD1, BI-187004 reduces cortisol production in target tissues, thereby improving insulin sensitivity and metabolic parameters.
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| ln Vitro |
In vitro, BI-187004 is a potent and selective inhibitor of 11β-HSD1 with an IC50 of 31 nM. It inhibits the enzyme's activity in converting cortisone to cortisol, thereby modulating local glucocorticoid levels. These in vitro properties make BI-187004 a valuable tool for studying 11β-HSD1 function and its role in metabolic diseases.
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| ln Vivo |
In vivo, BI-187004 was administered once daily for 14 days to eight patients with type 2 diabetes mellitus. In preclinical studies, BI-187004 had a positive impact on multiple cardiovascular and metabolic risk factors associated with metabolic syndrome, which differentiates it from other classes of type 2 diabetes drugs. It is being studied for the treatment of type 2 diabetes and metabolic syndrome.
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| Enzyme Assay |
The in vitro enzyme assay for BI-187004 involves measuring its inhibition of 11β-HSD1 enzymatic activity. Recombinant 11β-HSD1 is incubated with the compound at various concentrations in the presence of cortisone substrate and NADPH as a cofactor. Enzyme activity is measured by quantifying the conversion of cortisone to cortisol using HPLC, LC-MS/MS, or immunoassay. The IC50 for 11β-HSD1 inhibition is calculated from dose-response curves. Selectivity against 11β-HSD2 can be assessed using similar assays.
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| Cell Assay |
The in vitro cell-based assay for BI-187004 involves culturing cells that express 11β-HSD1, such as hepatocytes or adipocytes, and treating them with the compound to assess effects on cortisol production. Cells are treated with BI-187004 at various concentrations in the presence of cortisone substrate. Cortisol production is measured by ELISA or LC-MS/MS. Insulin-stimulated glucose uptake or other metabolic readouts can be assessed to evaluate functional effects of 11β-HSD1 inhibition. Cell viability is assessed using MTT or CellTiter-Glo assays.
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| Animal Protocol |
In vivo animal studies for BI-187004 have been conducted in preclinical models of metabolic syndrome and type 2 diabetes. Rodents are administered BI-187004 orally at various doses. Metabolic parameters including blood glucose, insulin sensitivity, lipid profiles, and body weight are assessed. In clinical studies, BI-187004 was administered once daily for 14 days to patients with type 2 diabetes. Standard protocols for metabolic disease models are employed.
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| ADME/Pharmacokinetics |
BI-187004 is a small molecule with favorable pharmacokinetic properties suitable for oral administration. It has a molecular weight of 342.39 and a molecular formula of C21H18N4O. The compound is a solid with ≥98% purity and is soluble in DMSO. In clinical studies, it was administered once daily for 14 days. Detailed PK parameters are available from preclinical and clinical studies.
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| Toxicity/Toxicokinetics |
The toxicity profile of BI-187004 has been evaluated in preclinical and clinical studies. As an 11β-HSD1 inhibitor, its primary safety concerns relate to effects on glucocorticoid metabolism and potential impacts on the hypothalamic-pituitary-adrenal axis. In clinical studies, the compound was well-tolerated. Standard toxicology assessments would include acute and sub-chronic toxicity studies in rodents and dogs, with endpoints including clinical signs, body weight, clinical pathology, and histopathology.
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| References | |
| Additional Infomation |
BI-187004 is a research compound and has not been approved for clinical use. It is a potent and selective inhibitor of 11β-HSD1 with an IC50 of 31 nM. BI-187004 (VTP-34072) is being studied for the treatment of type 2 diabetes and metabolic syndrome. In preclinical studies, it had a positive impact on multiple cardiovascular and metabolic risk factors associated with metabolic syndrome. The compound was administered once daily for 14 days to eight patients with type 2 diabetes mellitus.
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| Molecular Formula |
C21H18N4O
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| Molecular Weight |
342.393824100494
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| Exact Mass |
342.15
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| Elemental Analysis |
C, 73.67; H, 5.30; N, 16.36; O, 4.67
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| CAS # |
1303515-32-3
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| PubChem CID |
67223373
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| Appearance |
Solid powder
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| LogP |
3
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
26
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| Complexity |
612
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C1C[C@H]2[C@H](CC3=C2C=C(C=C3)C#N)N(C1)C(=O)C4=CC5=C(C=C4)N=CN5
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| InChi Key |
VVZNCSHIBODHMZ-UZLBHIALSA-N
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| InChi Code |
InChI=1S/C21H18N4O/c22-11-13-3-4-14-10-20-16(17(14)8-13)2-1-7-25(20)21(26)15-5-6-18-19(9-15)24-12-23-18/h3-6,8-9,12,16,20H,1-2,7,10H2,(H,23,24)/t16-,20+/m1/s1
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| Chemical Name |
(4aR,9aS)-1-(1H-Benzimidazol-6-ylcarbonyl)-2,3,4,4a,9,9a-hexahydro-1H-indeno[2,1-b]pyridine-6-carbonitrile
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| Synonyms |
BI-187004; BI 187004; BI187004; VTP-34072; VTP 34072; VTP34072;
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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 |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9206 mL | 14.6032 mL | 29.2065 mL | |
| 5 mM | 0.5841 mL | 2.9206 mL | 5.8413 mL | |
| 10 mM | 0.2921 mL | 1.4603 mL | 2.9206 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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