| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
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| ln Vitro |
For 11β-HSD2, mineralocorticoid receptor (MR), and glucocorticoid receptor (GR), INCB13739 exhibits >1000-fold selectivity [1].
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|---|---|
| ln Vivo |
INCB13739 (oral) is efficiently distributed in adipose tissue and inhibits 11β-HSD1 activity by >90% for at least 24 hours after administration [1]. INCB13739 (3 mg/kg IV; 10 mg/kg PO; once) demonstrated good oral bioavailability in both rats and cynomolgus monkeys [1]. Pharmacokinetic parameters of INCB13739 in rats [1]. IV (3 mg/kg) PO (10 mg/kg) Cmax (μM) 6.46 ± 2.41 AUC0-24 (ng/mL*h) 11.2 ± 3.27 t1/2 (h) 1.4 ± 0.2 1.2 ± 0.3 CL ((L /h)/kg) 1.0 ± 0.2 Vdss (L/kg) 1.6 ± 0.5 F (%) 51 ± 15
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| Animal Protocol |
Animal/Disease Models: Rat, cynomolgus monkey[1]
Doses: 3 mg/kg (IV), 10 mg/ kg (PO) Route of Administration: IV and PO, once (pharmacokinetic/PK/PK analysis) Experimental Results: Demonstrated good oral administration in both rats (F%=51 ± 15%) and cynomolgus monkeys (F%=43%) bioavailability. |
| References | |
| Additional Infomation |
INCB13739 is developed as a new treatment for type 2 diabetes. It is an orally available small molecule inhibitor of 11beta-HSD1 (11-beta hydroxysteroid dehydrogenase type 1). 11beta-HSD1 is an enzyme that appears to be critical to the development of type 2 diabetes.
Drug Indication Investigated for use/treatment in diabetes mellitus type 2 and diabetes prevention. Mechanism of Action INCB13739 is an inhibitor of 11beta-HSD1 (11-beta hydroxysteroid dehydrogenase type 1). 11beta-HSD1 is an enzyme that appears to be critical to the development of type 2 diabetes. INCB13739 completely inhibits the production of intra-adipose and intra-hepatic cortisol by 11beta-HSD1, while maintaining normal systemic cortisol levels, which are essential for immune function and response to stress. Pharmacodynamics 11beta-HSD1 is an enzyme that converts cortisone into the potent biologically active hormone cortisol. This conversion occurs intra-cellularly within several key metabolic tissues including the liver, adipose, muscle and pancreas. Cortisol acts as an antagonist of insulin action, and 11beta-HSD1 mediated production of cortisol has been hypothesized to contribute to human insulin resistance and type 2 diabetes. INCB13739 inhibits 11beta-HSD1 and has the potential to provide a broad spectrum impact on the multiple components seen in patients with type 2 diabetes. |
| Molecular Formula |
C28H25N3O4
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|---|---|
| Molecular Weight |
467.52
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| Exact Mass |
467.184
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| CAS # |
869974-19-6
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| PubChem CID |
66662059
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
2.9
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
35
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| Complexity |
864
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C1C=CC=C2C=1C(=O)O[C@@]12CCN(C1)C(=O)C1(CC1)C1C=CC(C2=CN=C(C(NC)=O)C=C2)=CC=1
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| InChi Key |
BDQCDIWFPIDPQU-NDEPHWFRSA-N
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| InChi Code |
InChI=1S/C28H25N3O4/c1-29-24(32)23-11-8-19(16-30-23)18-6-9-20(10-7-18)27(12-13-27)26(34)31-15-14-28(17-31)22-5-3-2-4-21(22)25(33)35-28/h2-11,16H,12-15,17H2,1H3,(H,29,32)/t28-/m0/s1
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| Chemical Name |
N-methyl-5-[4-[1-[(1R)-3-oxospiro[2-benzofuran-1,3'-pyrrolidine]-1'-carbonyl]cyclopropyl]phenyl]pyridine-2-carboxamide
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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) |
DMSO : ~125 mg/mL (~267.37 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.45 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.45 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.45 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1389 mL | 10.6947 mL | 21.3895 mL | |
| 5 mM | 0.4278 mL | 2.1389 mL | 4.2779 mL | |
| 10 mM | 0.2139 mL | 1.0695 mL | 2.1389 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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