| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg | |||
| Other Sizes |
| Targets |
IC50: 47 nM (LTA4H)[1]
DG-051 HCl targets leukotriene A4 hydrolase (LTA4H), the enzyme that catalyzes the rate-determining step in the synthesis of the pro-inflammatory mediator LTB4. It is a potent inhibitor of LTA4H aminopeptidase activity. By inhibiting LTA4H, DG051 decreases risk of heart attack by decreasing the production of leukotriene B4 (LTB4), an end product of the leukotriene pathway and a potent promoter of inflammation. |
|---|---|
| ln Vitro |
DG051 is a strong inhibitor of LTA4H aminopeptidase activity against L-alanine p-nitroanilide (IC50 = 72 nM). DG051 inhibits human whole blood (HWB) at an IC50 of 37 nM. In the context of LTA4H inhibitor design, the chemistry team is able to design a potent DG051 (Kd=26 nM) with high aqueous solubility (>30 mg/mL) and high oral bioavailability (>80% across species) that is currently undergoing clinical evaluation for the treatment of myocardial infarction and stroke.[1] DG-051 is a first-in-class small molecule inhibitor of leukotriene A4 hydrolase (LTA4H) that is currently in Phase II clinical trials to prevent heart attacks [2].
In vitro, DG-051 HCl is a strong inhibitor of LTA4H aminopeptidase activity against L-alanine p-nitroanilide with an IC50 of 72 nM. It inhibits human whole blood (HWB) at an IC50 of 37 nM. It inhibits LTB4 biosynthesis in enzyme assays with an IC50 of 47 nM. It has a Kd of 25 nM. |
| ln Vivo |
In vivo, DG-051 HCl is an orally bioavailable LTA4H inhibitor. By inhibiting LTA4H, it reduces the production of LTB4, a potent pro-inflammatory mediator. Its activity has been studied in various preclinical models of inflammation. It is currently undergoing clinical evaluation for the treatment of myocardial infarction and stroke.
|
| Enzyme Assay |
In vitro enzyme assays for DG-051 HCl typically measure its ability to inhibit LTA4H aminopeptidase activity. The enzyme is incubated with a substrate such as L-alanine p-nitroanilide in the presence of increasing concentrations of the compound. The release of p-nitroaniline is measured spectrophotometrically. IC50 values are calculated. DG-051 has an IC50 of 47 nM in enzyme assays and 72 nM against L-alanine p-nitroanilide.
|
| Cell Assay |
Cell-based assays for DG-051 HCl involve treating human whole blood or cell cultures with the compound and measuring LTB4 production. The compound's ability to inhibit LTB4 biosynthesis is assessed by ELISA or LC-MS. DG-051 inhibits human whole blood (HWB) at an IC50 of 37 nM.
|
| Animal Protocol |
In vivo animal studies for DG-051 HCl typically involve oral administration to animal models of inflammation. LTB4 levels in plasma or tissues are measured. The compound's ability to reduce inflammation and its pharmacokinetic properties are assessed.
|
| ADME/Pharmacokinetics |
Pharmacokinetic properties of DG-051 HCl include high aqueous solubility (>30 mg/mL) and high oral bioavailability (>80% across species). The compound has a molecular weight of 426.334 and a LogP of 5.58. It is the HCl salt of the free acid DG-051.
|
| Toxicity/Toxicokinetics |
The toxicological profile of DG-051 HCl has been evaluated in preclinical studies. The compound is generally well-tolerated. Its safety profile is consistent with other LTA4H inhibitors.
|
| References |
|
| Additional Infomation |
DG051 is a novel small-molecule leukotriene A4 hydrolase (LTA4H) inhibitor. LTA4H is a protein encoded by a gene in the leukotriene pathway, which has been shown to be associated with the risk of heart attack. DG051 is designed to reduce the risk of heart attack by reducing the production of leukotriene B4 (LTB4). LTB4 is the end product of the leukotriene pathway and a potent inflammatory stimulant.
Drug Indications It is being investigated for the treatment of myocardial infarction. Mechanism of Action DG051 is a leukotriene A4 hydrolase (LTA4H) inhibitor, which has been shown to be associated with the risk of heart attack and is directly involved in the synthesis of LTB4. DG051 reduces the risk of heart attack by inhibiting LTA4H, the mechanism of which is to reduce the production of leukotriene B4 (LTB4), the end product of the leukotriene pathway and a potent inflammatory stimulant. DG-051 HCl is a potent, orally bioavailable leukotriene A4 hydrolase (LTA4H) inhibitor. It inhibits LTB4 biosynthesis by targeting the rate-determining step in its synthesis. It is a first-in-class small molecule inhibitor that is currently in Phase II clinical trials to prevent heart attacks. It is a valuable research tool for studying the role of LTB4 in inflammation and other diseases. |
| Molecular Formula |
C21H25CL2NO4
|
|---|---|
| Molecular Weight |
426.334
|
| Exact Mass |
425.116
|
| CAS # |
929915-58-2
|
| PubChem CID |
44818987
|
| Appearance |
White to light yellow solid powder
|
| LogP |
5.58
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
9
|
| Heavy Atom Count |
28
|
| Complexity |
448
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
C1C[C@H](N(C1)CCCC(=O)O)COC2=CC=C(C=C2)OC3=CC=C(C=C3)Cl.Cl
|
| InChi Key |
UCPVOTSNNAVKNE-LMOVPXPDSA-N
|
| InChi Code |
InChI=1S/C21H24ClNO4.ClH/c22-16-5-7-19(8-6-16)27-20-11-9-18(10-12-20)26-15-17-3-1-13-23(17)14-2-4-21(24)25;/h5-12,17H,1-4,13-15H2,(H,24,25);1H/t17-;/m0./s1
|
| Chemical Name |
4-[(2S)-2-[[4-(4-chlorophenoxy)phenoxy]methyl]pyrrolidin-1-yl]butanoic acid;hydrochloride
|
| Synonyms |
DG051 DG 051 DG-051 HCl
|
| HS Tariff Code |
2934.99.9001
|
| 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, 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)
|
| Solubility (In Vitro) |
DMSO : ≥ 325 mg/mL (~762.32 mM)
|
|---|---|
| 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 | 2.3456 mL | 11.7280 mL | 23.4560 mL | |
| 5 mM | 0.4691 mL | 2.3456 mL | 4.6912 mL | |
| 10 mM | 0.2346 mL | 1.1728 mL | 2.3456 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
