| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| Other Sizes |
|
Razuprotafib (AKB-9778) is a novel small molecule Tie2 activator being developed in phase 2 clnical trials by Aerpio company for a number of indications including Diabetic Nephropathy, Open Angle Glaucoma and ARDS due to COVID-19. It enhances endothelial function and stabilizes blood vessels, including pulmonary and renal vasculature. Razuprotafib restores Tie2 activation to stabilize the vasculature providing breakthrough potential for reducing the severity of COVID-19 associated pulmonary and vascular pathology resulting in fewer patients requiring ventilator support, decreased time in ICU on ventilator support and more rapid and complete recovery with concomitant reduction mortality. Additionally, razuprotafib together with emerging antiviral drugs could provide the optimal combination of host and virus targeted therapy for prevention and treatment of COVID‑19 and COVID-19 related ARDS. Razuprotafib is also a protein tyrosine phosphatase ß (HPTPß) inhibitor.
| ln Vitro |
Razuprotafib (AKB-9778) increases angiopoietin-induced TIE2 phosphorylation and stimulates TIE2 phosphorylation and downstream signaling in HUVECs [1].
|
|---|---|
| ln Vivo |
Subcutaneous injection of razuprotafib (20 mg/kg) stimulates TIE2 phosphorylation in retinal endothelial cells in vivo [1]. Subretinal neovascularization (NV) is inhibited by razuprotafib (10–20 mg/kg; subcutaneous injection; twice daily for 7 days) [1].
|
| References | |
| Additional Infomation |
Razuprotafib, also known as AKB-9778, is a small-molecule inhibitor restoring Tie2 activation by inhibiting VE-PTP. In investigations against diabetes and COVID-19, razuprotafib is self-administered by patients through subcutaneous injection.
Razuprotafib is a small molecule inhibitor of vascular endothelial protein tyrosine phosphatase (VE-PTP), with potential vasculature stabilizing activity. Upon administration, razuprotafib targets, binds to and inhibits VE-PTP, which is a negative regulator of the endothelial cell (EC)-specific receptor tyrosine kinase (RTK) Tie2. This restores Tie2 activation, which may improve endothelial function and stabilize blood vessels. VE-PTP is upregulated in stressed endothelium associated with a variety of diseases. Tie2 plays an important role in endothelial function and vascular stability. A decrease in Tie2 activation leads to vascular leakage and inflammation. Mechanism of Action Razuprotafib inhibits [VE-PTP](https://go.drugbank.com/bio_entities/BE0003769) (a negative regulator of Tie2 in diseased blood vessels) by binding and inhibiting the intracellular catalytic domain of VE-PTP that inactivates Tie2. This in turn allows razuprotafib to restore Tie2 activation to allow for enhancement of endothelial function and stabilization of blood vessels. Razuprotafib is being investigated against diabetic vascular complications and acute respiratory distress syndrome (ARDS) in COVID-19. |
| Molecular Formula |
C26H26N4O6S3
|
|---|---|
| Molecular Weight |
586.702842235565
|
| Exact Mass |
586.101
|
| CAS # |
1008510-37-9
|
| Related CAS # |
1809275-69-1 (sodium);1008510-37-9;
|
| PubChem CID |
46700782
|
| Appearance |
White to off-white solid powder
|
| Density |
1.5±0.1 g/cm3
|
| Index of Refraction |
1.667
|
| LogP |
4.02
|
| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
10
|
| Rotatable Bond Count |
12
|
| Heavy Atom Count |
39
|
| Complexity |
906
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
COC(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC2=CC=C(C=C2)NS(=O)(=O)O)C3=CSC(=N3)C4=CC=CS4
|
| InChi Key |
KWJDHELCGJFUHW-SFTDATJTSA-N
|
| InChi Code |
InChI=1S/C26H26N4O6S3/c1-36-26(32)29-21(15-17-6-3-2-4-7-17)24(31)27-20(22-16-38-25(28-22)23-8-5-13-37-23)14-18-9-11-19(12-10-18)30-39(33,34)35/h2-13,16,20-21,30H,14-15H2,1H3,(H,27,31)(H,29,32)(H,33,34,35)/t20-,21-/m0/s1
|
| Chemical Name |
N-(4-{(2S)-2-{(2S)-2-[(methoxycarbonyl)amino]-3-phenylpropanamido}-2-[2-(thiophen-2-yl)-1,3-thiazol-4-yl]ethyl}phenyl)sulfamic acid
|
| Synonyms |
AKB-9778 AKB 9778 AKB9778
|
| 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 |
| 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) |
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
|
|---|---|
| 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 | 1.7044 mL | 8.5222 mL | 17.0445 mL | |
| 5 mM | 0.3409 mL | 1.7044 mL | 3.4089 mL | |
| 10 mM | 0.1704 mL | 0.8522 mL | 1.7044 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
