This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.
Explore a selection of our essential drug information below, or:
Identification
- Generic Name
- Razuprotafib
- DrugBank Accession Number
- DB16353
- Background
Razuprotafib, also known as AKB-9778, is a small-molecule inhibitor restoring Tie2 activation by inhibiting VE-PTP.1,2 In investigations against diabetes and COVID-19, razuprotafib is self-administered by patients through subcutaneous injection.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
Structure for Razuprotafib (DB16353)
- Weight
- Average: 586.7
Monoisotopic: 586.101448095 - Chemical Formula
- C26H26N4O6S3
- Synonyms
- Razuprotafib
- External IDs
- AKB-9778
- WHO 10271
Pharmacology
- Indication
Not Available
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Not Available
- Mechanism of action
Razuprotafib inhibits VE-PTP (a negative regulator of Tie2 in diseased blood vessels) by binding and inhibiting the intracellular catalytic domain of VE-PTP that inactivates Tie2.1 This in turn allows razuprotafib to restore Tie2 activation to allow for enhancement of endothelial function and stabilization of blood vessels.2 Razuprotafib is being investigated against diabetic vascular complications and acute respiratory distress syndrome (ARDS) in COVID-19.
Target Actions Organism AReceptor-type tyrosine-protein phosphatase beta inhibitorHumans AAngiopoietin-1 receptor activatorHumans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- Not Available
Categories
- Drug Categories
- Classification
- Not classified
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 0WAX4UT396
- CAS number
- 1008510-37-9
- InChI Key
- KWJDHELCGJFUHW-SFTDATJTSA-N
- InChI
- 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
- IUPAC 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
- SMILES
- COC(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CC=C(NS(O)(=O)=O)C=C1)C1=CSC(=N1)C1=CC=CS1
References
- General References
- External Links
- ChemSpider
- 59718647
- ChEMBL
- CHEMBL3931971
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample data2 Completed Treatment Diabetic Macular Edema (DME) 1 somestatus stop reason just information to hide 2 Completed Treatment NPDR - Non Proliferative Diabetic Retinopathy 1 somestatus stop reason just information to hide 2 Completed Treatment Ocular Hypertension / Ocular Hypertension, Primary Open-angle Glaucoma (POAG) 1 somestatus stop reason just information to hide 2 Completed Treatment Retinal Vein Occlusion 1 somestatus stop reason just information to hide 2 Terminated Treatment Acute Respiratory Distress Syndrome (ARDS) / Coronavirus Disease 2019 (COVID‑19) 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Not Available
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.00482 mg/mL ALOGPS logP 2.64 ALOGPS logP 1.65 Chemaxon logS -5.1 ALOGPS pKa (Strongest Acidic) -1.4 Chemaxon pKa (Strongest Basic) 1.22 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 6 Chemaxon Hydrogen Donor Count 4 Chemaxon Polar Surface Area 146.72 Å2 Chemaxon Rotatable Bond Count 11 Chemaxon Refractivity 157.23 m3·mol-1 Chemaxon Polarizability 58.89 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Plays an important role in blood vessel remodeling and angiogenesis. Not necessary for the initial formation of blood vessels, but is essential for their maintenance and remodeling. Can induce dephosphorylation of TEK/TIE2, CDH5/VE-cadherin and KDR/VEGFR-2. Regulates angiopoietin-TIE2 signaling in endothelial cells. Acts as a negative regulator of TIE2, and controls TIE2 driven endothelial cell proliferation, which in turn affects blood vessel remodeling during embryonic development and determines blood vessel size during perinatal growth. Essential for the maintenance of endothelial cell contact integrity and for the adhesive function of VE-cadherin in endothelial cells and this requires the presence of plakoglobin (By similarity)
- Specific Function
- cadherin binding
- Gene Name
- PTPRB
- Uniprot ID
- P23467
- Uniprot Name
- Receptor-type tyrosine-protein phosphatase beta
- Molecular Weight
- 224299.74 Da
References
- Aerpio Pharmaceuticals: Razuprotafib (AKB-9778) Diabetic Nephropathy [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Activator
- General Function
- Tyrosine-protein kinase that acts as a cell-surface receptor for ANGPT1, ANGPT2 and ANGPT4 and regulates angiogenesis, endothelial cell survival, proliferation, migration, adhesion and cell spreading, reorganization of the actin cytoskeleton, but also maintenance of vascular quiescence. Has anti-inflammatory effects by preventing the leakage of pro-inflammatory plasma proteins and leukocytes from blood vessels. Required for normal angiogenesis and heart development during embryogenesis. Required for post-natal hematopoiesis. After birth, activates or inhibits angiogenesis, depending on the context. Inhibits angiogenesis and promotes vascular stability in quiescent vessels, where endothelial cells have tight contacts. In quiescent vessels, ANGPT1 oligomers recruit TEK to cell-cell contacts, forming complexes with TEK molecules from adjoining cells, and this leads to preferential activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascades. In migrating endothelial cells that lack cell-cell adhesions, ANGT1 recruits TEK to contacts with the extracellular matrix, leading to the formation of focal adhesion complexes, activation of PTK2/FAK and of the downstream kinases MAPK1/ERK2 and MAPK3/ERK1, and ultimately to the stimulation of sprouting angiogenesis. ANGPT1 signaling triggers receptor dimerization and autophosphorylation at specific tyrosine residues that then serve as binding sites for scaffold proteins and effectors. Signaling is modulated by ANGPT2 that has lower affinity for TEK, can promote TEK autophosphorylation in the absence of ANGPT1, but inhibits ANGPT1-mediated signaling by competing for the same binding site. Signaling is also modulated by formation of heterodimers with TIE1, and by proteolytic processing that gives rise to a soluble TEK extracellular domain. The soluble extracellular domain modulates signaling by functioning as decoy receptor for angiopoietins. TEK phosphorylates DOK2, GRB7, GRB14, PIK3R1; SHC1 and TIE1
- Specific Function
- ATP binding
- Gene Name
- TEK
- Uniprot ID
- Q02763
- Uniprot Name
- Angiopoietin-1 receptor
- Molecular Weight
- 125829.005 Da
References
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
Drug created at December 15, 2020 22:05 / Updated at August 26, 2024 19:23