CRx-119
Identification
- Generic Name
- CRx-119
- DrugBank Accession Number
- DB05688
- Background
CRx-119 is a novel synergistic combination drug candidate discovered using the CombinatoRx combination High Throughput Screening (cHTS(TM)) technology with potential therapeutic use in a broad range of immuno-inflammatory conditions. CRx-119 is a combination of a low dose of the steroid prednisolone, 3mg, and amoxapine.
- Type
- Small Molecule
- Groups
- Investigational
- Synonyms
- Not Available
Pharmacology
- Indication
Investigated for use/treatment in periodontal disease and rheumatoid arthritis.
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- Pharmacodynamics
CRx-119 is a novel orally available syncretic drug candidate in clinical development for immunoinflammatory diseases. A syncretic drug comprises two compounds that are designed to act together synergistically through multiple pathways to provide a novel therapeutic effect which neither component alone can achieve. CRx-119 contains a low dose of the steroid prednisolone and amoxapine. The target product profile for CRx-119 is to selectively amplify certain elements of prednisolone's anti-inflammatory and immunomodulatory effects, without replicating steroid toxicity.
- Mechanism of action
Amoxapine acts by decreasing the reuptake of norepinephrine and serotonin (5-HT). Glucocorticoids such as prednisolone can inhibit leukocyte infiltration at the site of inflammation, interfere with mediators of inflammatory response, and suppress humoral immune responses. The antiinflammatory actions of glucocorticoids are thought to involve phospholipase A2 inhibitory proteins, lipocortins, which control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes. Prednisolone reduces inflammatory reaction by limiting the capillary dilatation and permeability of the vascular structures. These compounds restrict the accumulation of polymorphonuclear leukocytes and macrophages and reduce the release of vasoactive kinins. Recent research suggests that corticosteroids may inhibit the release of arachidonic acid from phospholipids, thereby reducing the formation of prostaglandins. Prednisolone is a glucocorticoid receptor agonist. On binding, the corticoreceptor-ligand complex translocates itself into the cell nucleus, where it binds to many glucocorticoid response elements (GRE) in the promoter region of the target genes. The DNA bound receptor then interacts with basic transcription factors, causing an increase or decrease in expression of specific target genes, including suppression of IL2 (interleukin 2) expression.
Target Actions Organism USodium-dependent serotonin transporter Not Available Humans USodium-dependent noradrenaline transporter Not Available Humans - 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
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- Toxicity
CRx-119 was generally well tolerated and there were no drug-related serious adverse events reported. The most common adverse event observed with CRx-119 was drowsiness, a known side-effect of amoxapine.
- 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
- Not Available
- Classification
- Not classified
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- Not Available
- CAS number
- Not Available
- InChI Key
- Not Available
- InChI
- Not Available
- IUPAC Name
- Not Available
- SMILES
- Not Available
References
- General References
- Not Available
- External Links
- PubChem Substance
- 347910193
Clinical Trials
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
- Not Available
- Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Not Available
- Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Serotonin:sodium symporter activity
- Specific Function
- Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into t...
- Gene Name
- SLC6A4
- Uniprot ID
- P31645
- Uniprot Name
- Sodium-dependent serotonin transporter
- Molecular Weight
- 70324.165 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Norepinephrine:sodium symporter activity
- Specific Function
- Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.
- Gene Name
- SLC6A2
- Uniprot ID
- P23975
- Uniprot Name
- Sodium-dependent noradrenaline transporter
- Molecular Weight
- 69331.42 Da
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Steroid binding
- Specific Function
- Major transport protein for glucocorticoids and progestins in the blood of almost all vertebrate species.
- Gene Name
- SERPINA6
- Uniprot ID
- P08185
- Uniprot Name
- Corticosteroid-binding globulin
- Molecular Weight
- 45140.49 Da
Drug created at November 18, 2007 18:27 / Updated at June 12, 2020 16:52