R343
Explore a selection of our essential drug information below, or:
Identification
- Generic Name
- R343
- DrugBank Accession Number
- DB06316
- Background
R343, was investigated in clinical trial NCT01591044 to evaluate its safety and efficacy in patients with mild to moderate asthma.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
- Weight
- Average: 474.4
Monoisotopic: 474.12633754 - Chemical Formula
- C21H17F3N6O4
- Synonyms
- 2- {3- [4-(2,2-Difluoro-3 -oxo-3,4-dihydro-2H-benzo [1,4] oxazin-6-ylamino)5-fluoro-pyrimidin-2-ylamino]phenoxy}N-methyl-acetamide
- External IDs
- R-940343
- R940343
Pharmacology
- Indication
Investigated for use/treatment in allergic reaction and asthma.
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
R343 is a syk kinase inhibitor. Syk kinase is a protein tyrosine kinase that plays a pivotal role in high affinity IgE receptor signaling in mast cells. Syk kinase inhibitors bind to syk in mast cells interrupting the signal from the Immunoglobulin E (IgE receptor), thus preventing cellular activation and subsequent chemical mediator release, and potentially blocking an allergic response in allergic asthma. Allergic asthma is a chronic inflammatory disorder of the airways whereby persistent inflammation of the airway passages results in airway obstruction. In some patients, allergens, such as pollen, trigger the production of immunoglobulin E antibodies (IgE antibodies) which then bind to mast cells and cause an intracellular signal that results in the release of various chemical mediators. [Rigel Pharmaceuticals Press Release]
Target Actions Organism UTyrosine-protein kinase SYK 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
- 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
- Not Available
- Classification
- Not classified
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- Y4069R7J86
- CAS number
- 575484-78-5
- InChI Key
- MOXXQFNQDDSJHT-UHFFFAOYSA-N
- InChI
- InChI=1S/C21H17F3N6O4/c1-25-17(31)10-33-13-4-2-3-11(7-13)28-20-26-9-14(22)18(30-20)27-12-5-6-16-15(8-12)29-19(32)21(23,24)34-16/h2-9H,10H2,1H3,(H,25,31)(H,29,32)(H2,26,27,28,30)
- IUPAC Name
- SMILES
- CNC(=O)COC1=CC=CC(NC2=NC=C(F)C(NC3=CC=C4OC(F)(F)C(=O)NC4=C3)=N2)=C1
References
- General References
- Link [Link]
- External Links
- ChemSpider
- 8520278
- BindingDB
- 50396071
- ChEMBL
- CHEMBL2170582
- ZINC
- ZINC000038576002
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 Asthma 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
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Not Available
- Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Targets
![](/assets/locked/DrugTargets2-1d1d534575da54e734c316d80c9fb35f8210c070dca913c026f8e58660e3e71a.png)
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Non-receptor tyrosine kinase which mediates signal transduction downstream of a variety of transmembrane receptors including classical immunoreceptors like the B-cell receptor (BCR). Regulates several biological processes including innate and adaptive immunity, cell adhesion, osteoclast maturation, platelet activation and vascular development (PubMed:12387735, PubMed:33782605). Assembles into signaling complexes with activated receptors at the plasma membrane via interaction between its SH2 domains and the receptor tyrosine-phosphorylated ITAM domains. The association with the receptor can also be indirect and mediated by adapter proteins containing ITAM or partial hemITAM domains. The phosphorylation of the ITAM domains is generally mediated by SRC subfamily kinases upon engagement of the receptor. More rarely signal transduction via SYK could be ITAM-independent. Direct downstream effectors phosphorylated by SYK include DEPTOR, VAV1, PLCG1, PI-3-kinase, LCP2 and BLNK (PubMed:12456653, PubMed:15388330, PubMed:34634301, PubMed:8657103). Initially identified as essential in B-cell receptor (BCR) signaling, it is necessary for the maturation of B-cells most probably at the pro-B to pre-B transition (PubMed:12456653). Activated upon BCR engagement, it phosphorylates and activates BLNK an adapter linking the activated BCR to downstream signaling adapters and effectors. It also phosphorylates and activates PLCG1 and the PKC signaling pathway. It also phosphorylates BTK and regulates its activity in B-cell antigen receptor (BCR)-coupled signaling. In addition to its function downstream of BCR also plays a role in T-cell receptor signaling. Plays also a crucial role in the innate immune response to fungal, bacterial and viral pathogens. It is for instance activated by the membrane lectin CLEC7A. Upon stimulation by fungal proteins, CLEC7A together with SYK activates immune cells inducing the production of ROS. Also activates the inflammasome and NF-kappa-B-mediated transcription of chemokines and cytokines in presence of pathogens. Regulates neutrophil degranulation and phagocytosis through activation of the MAPK signaling cascade (By similarity). Required for the stimulation of neutrophil phagocytosis by IL15 (PubMed:15123770). Also mediates the activation of dendritic cells by cell necrosis stimuli. Also involved in mast cells activation. Involved in interleukin-3/IL3-mediated signaling pathway in basophils (By similarity). Also functions downstream of receptors mediating cell adhesion (PubMed:12387735). Relays for instance, integrin-mediated neutrophils and macrophages activation and P-selectin receptor/SELPG-mediated recruitment of leukocytes to inflammatory loci. Also plays a role in non-immune processes. It is for instance involved in vascular development where it may regulate blood and lymphatic vascular separation. It is also required for osteoclast development and function. Functions in the activation of platelets by collagen, mediating PLCG2 phosphorylation and activation. May be coupled to the collagen receptor by the ITAM domain-containing FCER1G. Also activated by the membrane lectin CLEC1B that is required for activation of platelets by PDPN/podoplanin. Involved in platelet adhesion being activated by ITGB3 engaged by fibrinogen. Together with CEACAM20, enhances production of the cytokine CXCL8/IL-8 via the NFKB pathway and may thus have a role in the intestinal immune response (By similarity)
- Specific Function
- Atp binding
- Gene Name
- SYK
- Uniprot ID
- P43405
- Uniprot Name
- Tyrosine-protein kinase SYK
- Molecular Weight
- 72065.76 Da
Drug created at March 19, 2008 16:24 / Updated at July 31, 2024 09:44