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R-348

This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

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Identification

Generic Name
R-348
DrugBank Accession Number
DB06321
Background

Not Available

Type
Small Molecule
Groups
Investigational
Structure
3D
Similar Structures
Weight
Average: 483.52
Monoisotopic: 483.137653545
Chemical Formula
C23H22FN5O4S
Synonyms
  • 5-Fluoro-N-(4-methyl-3-propionylaminosulfonylphenyl)-N'-(4-(prop-2-ynyloxy)phenyl)-2,4-pyrimidinediamine
External IDs
  • R 348
  • R-348
  • R348
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Pharmacology

Indication

Investigated for use/treatment in autoimmune diseases.

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Contraindications & Blackbox Warnings
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Pharmacodynamics

Not Available

Mechanism of action

R438 is a selective Janus tyrosine kinase 3 (JAK3) inhibitor prodrug which is converted to its active metabolite R333. JAKs are cytoplasmic tyrosine kinases that are involved in immune system activation and cytokine signaling. They achieve their effects when coupled with signal tranducers and activators of transcription (STATs). JAK3 is critical to immune system activation, and high levels of JAK3 are expressed in cells and thyocytes, and are inducible in T and B cells. JAK3 is also found in nonhematopoietic cells, but its function in these cells is currently undetermined. JAK3 inhibitors impede the development of CD8 memory cells by attenuating the interleukin 7 (IL7) and interleukin 15 (IL-15) pathways, making it a promising drug for treatment of autoimmune disorders.

TargetActionsOrganism
UTyrosine-protein kinase JAK3Not AvailableHumans
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

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
3J396119JY
CAS number
916742-11-5
InChI Key
IGLNXKVGKIFNBQ-UHFFFAOYSA-N
InChI
InChI=1S/C23H22FN5O4S/c1-4-12-33-18-10-8-16(9-11-18)26-22-19(24)14-25-23(28-22)27-17-7-6-15(3)20(13-17)34(31,32)29-21(30)5-2/h1,6-11,13-14H,5,12H2,2-3H3,(H,29,30)(H2,25,26,27,28)
IUPAC Name
N-{5-[(5-fluoro-4-{[4-(prop-2-yn-1-yloxy)phenyl]amino}pyrimidin-2-yl)amino]-2-methylbenzenesulfonyl}propanamide
SMILES
CCC(=O)NS(=O)(=O)C1=CC(NC2=NC=C(F)C(NC3=CC=C(OCC#C)C=C3)=N2)=CC=C1C

References

General References
  1. Deuse T, Velotta JB, Hoyt G, Govaert JA, Taylor V, Masuda E, Herlaar E, Park G, Carroll D, Pelletier MP, Robbins RC, Schrepfer S: Novel immunosuppression: R348, a JAK3- and Syk-inhibitor attenuates acute cardiac allograft rejection. Transplantation. 2008 Mar 27;85(6):885-92. doi: 10.1097/TP.0b013e318166acc4. [Article]
ChemSpider
58828170
ZINC
ZINC000115724111

Clinical Trials

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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
PropertyValueSource
Water Solubility0.00263 mg/mLALOGPS
logP3.84ALOGPS
logP4.22Chemaxon
logS-5.3ALOGPS
pKa (Strongest Acidic)4.24Chemaxon
pKa (Strongest Basic)1.9Chemaxon
Physiological Charge-1Chemaxon
Hydrogen Acceptor Count8Chemaxon
Hydrogen Donor Count3Chemaxon
Polar Surface Area122.31 Å2Chemaxon
Rotatable Bond Count8Chemaxon
Refractivity125.61 m3·mol-1Chemaxon
Polarizability48.82 Å3Chemaxon
Number of Rings3Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-03di-0000900000-0eca94bbc1bd7a9b71a3
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-00fr-0010900000-7192366cc176b6463e1a
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-03di-0009800000-038894803dcce49e1fda
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-00di-1000900000-1b1120886513f3f4fdec
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a5c-0029300000-f9bb08ff18ac15917fe1
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-053i-0129100000-98d24066d25e75417f92
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
Not Available

Targets

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Details1. Tyrosine-protein kinase JAK3
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Non-receptor tyrosine kinase involved in various processes such as cell growth, development, or differentiation. Mediates essential signaling events in both innate and adaptive immunity and plays a crucial role in hematopoiesis during T-cells development. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. Following ligand binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins. Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. For example, upon IL2R activation by IL2, JAK1 and JAK3 molecules bind to IL2R beta (IL2RB) and gamma chain (IL2RG) subunits inducing the tyrosine phosphorylation of both receptor subunits on their cytoplasmic domain. Then, STAT5A and STAT5B are recruited, phosphorylated and activated by JAK1 and JAK3. Once activated, dimerized STAT5 translocates to the nucleus and promotes the transcription of specific target genes in a cytokine-specific fashion
Specific Function
Atp binding
Gene Name
JAK3
Uniprot ID
P52333
Uniprot Name
Tyrosine-protein kinase JAK3
Molecular Weight
125097.565 Da
References
  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [Article]

Drug created at March 19, 2008 16:24 / Updated at June 12, 2020 16:52