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

Identification

Generic Name
R-348
DrugBank Accession Number
DB06321
Background

Not Available

Type
Small Molecule
Groups
Investigational
Structure
Thumb
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

Pharmacology

Indication

Investigated for use/treatment in autoimmune diseases.

Pharmacology
Reduce drug development failure rates
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Contraindications & Blackbox Warnings
Contraindications
Avoid life-threatening adverse drug events
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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
Adverseeffects
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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

Clinical Trials
PhaseStatusPurposeConditionsCount

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
Not Available

Targets

Drugtargets2
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Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Protein tyrosine kinase activity
Specific 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...
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