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Details

Stereochemistry ACHIRAL
Molecular Formula C24H26N6O2S
Molecular Weight 462.567
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CEP-33779

SMILES

CN1CCN(CC1)C2=CC=CC(NC3=NN4C=CC=C(C4=N3)C5=CC=C(C=C5)S(C)(=O)=O)=C2

InChI

InChIKey=RFZKSQIFOZZIAQ-UHFFFAOYSA-N
InChI=1S/C24H26N6O2S/c1-28-13-15-29(16-14-28)20-6-3-5-19(17-20)25-24-26-23-22(7-4-12-30(23)27-24)18-8-10-21(11-9-18)33(2,31)32/h3-12,17H,13-16H2,1-2H3,(H,25,27)

HIDE SMILES / InChI

Molecular Formula C24H26N6O2S
Molecular Weight 462.567
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/22594690 | https://www.ncbi.nlm.nih.gov/pubmed/21880982 |

CEP-33779 is a selective JAK2 inhibitor (IC50 of 1.8 nM) developed by Cephalon, Inc for treating autoimmune disease (rheumatoid arthritis, lupus nephritis) and cancer. CEP-33779 orally administrated with 55 mg/kg inhibits phosphorylation of STAT5 in HEL92 tumor extracts from HEL92 xenograft mice. CEP33779 orally administered twice daily at the dose of 55 mg/kg reduces mean paw edema and clinical scores in mice with collagen-antibody-induced arthritis (CAIA) or collagen-induced arthritis (CIA). CEP-33779 orally administered twice daily at the dose of 55 mg/kg totally inhibits paw phospho-STAT3 expression in CAIA or CIA mice, associated with decreased cytokines including IL-12, IFNγ, IL-2, IL-1β, TNFα, and GM-CSF. CEP33779 results in reduced bone degradation, reduced tissue destruction, and reduced osteoarthritis in a dose-dependent manner in CAIA or CIA mice. CEP33779 orally administrated at 100 mg/kg extends survival and reduces splenomegaly/lymphomegaly in MRL/lpr systemic lupus erythematosus mice, thus protect mice from developing glomerulonephritis. CEP-33779 orally administrated at 100 mg/kg decreases several SLE-associated proinflammatory cytokines and reduces levels of a bone resorption biomarker associated with increased osteoclast activity in MRL/lpr systemic lupus erythematosus mice. CEP33779 orally administered twice daily at the dose of 55 mg/kg induces regression of established colorectal tumors, reduces angiogenesis, and reduces proliferation of tumor cells in a mouse model of colitis-induced colorectal cancer. Tumor regression correlated with inhibition of STAT3 and NF-κB (RelA/p65) activation, and decreased the expression of proinflammatory, tumor-promoting cytokines interleukin (IL)-6 and IL-1β

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
81.0 nM [IC50]
1.8 nM [IC50]
150.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
A selective, orally bioavailable 1,2,4-triazolo[1,5-a]pyridine-based inhibitor of Janus kinase 2 for use in anticancer therapy: discovery of CEP-33779.
2012 Jun 14
Patents

Patents

Sample Use Guides

Collagen antibody-induced arthritis (CAIA) and collagen type II (CII)-induced arthritis (CIA) were established before the oral administration of a small-molecule JAK2 inhibitor, CEP-33779, twice daily at 10 mg/kg, 30 mg/kg, 55 mg/kg or 100 mg/kg over a period of 4 to 8 weeks. Pharmacodynamic inhibition of JAK2 reduced mean paw edema and clinical scores in both CIA and CAIA models of arthritis.
Route of Administration: Oral
HEL92 cells were treated with increasing concentrations of CEP-33779 (0.01-3mkM)for 1 hour in serum-free media. Extracts were prepared in a Triton X-100-based lysis buffer, protein concentrations were determined, and equal amounts were resolved on sodium dodecyl sulfate polyacrylamide electrophoresis (SDS-PAGE) gels and blotted. STAT5 and pSTAT5 were analyzed using specific antibodies. CEP33779(< 3 μM) inhibits phosphorylation of downstream target signal transducer and activator of transcription 5(pSTAT5) of JAK2 in a concentration dependent manner in HEL92 cells.
Substance Class Chemical
Created
by admin
on Sat Dec 16 20:01:18 GMT 2023
Edited
by admin
on Sat Dec 16 20:01:18 GMT 2023
Record UNII
TE2YU6E6YP
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
CEP-33779
Common Name English
CEP33779
Common Name English
[1,2,4]Triazolo[1,5-a]pyridin-2-amine, N-[3-(4-methyl-1-piperazinyl)phenyl]-8-[4-(methylsulfonyl)phenyl]-
Systematic Name English
N-[3-(4-Methyl-1-piperazinyl)phenyl]-8-[4-(methylsulfonyl)phenyl][1,2,4]triazolo[1,5-a]pyridin-2-amine
Systematic Name English
[8-(4-Methylsulfonylphenyl)[1,2,4]triazolo[1,5-a]pyridin-2-yl][3-(4-methylpiperazin-1-yl)phenyl]amine
Systematic Name English
Code System Code Type Description
FDA UNII
TE2YU6E6YP
Created by admin on Sat Dec 16 20:01:18 GMT 2023 , Edited by admin on Sat Dec 16 20:01:18 GMT 2023
PRIMARY
CAS
1257704-57-6
Created by admin on Sat Dec 16 20:01:18 GMT 2023 , Edited by admin on Sat Dec 16 20:01:18 GMT 2023
PRIMARY
PUBCHEM
57336812
Created by admin on Sat Dec 16 20:01:18 GMT 2023 , Edited by admin on Sat Dec 16 20:01:18 GMT 2023
PRIMARY
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