product name CEP-33779
Description: CEP33779 is a orally active, highly selective JAK2 inhibitor with IC50 of 1.8 nM, >40- and >800-fold versus JAK1 and TYK2. It induced regression of established colorectal tumors, reduced angiogenesis, and reduced proliferation of tumor cells. The ability of CEP-33779 to suppress growth of colorectal tumors by inhibiting the IL-6/JAK2/STAT3 signaling suggests a potential therapeutic utility of JAK2 inhibitors in multiple tumors types, particularly those with a strong inflammatory component.
References: Arthritis Res Ther. 2011 Apr 21;13(2):R68; J Immunol. 2011 Oct 1;187(7):3840-53; Mol Cancer Ther. 2012 Apr;11(4):984-93.
462.57
Formula
C24H26N6O2S
CAS No.
1257704-57-6
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 93 mg/mL (201.1 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
1% DMSO+30% polyethylene glycol+1% Tween 80: 30 mg/mL
Synonyms
other peoduct :
| In Vitro |
In vitro activity: 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. Kinase Assay: CEP-33779 is a novel, selective, and orally bioavailable inhibitor of JAK2 with IC50 of 1.8 nM. Cell Assay: In a cellular system, CEP-33779 is shown to inhibit JAK2 in irf-bla TF-1 cells utilizing the GeneBLAzer reporter assay. It is also able to mitigate several immune parameters associated with SLE advancement, including the protection and treatment of mice with lupus nephritis. The ability of CEP-33779 to suppress growth of colorectal tumors by inhibiting the IL-6/JAK2/STAT3 signaling suggests a potential therapeutic utility of JAK2 inhibitors in multiple tumors types, particularly those with a strong inflammatory component. |
|---|---|
| In Vivo | CEP33779 orally administrated with 55 mg/kg inhibits phosphorylation of STAT5 in HEL92 tumor extracts from HEL92 xenograft mice. CEP33779 orally administered twice daily at 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). CEP33779 orally administered twice daily at 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 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. CEP33779 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 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. |
| Animal model | Mice with collagen-induced arthritis (CIA) and collagen-antibody induced arthritis (CAIA) |
| Formulation & Dosage | Dissolved in DMSO; 55 mg/kg; Oral administration |
| References | Arthritis Res Ther. 2011 Apr 21;13(2):R68; J Immunol. 2011 Oct 1;187(7):3840-53; Mol Cancer Ther. 2012 Apr;11(4):984-93. |
