1. Epigenetics
    Stem Cell/Wnt
    JAK/STAT Signaling
    Protein Tyrosine Kinase/RTK
  2. JAK
    Syk

Cerdulatinib (Synonyms: PRT062070; PRT2070)

Cat. No.: HY-15999 Purity: 97.44%
Data Sheet SDS Handling Instructions

Cerdulatinib is a novel, orally available, ATP-competitive inhibitor that demonstrates selective inhibition of SYK and JAK kinases with IC50 of 32 nM for SYK and 0.5-12 nM for JAKs.

For research use only. We do not sell to patients.
Cerdulatinib Chemical Structure

Cerdulatinib Chemical Structure

CAS No. : 1198300-79-6

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  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

Cerdulatinib is a novel, orally available, ATP-competitive inhibitor that demonstrates selective inhibition of SYK and JAK kinases with IC50 of 32 nM for SYK and 0.5-12 nM for JAKs.

IC50 & Target

IC50: 32 nM (SYK), 0.5-12 nM (JAKs)[1], 12 nM (JAK1)[3]

In Vitro

Cerdulatinib shows inhibitory effect on 60 CLL with IC50 ranging from 0.37 to 10.02 µM. Cerdulatinib induces apoptosis in CLL in association with MCL-1 down-regulation and PARP cleavage. Cerdulatinib (2μM) is able to overcome the support of the microenvironment and induces CLL cell death. Cerdulatinib (250-500 nM) blocks proliferation of ibrutinib-sensitive and ibrutinib-resistant primary CLL cells. Cerdulatinib also blocks proliferation of both ibrutinib-sensitive and ibrutinib-resistant primary CLL cells as well as BTKC481S-transfected cell lines, and blocks BCR and JAK-STAT signaling pathways. Furthermore, inhibition of SYK and JAK by cerdulatinib translates to downstream inhibition of AKT and ERK. Cerdulatinib inhibits the activity of NF-kB pathway[1]. PRT062070 reduces the ability of stimulated B cells to upregulate cell-surface expression of the early activation marker CD69 (IC50=0.11 µM). PRT062070 exhibits differential potency against cytokine JAK/STAT signaling pathways. PRT062070 (1 or 3 µM) induces apoptosis in BCR-signaling competent NHL cell lines[2]. Cerdulatinib demonstrates inhibitory activity against both ABC and GCB subtypes of DLBCL cells. Cerdulatinib also induces apoptosis in both GCB and ABC subtypes of DLBCL cell lines via caspase 3 and PARP cleavage. And cerdulatinib blocks cell cycle in both ABC and GCB subtypes of DLBCL via inhibition of RB phosphorylation and down-regulation of cyclin E. Cerdulatinib induces cell cycle arrest and apoptosis under the condition of BCR stimulation in all DLBCL cell lines. Besides, cerdulatinib blocks JAK/STAT and BCR signaling in both ABC and GCB DLBCL cell lines. Cerdulatinib induces cell death in primary human DLBCL samples[3]. Cerdulatinib inhibits BCR-induced signals in a dose-dependent manner and most strongly between 0.3 to 1 μM. and particularly in IGHV-unmutated samples with greater BCR signaling capacity and response to IL4, or samples expressing higher levels of sIgM, CD49d+, or ZAP70+. Cerdulatinib overcomes anti-IgM, IL4/CD40L, or NLC-mediated protection by preventing upregulation of MCL-1 and BCL-XL; however, BCL-2 expression is unaffected. Furthermore, in samples treated with IL4/CD40L, cerdulatinib synergizes with venetoclax in vitro to induce greater apoptosis than either drug alone[4].

In Vivo

PRT062070 (0.5 mg/kg) results in a nonstatistically significant trend toward reduced ankle inflammation, whereas significant reductions in inflammation are achieved with the 1.5, 3, and 5 mg/kg doses. PRT062070 also affects anticollagen antibody formation. PRT062070 (15 mg/kg) suppresses upregulation of splenic B-cell surface CD80/86 and CD69, and inhibits BCR signaling and activation in the spleen after oral dosing in mice[2].

Clinical Trial
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References
Preparing Stock Solutions
Concentration Volume Mass 1 mg 5 mg 10 mg
1 mM 2.2445 mL 11.2223 mL 22.4447 mL
5 mM 0.4489 mL 2.2445 mL 4.4889 mL
10 mM 0.2244 mL 1.1222 mL 2.2445 mL
Please refer to the solubility information to select the appropriate solvent.
Cell Assay
[1]

Cerdulatinib is dissolved in DMSO.

TMD8 cells are transfected with constructs of WT BTK or BTKC481S mutants using kit V, Program U-13 on Amaxa Nucleofector. After transfection, the cells are co-cultured with NKTert cells in a 24-well plate for 24 hrs for recovery. Ibrutinib, cerdulatinib and vehicle (DMSO) are then added into the transfected TMD8 cells and cellular viability is determined with MuseTM Count & Viability kit using Muse Cell Analyzer. The cell survival is determined by flow cytometry using the Annexin V/7-AAD Apoptosis Detection Kit I on freshly isolated CLL cells. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

445.54

Formula

C₂₀H₂₇N₇O₃S

CAS No.

1198300-79-6

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

DMSO: ≥ 30 mg/mL

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

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Cerdulatinib
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