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Chemical Structure| 1198300-79-6 Chemical Structure| 1198300-79-6

Structure of Cerdulatinib
CAS No.: 1198300-79-6

Chemical Structure| 1198300-79-6

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Cerdulatinib (PRT062070) is an effective and selective Tyk2 inhibitor with an IC50 of 0.5 nM. It is a dual inhibitor of JAK and SYK, with IC50 values of 12, 6, 8, and 32 nM against JAK1, JAK2, JAK3, and SYK, respectively.

Synonyms: PRT062070; PRT2070

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Product Details of Cerdulatinib

CAS No. :1198300-79-6
Formula : C20H27N7O3S
M.W : 445.54
SMILES Code : O=C(C1=CN=C(NC2=CC=C(N3CCN(S(=O)(CC)=O)CC3)C=C2)N=C1NC4CC4)N
Synonyms :
PRT062070; PRT2070
MDL No. :N/A
InChI Key :BGLPECHZZQDNCD-UHFFFAOYSA-N
Pubchem ID :44595079

Safety of Cerdulatinib

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Related Pathways of Cerdulatinib

epigenetics
RTK
JAK-STAT

Isoform Comparison

Biological Activity

Target
  • JAK1

    JAK1, IC50:12 nM

  • JAK3

    JAK3, IC50:8 nM

  • Tyk2

    TYK2, IC50:0.5 nM

  • JAK2

    JAK2, IC50:6 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
A549 cells 5 μM 1 h Inhibit IFN receptor signaling, thereby inhibiting the antiviral activity of RSV-EVs PMC9412241
CLL cells (IGHV unmutated samples) 0.003-3µM 48 h To assess the ability of Cerdulatinib to kill CLL cells with different prognostic markers, results showed that IGHV unmutated, CD49d+ or ZAP70+ expressing CLL samples were more sensitive to drug-induced killing. PMC5417366
Chronic lymphocytic leukemia (CLL) cells 0.003-3µM 24, 48 or 72 h To evaluate the effect of Cerdulatinib on CLL cell viability, results showed that Cerdulatinib reduced CLL cell viability in a concentration and time-dependent manner, and increased caspase 3 activity and PARP cleavage. PMC5417366
H1299 cells 1 μM 24 h Inhibited TYK2 phosphorylation and reversed the promotion effect of RAB27A overexpression on cell proliferation, migration, and invasion PMC10960821
A549 cells 1 μM 24 h Inhibited TYK2 phosphorylation and reversed the promotion effect of RAB27A overexpression on cell proliferation, migration, and invasion PMC10960821
JVM2-UGT2B17OE 0.5 μM 24 h Evaluate the effect of cerdulatinib on the proliferation of UGT2B17-overexpressing cells, showing that cerdulatinib effectively compromised the proliferative advantage conferred by UGT2B17 PMC10177405
MEC1-UGT2B17OE 0.5 μM 24 h Evaluate the effect of cerdulatinib on the proliferation of UGT2B17-overexpressing cells, showing that cerdulatinib effectively compromised the proliferative advantage conferred by UGT2B17 PMC10177405

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
BALB/C nude mice A549 cell xenograft model Oral 35 mg/kg 5 days per week for 4 weeks Suppressed RAB27A-overexpression promoted tumor growth and metastasis PMC10960821

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT04021082 Peripheral T-Cell Lymphoma (PT... More >>CL NOS)|Nodal Lymphomas of T Follicular Helper (TFH)|Follicular T-cell Lymphoma (FTCL)|AITL|ALCL|HSTCL|EATL I,II|MEITL, EATL Type II|Nasal Lymphoma Less << PHASE2|PHASE3 WITHDRAWN 2023-06-01 -

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.24mL

0.45mL

0.22mL

11.22mL

2.24mL

1.12mL

22.44mL

4.49mL

2.24mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

[1]Guo A, Lu P, Coffey G, et al. Dual SYK/JAK inhibition overcomes ibrutinib resistance in chronic lymphocytic leukemia: Cerdulatinib, but not ibrutinib, induces apoptosis of tumor cells protected by the microenvironment. Oncotarget. 2017 Feb 21;8(8):12953-12967.

[2]Coffey G, Betz A, et al. The novel kinase inhibitor PRT062070 (Cerdulatinib) demonstrates efficacy in models of autoimmunity and B-cell cancer. J Pharmacol Exp Ther. 2014 Dec;351(3):538-48.

[3]Juillerat-Jeanneret L, Aubert JD, Mikulic J, Golshayan D. Fibrogenic Disorders in Human Diseases: From Inflammation to Organ Dysfunction. J Med Chem. 2018 Nov 21;61(22):9811-9840. doi: 10.1021/acs.jmedchem.8b00294. Epub 2018 Jul 17. PMID: 29969256.

[4]Ma J, Xing W, Coffey G, Dresser K, Lu K, Guo A, Raca G, Pandey A, Conley P, Yu H, Wang YL. Cerdulatinib, a novel dual SYK/JAK kinase inhibitor, has broad anti-tumor activity in both ABC and GCB types of diffuse large B cell lymphoma. Oncotarget. 2015 Dec 22;6(41):43881-96. doi: 10.18632/oncotarget.6316. PMID: 26575169; PMCID: PMC4791274.

[5]Blunt MD, Koehrer S, Dobson RC, Larrayoz M, Wilmore S, Hayman A, Parnell J, Smith LD, Davies A, Johnson PWM, Conley PB, Pandey A, Strefford JC, Stevenson FK, Packham G, Forconi F, Coffey GP, Burger JA, Steele AJ. The Dual Syk/JAK Inhibitor Cerdulatinib Antagonizes B-cell Receptor and Microenvironmental Signaling in Chronic Lymphocytic Leukemia. Clin Cancer Res. 2017 May 1;23(9):2313-2324. doi: 10.1158/1078-0432.CCR-16-1662. Epub 2016 Oct 3. PMID: 27697994; PMCID: PMC5417366.

 

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