WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 206113
CAS#: 1198300-79-6 (free base)
Description: Cerdulatinib, also known as PRT2070 and PRT062070, is a n ovel, oral, dual spleen tyrosine kinase (Syk) and janus kinase (JAK) inhibitor. Cerdulatinib preferentially inhibited JAK1 and JAK3 dependent cytokine mediated signaling and functional responses in various cell types. IL2 mediated STAT5 Y694 was inhibited with an IC50 of 0.27μM, while IL4 mediated signaling to STAT6 Y641 and functional responses in B cells and monocytes, namely CD69, CD25, and CD23 up-regulation, were inhibited with IC50Â’s within the range of 0.11μM to 0.57μM. It is currently being studied in patients with genetically-defined hematologic cancers, as well as for patients who have failed therapy due to relapse or acquired mutations.
MedKoo Cat#: 206113
Name: Cerdulatinib free base
CAS#: 1198300-79-6 (free base)
Chemical Formula: C20H27N7O3S
Exact Mass: 445.18961
Molecular Weight: 445.54
Elemental Analysis: C, 53.92; H, 6.11; N, 22.01; O, 10.77; S, 7.20
Related CAS #: 1198300-79-6 (free base) 1369761-01-2 (HCl)
Synonym: PRT2070; PRT-2070; PRT 2070; PRT062070; PRT 062070; PRT-062070; Cerdulatinib.
IUPAC/Chemical Name: 4-(cyclopropylamino)-2-((4-(4-(ethylsulfonyl)piperazin-1-yl)phenyl)amino)pyrimidine-5-carboxamide
InChi Key: BGLPECHZZQDNCD-UHFFFAOYSA-N
InChi Code: InChI=1S/C20H27N7O3S/c1-2-31(29,30)27-11-9-26(10-12-27)16-7-5-15(6-8-16)24-20-22-13-17(18(21)28)19(25-20)23-14-3-4-14/h5-8,13-14H,2-4,9-12H2,1H3,(H2,21,28)(H2,22,23,24,25)
SMILES Code: O=C(C1=CN=C(NC2=CC=C(N3CCN(S(=O)(CC)=O)CC3)C=C2)N=C1NC4CC4)N
Appearance: white solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | Cerdulatinib (PRT062070) is a selective Tyk2 inhibitor with an IC50 of 0.5 nM. |
| In vitro activity: | In order to determine whether cerdulatinib is effective against CLL in the presence of microenvironmental support, this study first tested the effects of cerdulatinib in two in vitro CLL co-culture models mimicking the in vivo microenvironment. Addition of 2μM cerdulatinib significantly reduced CLL cell viability throughout the 7-day course, even when cells were co-cultured over either NKTert or HS-5, human bone marrow stromal cell lines (Figure 3A). The anti-survival effect became more pronounced as the dose of cerdulatinib was escalated from 1 to 4 uM with both models (Figure 3B). Reference: Oncotarget. 2017 Feb 21; 8(8): 12953–12967. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355069/ |
| In vivo activity: | This study tested the potential for PRT062070 to modulate inflammation in the rat CIA treatment model after oral dosing. Animals treated with vehicle control exhibited a rapid onset of hind paw inflammation within 2–3 days of boosting with adjuvant, with maximal inflammation occurring by day 7. Treatment with 0.5 mg/kg PRT062070 (attaining average Cmax plasma concentration at 2 hours of 0.18 µM) resulted in a nonstatistically significant trend toward reduced ankle inflammation, whereas significant reductions in inflammation were achieved with the 1.5, 3, and 5 mg/kg doses, with average Cmax plasma concentrations at 2 hours of 0.52, 0.58, and 1.49 µM, respectively. Inflammation was abolished at the 3 mg/kg dose and reversed relative to pretreatment levels at 5 mg/kg (Fig. 6A). Significant improvements in inflammatory infiltrate within the synovium and the integrity of the articular cartilage were observed in a dose-dependent manner (Fig. 6B). Representative histologic evaluations are shown in Supplemental Fig. 3. Reference: J Pharmacol Exp Ther. 2014 Dec;351(3):538-48. https://jpet.aspetjournals.org/content/351/3/538.long |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 25.0 | 56.11 | |
| DMSO:PBS (pH 7.2) (1:3) | 0.25 | 0.56 | |
| DMF | 20.0 | 44.89 |
The following data is based on the product molecular weight 445.54 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Guo A, Lu P, Coffey G, Conley P, Pandey A, Wang YL. 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. doi: 10.18632/oncotarget.14588. PMID: 28088788; PMCID: PMC5355069. 2. 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. 3. Coffey G, Betz A, DeGuzman F, Pak Y, Inagaki M, Baker DC, Hollenbach SJ, Pandey A, Sinha U. 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. doi: 10.1124/jpet.114.218164. Epub 2014 Sep 24. PMID: 25253883. |
| In vitro protocol: | 1. Guo A, Lu P, Coffey G, Conley P, Pandey A, Wang YL. 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. doi: 10.18632/oncotarget.14588. PMID: 28088788; PMCID: PMC5355069. 2. 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. |
| In vivo protocol: | 1. Coffey G, Betz A, DeGuzman F, Pak Y, Inagaki M, Baker DC, Hollenbach SJ, Pandey A, Sinha U. 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. doi: 10.1124/jpet.114.218164. Epub 2014 Sep 24. PMID: 25253883. |
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