Cerdulatinib free base
featured

    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.


Chemical Structure

img
Cerdulatinib free base
CAS# 1198300-79-6 (free base)

Theoretical Analysis

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

Price and Availability

Size Price Availability Quantity
10.0mg USD 150.0 Same day
25.0mg USD 250.0 Same day
50.0mg USD 450.0 Same day
100.0mg USD 650.0 Same day
200.0mg USD 850.0 Same day
500.0mg USD 1650.0 Same day
1.0g USD 2450.0 2 Weeks
2.0g USD 4150.0 2 Weeks
5.0g USD 6450.0 2 Weeks
Click to view more sizes and prices
Bulk inquiry

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

Solubility Data

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

Preparing Stock Solutions

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.

Recalculate based on batch purity %
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.

Molarity Calculator

Calculate the mass, volume, or concentration required for a solution.
=
x
x
g/mol

*When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and SDS / CoA (available online).

Reconstitution Calculator

The reconstitution calculator allows you to quickly calculate the volume of a reagent to reconstitute your vial. Simply enter the mass of reagent and the target concentration and the calculator will determine the rest.

=
÷

Dilution Calculator

Calculate the dilution required to prepare a stock solution.
x
=
x

1: Oh J, O'Connor PW. An update of teriflunomide for treatment of multiple sclerosis. Ther Clin Risk Manag. 2013;9:177-90. doi: 10.2147/TCRM.S30947. Epub 2013 Apr 26. PubMed PMID: 23761970.

2: Oh J, O'Connor PW. Teriflunomide for the treatment of multiple sclerosis. Semin Neurol. 2013 Feb;33(1):45-55. doi: 10.1055/s-0033-1343795. Epub 2013 May 25. PubMed PMID: 23709212.

3: Warnke C, Meyer Zu Hörste G, Menge T, Stüve O, Hartung HP, Wiendl H, Kieseier BC. [Teriflunomide for treatment of multiple sclerosis]. Nervenarzt. 2013 Jun;84(6):724-31. doi: 10.1007/s00115-013-3779-7. German. PubMed PMID: 23695001.

4: Wiese MD, Rowland A, Polasek TM, Sorich MJ, O'Doherty C. Pharmacokinetic evaluation of teriflunomide for the treatment of multiple sclerosis. Expert Opin Drug Metab Toxicol. 2013 May 17. [Epub ahead of print] PubMed PMID: 23682862.

5: Tanasescu R, Evangelou N, Constantinescu CS. Role of oral teriflunomide in the management of multiple sclerosis. Neuropsychiatr Dis Treat. 2013;9:539-53. doi: 10.2147/NDT.S31248. Epub 2013 Apr 22. PubMed PMID: 23637535; PubMed Central PMCID: PMC3639219.

6: Hussar DA, Hurrey NJ. Aclidinium bromide, tofacitinib citrate, and teriflunomide. J Am Pharm Assoc (2003). 2013 Jan 1;53(1):106-10. doi: 10.1331/JAPhA.2013.13504. PubMed PMID: 23636164.

7: Xi H, Cun D, Xiang R, Guan Y, Zhang Y, Li Y, Fang L. Intra-articular drug delivery from an optimized topical patch containing teriflunomide and lornoxicam for rheumatoid arthritis treatment: Does the topical patch really enhance a local treatment? J Control Release. 2013 Apr 6;169(1-2):73-81. doi: 10.1016/j.jconrel.2013.03.028. [Epub ahead of print] PubMed PMID: 23567043.

8: Wolinsky JS, Narayana PA, Nelson F, Datta S, O'Connor P, Confavreux C, Comi G, Kappos L, Olsson TP, Truffinet P, Wang L, Miller A, Freedman MS; for the Teriflunomide Multiple Sclerosis Oral (TEMSO) Trial Group. Magnetic resonance imaging outcomes from a phase III trial of teriflunomide. Mult Scler. 2013 Feb 27. [Epub ahead of print] PubMed PMID: 23447359.

9: He D, Xu Z, Dong S, Zhang H, Zhou H, Wang L, Zhang S. Teriflunomide for multiple sclerosis. Cochrane Database Syst Rev. 2012 Dec 12;12:CD009882. doi: 10.1002/14651858.CD009882.pub2. Review. PubMed PMID: 23235682.

10: Papadopoulou A, Kappos L, Sprenger T. Teriflunomide for oral therapy in multiple sclerosis. Expert Rev Clin Pharmacol. 2012 Nov;5(6):617-28. doi: 10.1586/ecp.12.56. PubMed PMID: 23234322.



Additional Information