Cerdulatinib free base
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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

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Cerdulatinib free base
CAS# 1198300-79-6 (free base)
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 206113
Name: Cerdulatinib free base
CAS#: 1198300-79-6 (free base)
Chemical Formula: C20H27N7O3S
Exact Mass: 445.19
Molecular Weight: 445.540
Elemental Analysis: C, 53.92; H, 6.11; N, 22.01; O, 10.77; S, 7.20

Price and Availability

Size Price Availability Quantity
10mg USD 150 Ready to ship
25mg USD 300 Ready to ship
50mg USD 500 Ready to ship
100mg USD 850 Ready to ship
200mg USD 1450 Ready to ship
500mg USD 2650 Ready to ship
5mg USD 90 Ready to ship
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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

Product Data:
Product Data
Instruction:
View handling instruction
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) 0.3 0.56
DMF 20.0 44.89

Preparing Stock Solutions

The following data is based on the product molecular weight 445.540000000000000000000000000000 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.

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1: Traidl S, Freimooser S, Werfel T. Janus kinase inhibitors for the therapy of atopic dermatitis. Allergol Select. 2021 Aug 27;5:293-304. doi: 10.5414/ALX02272E. PMID: 34532638; PMCID: PMC8439108. 2: Montilla AM, Gómez-García F, Gómez-Arias PJ, Gay-Mimbrera J, Hernández-Parada J, Isla-Tejera B, Ruano J. Scoping Review on the Use of Drugs Targeting JAK/STAT Pathway in Atopic Dermatitis, Vitiligo, and Alopecia Areata. Dermatol Ther (Heidelb). 2019 Dec;9(4):655-683. doi: 10.1007/s13555-019-00329-y. Epub 2019 Oct 13. PMID: 31606872; PMCID: PMC6828894. 3: Coffey GP, Feng J, Betz A, Pandey A, Birrell M, Leeds JM, Der K, Kadri S, Lu P, Segal J, Wang YL, Michelson G, Curnutte JT, Conley PB. Cerdulatinib Pharmacodynamics and Relationships to Tumor Response Following Oral Dosing in Patients with Relapsed/Refractory B-cell Malignancies. Clin Cancer Res. 2019 Feb 15;25(4):1174-1184. doi: 10.1158/1078-0432.CCR-18-1047. Epub 2018 Oct 17. PMID: 30333224. 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: Tang S, Yu Q, Ding C. Investigational spleen tyrosine kinase (SYK) inhibitors for the treatment of autoimmune diseases. Expert Opin Investig Drugs. 2022 Mar;31(3):291-303. doi: 10.1080/13543784.2022.2040014. Epub 2022 Feb 18. PMID: 35130124. 6: Ishikawa C, Senba M, Mori N. Anti-adult T‑cell leukemia/lymphoma activity of cerdulatinib, a dual SYK/JAK kinase inhibitor. Int J Oncol. 2018 Oct;53(4):1681-1690. doi: 10.3892/ijo.2018.4513. Epub 2018 Aug 1. PMID: 30066853. 7: Szalus K, Trzeciak M, Nowicki RJ. JAK-STAT Inhibitors in Atopic Dermatitis from Pathogenesis to Clinical Trials Results. Microorganisms. 2020 Nov 6;8(11):1743. doi: 10.3390/microorganisms8111743. PMID: 33172122; PMCID: PMC7694787. 8: 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. 9: Piscitelli SC, Pavel AB, McHale K, Jett JE, Collins J, Gillmor D, Tabolt G, Li R, Song T, Zhang N, Tallman AM, Guttman-Yassky E. A Phase 1b, Randomized, Single-Center Trial of Topical Cerdulatinib (DMVT-502) in Patients with Mild-to- Moderate Atopic Dermatitis. J Invest Dermatol. 2021 Jul;141(7):1847-1851. doi: 10.1016/j.jid.2020.11.031. Epub 2021 Jan 22. PMID: 33493530. 10: Sadeghi S, Mohandesi NA. Efficacy and safety of topical JAK inhibitors in the treatment of atopic dermatitis in paediatrics and adults: A systematic review. Exp Dermatol. 2023 May;32(5):599-610. doi: 10.1111/exd.14753. Epub 2023 Feb 3. PMID: 36691705. 11: 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. 12: 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. 13: Hamlin PA, Flinn IW, Wagner-Johnston N, Burger JA, Coffey GP, Conley PB, Michelson G, Leeds JM, Der K, Kim Y, Sabalvaro-Torres A, Birrell M, Pandey A, Curnutte JT, Patel MR. Efficacy and safety of the dual SYK/JAK inhibitor cerdulatinib in patients with relapsed or refractory B-cell malignancies: Results of a phase I study. Am J Hematol. 2019 Apr;94(4):E90-E93. doi: 10.1002/ajh.25387. Epub 2019 Jan 8. PMID: 30592080. 14: Tavakoli Shirazi P, Eadie LN, Page EC, Heatley SL, Bruning JB, White DL. Constitutive JAK/STAT signaling is the primary mechanism of resistance to JAKi in TYK2-rearranged acute lymphoblastic leukemia. Cancer Lett. 2021 Aug 1;512:28-37. doi: 10.1016/j.canlet.2021.04.027. Epub 2021 May 7. PMID: 33971281. 15: Liu D, Mamorska-Dyga A. Syk inhibitors in clinical development for hematological malignancies. J Hematol Oncol. 2017 Jul 28;10(1):145. doi: 10.1186/s13045-017-0512-1. PMID: 28754125; PMCID: PMC5534090. 16: Munera-Campos M, Carrascosa JM. Janus Kinase Inhibitors in Atopic Dermatitis: New Perspectives. Actas Dermosifiliogr. 2023 Apr 25:S0001-7310(23)00323-X. English, Spanish. doi: 10.1016/j.ad.2023.04.025. Epub ahead of print. PMID: 37105270. 17: Deshpande A, Munoz J. Targeted and cellular therapies in lymphoma: Mechanisms of escape and innovative strategies. Front Oncol. 2022 Sep 12;12:948513. doi: 10.3389/fonc.2022.948513. PMID: 36172151; PMCID: PMC9510896. 18: Mónica MC, Manuel CJ. [[Translated article]]Janus Kinase Inhibitors in Atopic Dermatitis: New Perspectives. Actas Dermosifiliogr. 2023 Jul 13:S0001-7310(23)00579-3. English, Spanish. doi: 10.1016/j.ad.2023.07.006. Epub ahead of print. PMID: 37453538. 19: Ji TT, Chen QN, Tao SD, Yu L. [Research Advance on the Role of Spleen Tyrosine Kinase Inhibitors in Hematologic Malignancies]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2020 Jun;28(3):1054-1058. Chinese. doi: 10.19746/j.cnki.issn.1009-2137.2020.03.056. PMID: 32552981. 20: Brattås MK, Hemsing AL, Rye KP, Hatfield KJ, Reikvam H. Heterogeneity of Patient-Derived Acute Myeloid Leukemia Cells Subjected to SYK In Vitro Inhibition. Int J Mol Sci. 2022 Nov 25;23(23):14706. doi: 10.3390/ijms232314706. PMID: 36499034; PMCID: PMC9737311.