The inhibitory impact of cerulelatinib ranges from 0.37 to 10.02 µM on 60 CLL. Cerdulatinib promotes apoptosis in CLL in conjunction with PARP breakage and MCL-1 down-regulation. Cerdulatinib (2µM) can cause CLL cell death by overriding the microenvironment's support. Primary CLL cells that are both ibrutinib-sensitive and -resistant are prevented from proliferating by cerulelatinib (250–500 nM). In addition, ceruleanib inhibits the growth of BTKC481S-transfected cell lines, ibrutinib-sensitive and ibrutinib-resistant primary CLL cells, as well as the BCR and JAK-STAT signaling pathways. Moreover, cerdulatinib's suppression of SYK and JAK results in the downstream inhibition of ERK and AKT. The NF-kB pathway is inhibited by cerulelatinib[1]. The early activation marker CD69's (IC50=0.11 µM) capacity to increase its cell-surface expression is diminished by PRT062070 in activated B cells. Differential efficacy against cytokine JAK/STAT signaling pathways is demonstrated by PRT062070. BCR-signaling competent NHL cell lines undergo apoptosis when exposed to 1 or 3 µM of PRT062070[2]. Cerdulatinib exhibits inhibitory action against DLBCL cells of both the ABC and GCB classes. Through caspase 3 and PARP cleavage, ceruleanib also causes apoptosis in the DLBCL cell lines belonging to the GCB and ABC classes. Additionally, cerdulatinib inhibits the cell cycle in the DLBCL ABC and GCB subtypes by downregulating cyclin E and RB phosphorylation. In all DLBCL cell lines, ceruleaninb causes apoptosis and cell cycle arrest in response to BCR stimulation. Moreover, cerdulatinib inhibits BCR and JAK/STAT signaling in GCB DLBCL and ABC cell lines. Cerdulatinib causes primary human DLBCL samples to undergo cell death[3]. In a dose-dependent manner, cerulelatinib mostly suppresses BCR-induced signals between 0.3 and 1 μM. and especially in IGHV-unmutated samples that express larger levels of sIgM, CD49d+, or ZAP70+, or that have stronger BCR signaling capacity and responsiveness to IL4. By inhibiting the induction of MCL-1 and BCL-XL, cerulelatinib circumvents the protective effects of anti-IgM, IL4/CD40L, or NLC; BCL-2 expression remains unchanged. Moreover, cerdulatinib and venetoclax work together in vitro to elicit more apoptosis in samples treated with IL4/CD40L than either medication alone[4].

While there is a nonstatistically significant trend toward decreased ankle inflammation with PRT062070 (0.5 mg/kg), the 1.5, 3, and 5 mg/kg doses result in significant reductions in inflammation. The production of anticollagen antibodies is impacted by PRT062070. Following oral administration in mice, PRT062070 (15 mg/kg) inhibits BCR signaling and activation in the spleen and suppresses upregulation of splenic B-cell surface CD80/86 and CD69[2].

[1]. Guo A, 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, 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]. Ma J, et al. 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.
[4]. Blunt MD, et al. 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

C20H27N7O3S

445.54

1198300-79-6

Cerdulatinib hydrochloride;1369761-01-2

O=C(C1=CN=C(NC2=CC=C(N3CCN(S(=O)(CC)=O)CC3)C=C2)N=C1NC4CC4)N

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.61 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (5.61 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)