Cerdulatinib

Cerdulatinib is a dual inhibitor of spleen tyrosine kinase (Syk) and Janus kinases (JAK, IC50s = 32, 12, 6, 8, and 0.5 nM for Syk, JAK1, JAK2, JAK3, and TYK2, respectively) and also exhibits nanomolar inhibition of other kinases. Syk is involved in the B cell receptor (BCR) pathway, and cerdulatinib inhibits downstream Syk-mediated signaling of ERK Y204 phosphorylation (IC50 = 0.5 µM), upregulates cell surface expression of CD69 (IC50 = 0.11 µM), and inhibits FcepsilonRI-mediated basophil degranulation (IC50 = 0.12 µM). JAK is involved in JAK-STAT regulation of cytokine receptors. Cerdulatinib inhibits STAT3, STAT5, and STAT6 phosphorylation by interleukin-activated JAK1/3 with IC50 values ranging from 0.16 to 1 µM. Cerdulatinib disrupts JAK1/3-mediated signaling more selectively than JAK2 signaling (IC50 > 4 µM). Cerdulatinib displays potent antitumor activity against ABC and GCB types of diffuse large B cell lymphoma (DLBCL) by inducing apoptosis via caspase-2 and poly(ADP-ribose) polymerase (PARP) cleavage. Cerdulatinib exhibits IC50 values ranging from 0.05 to 2.1 µM against a panel of DLBCL tumor cell lines.Formal Name: 4-(cyclopropylamino)-2-[[4-[4-(ethylsulfonyl)-1-piperazinyl]phenyl]amino]-5-pyrimidinecarboxamide. CAS Number: 1198300-79-6. Synonyms: PRT062070, PRT2070. Molecular Formula: C20H27N7O3S. Formula Weight: 445.5. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 20 mg/ml, DMSO: 20 mg/ml, DMSO:PBS(pH 7.2) (1:3): 0.25 mg/ml. lambdamax: 233, 285, 328 nm. SMILES: CCS(N1CCN(C2=CC=C(NC3=NC(NC4CC4)=C(C(N)=O)C=N3)C=C2)CC1)(=O)=O. 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). InChi Key: BGLPECHZZQDNCD-UHFFFAOYSA-N.