PKC412

• CAT Number: I000769
• CAS Number: 120685-11-2
• Molecular Formula: C₃₅H₃₀N₄O₄
• Molecular Weight: 570.64
• Purity: ≥95%
• Target: PKC
• Solubility: DMSO: ≥ 34 mg/mL
• Storage: Store at -20°C
• InChI: InChI=1S/C35H30N4O4/c1-35-32(42-3)25(37(2)34(41)19-11-5-4-6-12-19)17-26(43-35)38-23-15-9-7-13-20(23)28-29-22(18-36-33(29)40)27-21-14-8-10-16-24(21)39(35)31(27)30(28)38/h4-16,25-26,32H,17-18H2,1-3H3,(H,36,40)/t25-,26-,32-,35+/m1/s1
• InChIKey: BMGQWWVMWDBQGC-IIFHNQTCSA-N
• SMILES: CC12C(C(CC(O1)N3C4=CC=CC=C4C5=C6C(=C7C8=CC=CC=C8N2C7=C53)CNC6=O)N(C)C(=O)C9=CC=CC=C9)OC

Midostaurin（Cat No.:I000769）, also known as PKC412 or CGP 41251, is a potent multi-target kinase inhibitor. It exhibits inhibitory activity against several kinases including PKCα/β/γ, Syk, Flk-1, Akt, PKA, c-Kit, c-Fgr, c-Src, FLT3, PDFRβ, and VEGFR1/2. The half-maximal inhibitory concentration (IC50) ranges from 80 to 500 nM for these targets. By targeting multiple kinases, midostaurin has the potential to interfere with various signaling pathways involved in cellular proliferation, angiogenesis, and survival. It has been investigated for its therapeutic potential in treating various cancers and other diseases where these kinases play a critical role.

Reference

1:Pre-clinical characterization of PKC412, a multi-kinase inhibitor, against colorectal cancer cells. Li JP, Huang ZJ, Lu XS, Zhou YC, Shao Y, He XP, Chen SR, Wang DD, Qin LS, Sun WH.Oncotarget. 2016 Nov 22;7(47):77815-77824. doi: 10.18632/oncotarget.12802. PMID: 27780925 Free PMC Article2:Activation of HIV-1 expression in latently infected CD4+ T cells by the small molecule PKC412. Ao Z, Zhu R, Tan X, Liu L, Chen L, Liu S, Yao X.Virol J. 2016 Oct 21;13(1):177. PMID: 27769267 Free PMC Article3:PKC412 normalizes mutation-related keratin filament disruption and hepatic injury in mice by promoting keratin-myosin binding. Kwan R, Chen L, Looi K, Tao GZ, Weerasinghe SV, Snider NT, Conti MA, Adelstein RS, Xie Q, Omary MB.Hepatology. 2015 Dec;62(6):1858-69. doi: 10.1002/hep.27965. Epub 2015 Aug 25. PMID: 26126491 Free PMC Article4:The DNA Methyltransferase DNMT1 and Tyrosine-Protein Kinase KIT Cooperatively Promote Resistance to 5-Aza-2/’-deoxycytidine (Decitabine) and Midostaurin (PKC412) in Lung Cancer Cells. Yan F, Shen N, Pang J, Molina JR, Yang P, Liu S.J Biol Chem. 2015 Jul 24;290(30):18480-94. doi: 10.1074/jbc.M114.633693. Epub 2015 Jun 17. PMID: 26085088 Free PMC Article5:The structure of a dual-specificity tyrosine phosphorylation-regulated kinase 1A-PKC412 complex reveals disulfide-bridge formation with the anomalous catalytic loop HRD(HCD) cysteine. Alexeeva M, Åberg E, Engh RA, Rothweiler U.Acta Crystallogr D Biol Crystallogr. 2015 May;71(Pt 5):1207-15. doi: 10.1107/S1399004715005106. Epub 2015 Apr 25. PMID: 25945585 6:Phase I/II trial of the combination of midostaurin (PKC412) and 5-azacytidine for patients with acute myeloid leukemia and myelodysplastic syndrome. Strati P, Kantarjian H, Ravandi F, Nazha A, Borthakur G, Daver N, Kadia T, Estrov Z, Garcia-Manero G, Konopleva M, Rajkhowa T, Durand M, Andreeff M, Levis M, Cortes J.Am J Hematol. 2015 Apr;90(4):276-81. doi: 10.1002/ajh.23924. Epub 2015 Mar 2. PMID: 25530214 Free PMC Article7:Familial systemic mastocytosis with germline KIT K509I mutation is sensitive to treatment with imatinib, dasatinib and PKC412. de Melo Campos P, Machado-Neto JA, Scopim-Ribeiro R, Visconte V, Tabarroki A, Duarte AS, Barra FF, Vassalo J, Rogers HJ, Lorand-Metze I, Tiu RV, Costa FF, Olalla Saad ST, Traina F.Leuk Res. 2014 Oct;38(10):1245-51. doi: 10.1016/j.leukres.2014.07.010. Epub 2014 Aug 1. PMID: 25139846 Free Article8:Mast cell leukemia with prolonged survival on PKC412/midostaurin. Xu X, Kreisel FH, Frater JL, Hassan A.Int J Clin Exp Pathol. 2014 May 15;7(6):3439-43. eCollection 2014. PMID: 25031773 Free PMC Article9:Preclinical and phase I results of decitabine in combination with midostaurin (PKC412) for newly diagnosed elderly or relapsed/refractory adult patients with acute myeloid leukemia. Williams CB, Kambhampati S, Fiskus W, Wick J, Dutreix C, Ganguly S, Aljitawi O, Reyes R, Fleming A, Abhyankar S, Bhalla KN, McGuirk JP.Pharmacotherapy. 2013 Dec;33(12):1341-52. doi: 10.1002/phar.1316. Epub 2013 Jun 24. PMID: 23798029 10:Synergistic growth-inhibitory effects of ponatinib and midostaurin (PKC412) on neoplastic mast cells carrying KIT D816V. Gleixner KV, Peter B, Blatt K, Suppan V, Reiter A, Radia D, Hadzijusufovic E, Valent P.Haematologica. 2013 Sep;98(9):1450-7. doi: 10.3324/haematol.2012.079202. Epub 2013 Mar 28. PMID: 23539538 Free PMC Article