Midostaurin is an organic protein kinase inhibitor for tyrosine kinase, protein kinase C, and VEGF. It is an organic heterooctacyclic compound that is the N-benzoyl derivative of stauroporine, an alkaloid from Streptomyces staurosporeus. It has been studied for its potential use for acute myeloid leukemia, myelodysplastic syndrome, and systemic mastocytosis. Midostaurin is an inhibitor of FLT3 activation loop mutations. It can be used in cancer research and has anti-tumor properties. The compound is used in COVID-19 research in repurposing studies to target the SARS-CoV-2 Main protease. Midostaurin is soluble in DMSO.
|Midostaurin is active against fungi and protozoa. It has no antibacterial activity.
|Mechanism of Action
Midostaurin is a small molecule that inhibits multiple receptor tyrosine kinases. Midostaurin and its major active metabolites inhibit the activity of protein kinase C alpha (PKCalpha), VEGFR2, KIT, PDGFR and WT and/or mutant TLT3.
|Eukaryotic Cell Culture Applications
Midostaurin inhibits the growth of various human and animal cell lines in vitro. It inhibits in vitro proliferation of glioblastoma. Midostaurin can reverse the p-glycoprotein-mediated multidrug resistance of tumor cells in vitro.
Midostatin is an antineoplastic agent and has antiproliferative activity toward multiple cancer cell ines.
Midostatin blocks the transport of ATP-binding cassette (ABC) protein ABCB1 and re-sensitizes ABCB1-overexpressing multidrug-resistant cancer cells to conventional chemotherapeutic compounds. Midostaurin potentiates drug-induced apoptosis in ABCB1-overexpressing cancer cells and inhibits the ATPase activity of ABCB1. This means that multidrug-resistant tumors may benefit from Midostaurin coupled with standard chemotherapeutic agents (Hsiao et al, 2019).
Midostatin can inhibit growth; induce megakaryocytic differentiation; and to a lesser extent, cause apoptosis in human erythroleukemia (HEL) cells (Huang Y et al, 2009)
Gupta A and Zhou HX (2020) Profiling SARS-CoV-2 Main protease (MPRO) Binding to repurposed drugs using molecular dynamics simulations in classical and neural network-trained force fields. ACS Comb Sci. 22(12):826-832.PMID 33119257
Huang Y, CHao D, Chao CKC adn Chen Y (2009) Oral small-molecule tyrosine kinase inhibitor Midostaurin (PKC412) inhibits growth and induces megakaryocytic differentiation in human leukemia cells. Toxicol. In VItro 23(6):979-985 PMID 19573588
Hsiao S et al (2019) The FLT3 inhibitor midostaurin selectively resensitizes ABCB1-overexpressing multidrug-resistant cancer cells to conventional chemotherapeutic agents. Cancer Lett. 445:34-44 PMID 30639533
Jacobs CF, Eldering E and Kater AP (2021) Kinase inhibitors developed for treatment of hematologic malignancies: Implications for immune modulation in COVID-19. Blood Adv. 5(3):913-925 PMID 33560402