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S5921 Sigma

Staurosporine from Streptomyces sp.

for molecular biology, ≥95% (HPLC)

Synonym: Antibiotic AM-2282

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Description

Frequently Asked Questions

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Analysis Note

Tested for inhibition of interleukin 2 production in Jurkat cells.

Biochem/physiol Actions

Potent inhibitor of phospholipid/calcium-dependent protein kinase. Inhibits the upregulation of VEGF expression in tumor cells.

Partially reverses MDR, sensitizing cells with MDR phenotype to cytotoxic agents. Inhibits Pgp phosphorylation. However, functional significance of Pgp phosphorylation is ill defined.

Application

Staurosporine from Streptomyces sp. was used to induce cell death in MDCK, 293T, Vero, HeLa, and Swiss Webster primary macrophage cells.5 It was used to study the effect of caspase activation on human sperm quality.6

Price and Availability

TruPAGE™ Pre-cast Polyacrylamide Gels


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Safety & Documentation

Safety Information

Symbol 
GHS08  GHS08
Signal word 
Danger
Hazard statements 
Precautionary statements 
Hazard Codes (Europe) 
T
Risk Statements (Europe) 
Safety Statements (Europe) 
53-45
WGK Germany 
3

Protocols & Articles

Articles

Discover Bioactive Small Molecules for ADME/Tox

A significant number of drugs that fail in clinical trials have been associated with safety issues, including unexpected drug-drug interactions (DDI) or lack of efficacy due to poor pharmacokinetics....
Keywords: Absorption, Bioactive small molecules, Clinical, Metabolism

Drug Transport

Protein-based drug transporters are found in most tissues including liver, kidney, intestine, and brain. Because of their complexity and genetic heterogeneity, these proteins are often produced as re...
Robert Gates
Biofiles Volume 6 Article 1
Keywords: Absorption, Anti-inflammatory agents, Antibiotics, Antimicrobials, Apoptosis, Cancer, Catalog, Cytotoxins, Detoxification, Enzyme-linked immunosorbent assay, Gene expression, Genetic, High performance liquid chromatography, Immunohistochemistry, Mass spectrometry, Metabolites, Methods, Phosphorylations, Separation, The Reporter, Transfection, Type, Western blot

Peer-Reviewed Papers

References

Set your institution to view full text papers.

A phase II study of UCN-01 in combination with irinotecan in patients with metastatic triple negative breast cancer. Ma CX, Ellis MJ, Petroni GR, et al. Breast Cancer Res. Treat. 137(2), 483-92, (2013)

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Anthraquinone-2-sulfonic acid (AQ2S) is a novel neurotherapeutic agent. Jackson TC, Verrier JD, and Kochanek PM Cell Death Dis. 4, e451, (2013)

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Comparison of staurosporine and four analogues: their effects on growth, rhodamine 123 retention and binding to P-glycoprotein in multidrug-resistant MCF-7/Adr cells. Budworth, J., et al. Br. J. Cancer 73, 1063, (1996)

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Fragmented inositol 1,4,5-trisphosphate receptors retain tetrameric architecture and form functional Ca2+ release channels. Alzayady KJ, Chandrasekhar R, and Yule DI J. Biol. Chem. 288(16), 11122-34, (2013)

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Exome sequencing identifies recurring FLT3 N676K mutations in core-binding factor leukemia. Opatz S, Polzer H, Herold T, et al. Blood 122(10), 1761-9, (2013)

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Automated classification and visualization of fluorescent live cell microscopy images. Urish KL, Deasy BM, and Huard J J. Microsc. 249(3), 206-14, (2013)

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Profilin 1 potentiates apoptosis induced by staurosporine in cancer cells. Yao W, Cai X, Liu C, et al. Curr. Mol. Med. 13(3), 417-28, (2013)

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Protein kinase C: a worthwhile target for anticancer drugs? Caponigro, F., et al. Anticancer Drugs 8, 26, (1997)

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K252a and staurosporine microbial alkaloid toxins as prototype of neurotropic drugs. Lazarovici P, Rasouly D, Friedman L, et al. Adv. Exp. Med. Biol. 391, 367-77, (1996)

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A rare mutation in UNC5C predisposes to late-onset Alzheimer's disease and increases neuronal cell death. Wetzel-Smith MK, Hunkapiller J, Bhangale TR, et al. Nat. Med. 20(12), 1452-7, (2014)

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Exploiting the cytoskeletal filaments of neoplastic cells to potentiate a novel therapeutic approach. Trendowski M Biochim. Biophys. Acta 1846(2), 599-616, (2014)

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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, et al. Leuk. Res. 38(10), 1245-51, (2014)

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[Systemic mastocytosis]. Metzgeroth G, Schwaab J, and Reiter A Dtsch. Med. Wochenschr. 139(31-32), 1572-5, (2014)

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Unconventional apoptosis of polymorphonuclear neutrophils (PMN): staurosporine delays exposure of phosphatidylserine and prevents phagocytosis by MΦ-2 macrophages of PMN. Franz S, Muñoz LE, Heyder P, et al. Clin. Exp. Immunol. 179(1), 75-84, (2015)

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Post-translational modification and mitochondrial relocalization of histone H3 during apoptosis induced by staurosporine. Han MJ, Koc EC, and Koc H Biochem. Biophys. Res. Commun. 450(1), 802-7, (2014)

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3D high-content screening for the identification of compounds that target cells in dormant tumor spheroid regions. Wenzel C, Riefke B, Gründemann S, et al. Exp. Cell Res. 323(1), 131-43, (2014)

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Combination therapy to reduce conjunctival scarring after glaucoma surgery. Zarbin MA JAMA Ophthalmol. 131(9), 1123, (2013)

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Arrestin-dependent but G-protein coupled receptor kinase-independent uncoupling of D2-dopamine receptors. Celver J, Sharma M, Thanawala V, et al. J. Neurochem. 127(1), 57-65, (2013)

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[Effects of alpha-tocopherol and its anologues on rat thymocytes programmed death induced by protein kinase inhibitors]. Petrova GV, Delemenchuk NV, and Donchenko GV Ukr. Biokhim. Zh. 84(6), 86-95, (2012)

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MicroRNA-31 sensitizes human breast cells to apoptosis by direct targeting of protein kinase C epsilon (PKCepsilon). Körner C, Keklikoglou I, Bender C, et al. J. Biol. Chem. 288(12), 8750-61, (2013)

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Inhibition of Ephrin B3-mediated survival signaling contributes to increased cell death response of non-small cell lung carcinoma cells after combined treatment with ionizing radiation and PKC 412. Ståhl S, Kaminskyy VO, Efazat G, et al. Cell Death Dis. 4, e454, (2013)

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Staurosporine: a prototype of a novel class of inhibitors of tumor cell invasion? O'Brian CA and Ward NE J. Natl. Cancer Inst. 82(22), 1734-5, (1990)

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Staurosporine, K-252 and UCN-01: potent but nonspecific inhibitors of protein kinases. Rüegg UT and Burgess GM Trends Pharmacol. Sci. 10(6), 218-20, (1989)

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Analogs of staurosporine: potential anticancer drugs? Gescher A Gen. Pharmacol. 31(5), 721-8, (1998)

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Dual inhibition of classical protein kinase C-α and protein kinase C-β isoforms protects against experimental murine diabetic nephropathy. Menne J, Shushakova N, Bartels J, et al. Diabetes 62(4), 1167-74, (2013)

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Absence of Nogo-B (reticulon 4B) facilitates hepatic stellate cell apoptosis and diminishes hepatic fibrosis in mice. Tashiro K, Satoh A, Utsumi T, et al. Am. J. Pathol. 182(3), 786-95, (2013)

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Protein kinase inhibition of clinically important staurosporine analogues. Gani OA and Engh RA Nat. Prod. Rep. 27(4), 489-98, (2010)

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The secondary FLT3-ITD F691L mutation induces resistance to AC220 in FLT3-ITD+ AML but retains in vitro sensitivity to PKC412 and Sunitinib. Albers C, Leischner H, Verbeek M, et al. Leukemia 27(6), 1416-8, (2013)

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Oncogenic activation of Pak1-dependent pathway of macropinocytosis determines BCG entry into bladder cancer cells. Redelman-Sidi G, Iyer G, Solit DB, et al. Cancer Res. 73(3), 1156-67, (2013)

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Apoptotic marker expression in the absence of cell death in staurosporine-treated Leishmania donovani. Foucher AL, Rachidi N, Gharbi S, et al. Antimicrob. Agents Chemother. 57(3), 1252-61, (2013)

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Clinical significance and novel mechanism of action of kallikrein 6 in glioblastoma. Drucker KL, Paulsen AR, Giannini C, et al. Neuro. Oncol. 15(3), 305-18, (2013)

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Matrix metalloproteinase (MMP)-1 induces lung alveolar epithelial cell migration and proliferation, protects from apoptosis, and represses mitochondrial oxygen consumption. Herrera I, Cisneros J, Maldonado M, et al. J. Biol. Chem. 288(36), 25964-75, (2013)

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In vitro approach to predict post-translational phosphorylation response to mixtures. Boyd J, Vrana JA, and Williams HN Toxicology 313(2-3), 113-21, (2013)

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High temporal resolution fluorescence measurements of a mitochondrial dye for detection of early stage apoptosis. Iyer D, Ray RD, and Pappas D Analyst 138(17), 4892-7, (2013)

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Protein kinase/phosphatase function correlates with gliding motility in Mycoplasma pneumoniae. Page CA and Krause DC J. Bacteriol. 195(8), 1750-7, (2013)

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Regulation of cytochrome P450 2e1 expression by ethanol: role of oxidative stress-mediated pkc/jnk/sp1 pathway. Jin M, Ande A, Kumar A, et al. Cell Death Dis. 4, e554, (2013)

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Flavivirus NS4A-induced autophagy protects cells against death and enhances virus replication. McLean, J.E., et al. J. Biol. Chem. 286, 22147-59, (2011)

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Proapoptotic chemotherapeutic drugs induce noncanonical processing and release of IL-1β via caspase-8 in dendritic cells. Antonopoulos C, El Sanadi C, Kaiser WJ, et al. J. Immunol. 191(9), 4789-803, (2013)

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Staurosporine analogues - pharmacological toys or useful antitumour agents? Gescher A Crit. Rev. Oncol. Hematol. 34(2), 127-35, (2000)

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Staurosporine, a potentially important gift from a microorganism. Omura S, Sasaki Y, Iwai Y, et al. J. Antibiot. 48(7), 535-48, (1995)

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Staurosporine is chemoprotective by inducing G1 arrest in a Chk1- and pRb-dependent manner. Murray MM, Bui T, Smith M, et al. Carcinogenesis 34(10), 2244-52, (2013)

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Role of cathepsin D in U18666A-induced neuronal cell death: potential implication in Niemann-Pick type C disease pathogenesis. Amritraj A, Wang Y, Revett TJ, et al. J. Biol. Chem. 288(5), 3136-52, (2013)

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Responsive microsecond-lifetime photoluminescent probes for analysis of protein kinases and their inhibitors. Kasari M, Ligi K, Williams JA, et al. Biochim. Biophys. Acta 1834(7), 1330-5, (2013)

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DDX3 regulates DNA damage-induced apoptosis and p53 stabilization. Sun M, Zhou T, Jonasch E, et al. Biochim. Biophys. Acta 1833(6), 1489-97, (2013)

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Perturbation of the mutated EGFR interactome identifies vulnerabilities and resistance mechanisms. Li J, Bennett K, Stukalov A, et al. Mol. Syst. Biol. 9, 705, (2013)

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Chemical biology of natural indolocarbazole products: 30 years since the discovery of staurosporine. Nakano H and Omura S J. Antibiot. 62(1), 17-26, (2009)

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RNA interference targeting sensitive-to-apoptosis gene potentiates doxorubicin- and staurosporine-induced apoptosis of PC3 cells. Yang ES, Huh YJ, and Park JW Anticancer Res. 33(3), 847-55, (2013)

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Membrane potential-dependent uptake of 18F-triphenylphosphonium--a new voltage sensor as an imaging agent for detecting burn-induced apoptosis. Zhao G, Yu YM, Shoup TM, et al. J. Surg. Res. 188(2), 473-9, (2014)

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Interference with the contractile machinery of the fibroblastic chondrocyte cytoskeleton induces re-expression of the cartilage phenotype through involvement of PI3K, PKC and MAPKs. Rottmar M, Mhanna R, Guimond-Lischer S, et al. Exp. Cell Res. 320(2), 175-87, (2014)

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Selective Akt inhibitors synergize with tyrosine kinase inhibitors and effectively override stroma-associated cytoprotection of mutant FLT3-positive AML cells. Weisberg E, Liu Q, Zhang X, et al. PLoS ONE 8(2), e56473, (2013)

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Staurosporine, a potent inhibitor of phospholipid/Ca++dependent protein kinase. Tamaoki, T., et al. Biochem. Biophys. Res. Commun. 135, 397, (1986)

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Somatic cell apoptosis markers and pathways in human ejaculated sperm: potential utility as indicators of sperm quality. Taylor SL, Weng SL, Fox P, et al. Mol. Hum. Reprod. 10(11), 825-34, (2004)

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Selective modulation of the glucocorticoid receptor can distinguish between transrepression of NF-κB and AP-1. De Bosscher K, Beck IM, Dejager L, et al. Cell. Mol. Life Sci. 71(1), 143-63, (2014)

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Structures of staurosporine bound to CDK2 and cAPK--new tools for structure-based design of protein kinase inhibitors. Toledo LM and Lydon NB Structure 5(12), 1551-6, (1997)

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Staurosporine a protein kinase C inhibitor interferes with proliferation of arterial smooth muscle cells. Matsumoto, H. and Sasaki, Y. Biochem. Biophys. Res. Commun. 158, 105, (1989)

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Enzymatic activity of CaMKII is not required for its interaction with the glutamate receptor subunit GluN2B. Barcomb K, Coultrap SJ, and Bayer KU Mol. Pharmacol. 84(6), 834-43, (2013)

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Two 4N cell-cycle arrests contribute to cisplatin-resistance. Shen H, Perez RE, Davaadelger B, et al. PLoS ONE 8(4), e59848, (2013)

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UCN-01 induces S and G2/M cell cycle arrest through the p53/p21(waf1) or CHK2/CDC25C pathways and can suppress invasion in human hepatoma cell lines. Wu G, Xu L, Lin N, et al. BMC Cancer 13, 167, (2013)

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Porcine JAB1 significantly enhances apoptosis induced by staurosporine. Jiang P, Wang J, Kang Z, et al. Cell Death Dis. 4, e823, (2013)

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KIT GNNK splice variants: expression in systemic mastocytosis and influence on the activating potential of the D816V mutation in mast cells. Chan EC, Bai Y, Bandara G, et al. Exp. Hematol. 41(10), 870-881.e2, (2013)

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Autotaxin is expressed in FLT3-ITD positive acute myeloid leukemia and hematopoietic stem cells and promotes cell migration and proliferation. Ortlepp C, Steudel C, Heiderich C, et al. Exp. Hematol. 41(5), 444-461.e4, (2013)

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The effect of kinase, actin, myosin and dynamin inhibitors on host cell egress by Toxoplasma gondii. Caldas LA, Seabra SH, Attias M, et al. Parasitol. Int. 62(5), 475-82, (2013)

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The role of intracellular pathways in the proliferation of human K562 cells mediated by muscarinic receptors. Aydın B, Kan B, and Cabadak H Leuk. Res. 37(9), 1144-9, (2013)

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Neuropeptide Y induces secretion of high-mobility group box 1 protein in mouse macrophage via PKC/ERK dependent pathway. Zhou JR, Zhang LD, Wei HF, et al. J. Neuroimmunol. 260(1-2), 55-9, (2013)

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Investigation into CYP3A4-mediated drug-drug interactions on midostaurin in healthy volunteers. Dutreix C, Munarini F, Lorenzo S, et al. Cancer Chemother. Pharmacol. 72(6), 1223-34, (2013)

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A chemical biology approach identifies AMPK as a modulator of melanoma oncogene MITF. Borgdorff V, Rix U, Winter GE, et al. Oncogene 33(19), 2531-9, (2014)

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Microvascular endothelial cell hyperpermeability induced by endogenous caspase 3 activator staurosporine. Sawant DA, Tharakan B, Tobin RP, et al. J. Trauma Acute Care Surg. 74(2), 516-23, (2013)

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Intracameral toxicity of bacterial components muramyl dipeptide and staurosporine: ciliary cyst formation, epithelial cell apoptosis and necrosis. Langford MP, Chen D, Gosslee J, et al. Cutan. Ocul. Toxicol. 25(2), 85-101, (2006)

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Homologous desensitization of histamine-mediated signal transduction system in C6 glioma cells. Tseng CL and Wei JW Chin. J. Physiol. 56(2), 90-100, (2013)

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[Signal transduction pathway which is involved in a protein kinase inhibitor, staurosporine, sensitivity of Saccharomyces cerevisiae]. Yoshida S Seikagaku. 67(6), 451-4, (1995)

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Amyloid β binds procaspase-9 to inhibit assembly of Apaf-1 apoptosome and intrinsic apoptosis pathway. Sharoar MG, Islam MI, Shahnawaz M, et al. Biochim. Biophys. Acta 1843(4), 685-93, (2014)

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Proteomic mapping of proteins released during necrosis and apoptosis from cultured neonatal cardiac myocytes. Marshall KD, Edwards MA, Krenz M, et al. Am. J. Physiol. Cell Physiol. 306(7), C639-47, (2014)

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Na+/H+ exchanger 1 is regulated via its lipid-interacting domain, which functions as a molecular switch: a pharmacological approach using indolocarbazole compounds. Shimada-Shimizu N, Hisamitsu T, Nakamura TY, et al. Mol. Pharmacol. 85(1), 18-28, (2014)

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Role of salt-inducible kinase 1 in the activation of MEF2-dependent transcription by BDNF. Finsterwald C, Carrard A, and Martin JL PLoS ONE 8(1), e54545, (2013)

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