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Bix02189

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BIX02189 is a small molecule inhibitor that acts as a selective and potent inhibitor of dual specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A). It is used as a research tool to study the biological functions of DYRK1A.

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Lab products found in correlation

Xmd8 92, by Bio-Techne (2 mentions) Bafilomycin a1, by Merck Group (1 mentions) M154cf500, by Thermo Fisher Scientific (1 mentions) S0015, by Thermo Fisher Scientific (1 mentions) Bay 11 7085, by Bio-Techne (1 mentions) Pd98059, by Bio-Techne (1 mentions) Taqman universal pcr master mix, by Thermo Fisher Scientific (1 mentions) 7900ht fast real time pcr system, by Thermo Fisher Scientific (1 mentions) 4d nucleofector, by Lonza (1 mentions) Panobinostat lbh589, by Selleck Chemicals (1 mentions) Hdaci, by Selleck Chemicals (1 mentions) Trametinib gsk1120212, by Selleck Chemicals (1 mentions) Adavosertib mk 1775, by Selleck Chemicals (1 mentions) Wee1i, by Selleck Chemicals (1 mentions) Sotorasib amg 510, by MedChemExpress (1 mentions) Afatinib, by LC Laboratories (1 mentions) Midostaurin pkc412, by LC Laboratories (1 mentions) Alisertib, by Selleck Chemicals (1 mentions) Trametinib, by Selleck Chemicals (1 mentions) Sb203850, by Merck Group (1 mentions)

6 protocols using bix02189

1

Inhibiting Autophagy and MEK Signaling

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Unless otherwise stated, cells were treated with 10 µM BIX02189 (Tocris 4842) and 10 µM XMD8–92 (Tocris 4132) for 16 h and with 50 nM Bafilomycin A1 (Sigma B1793) for 2 h.
Craig J.E., Miller J.N., Rayavarapu R.R., Hong Z., Bulut G.B., Zhuang W., Sakurada S.M., Temirov J., Low J.A., Chen T., Pruett-Miller S.M., Huang L.J, & Potts M.B. (2020). MEKK3-MEK5-ERK5 signaling promotes mitochondrial degradation. Cell Death Discovery, 6, 107.
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2

Keratinocyte Culture and Inhibitor Assays

Cited 1 time
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Normal human keratinocytes (NHKs) were established from healthy adults as previously described(60 (link)) and grown in medium 154 CF (Thermofisher M154CF500) with human keratinocyte growth supplement (Thermofisher S0015). Inhibitors used included the MEK1/2 inhibitor PD98059 (Tocris 1213), the MEK5 inhibitor Bix02189 (Tocris 4842) and the IκBα phosphorylation inhibitor Bay 11–7085 (Tocris 1743) according to the manufecturer’s specifications. siRNA was introduced by electroporation using Lonza 4D-nucleofector following manufacturer’s instructions. Cytokine stimulations were performed as previously reported(61 (link)). qRT-PCR was performed on a 7900HT Fast Real-time PCR system (Applied Biosystems) with TaqMan Universal PCR Master Mix (ThermoFisher 4304437).
Liang Y., Xing X., Beamer M.A., Swindell W.R., Sarkar M.K., Roberts L.W., Voorhees J.J., Kahlenberg J.M., Harms P.W., Johnston A, & Gudjonsson J.E. (2016). STEAPs comprise a novel inflammatory nexus in pustular skin disorders. The Journal of allergy and clinical immunology, 139(4), 1217-1227.
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3

Pharmacological Inhibition of Oncogenic Signaling

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Pharmacological inhibitors to MEK1/2 (Trametinib/GSK1120212, MEKi), HDAC (Panobinostat/LBH589, HDACi) and WEE1 (Adavosertib/MK-1775, WEE1i) were acquired from Selleckchem; to MEK5-K2 (BIX02189, MEK5i) was purchased from Tocris. Lestaurtinib/L6307 (mtPKCi), Neratinib (pan-HERi) and Afatinib (EGFRi) were obtained from LC Laboratories, and Midostaurin/PKC412 (mtPKCi), Sotorasib/AMG-510 (KRASi), Darovasertib (PKCAi), Barasertib (AURKBi), Adagrasib/MRTX849 (KRASi) and MG132 (proteasome inhibitor) were purchased from MedChemExpress. Dabrafenib (RAFi) was a kind gift from Imanol Arozarena (Navarrabiomed, Spain).
Macaya I., Roman M., Welch C., Entrialgo-Cadierno R., Salmon M., Santos A., Feliu I., Kovalski J., Lopez I., Rodriguez-Remirez M., Palomino-Echeverria S., Lonfgren S.M., Ferrero M., Calabuig S., Ludwig I.A., Lara-Astiaso D., Jantus-Lewintre E., Guruceaga E., Narayanan S., Ponz-Sarvise M., Pineda-Lucena A., Lecanda F., Ruggero D., Khatri P., Santamaria E., Fernandez-Irigoyen J., Ferrer I., Paz-Ares L., Drosten M., Barbacid M., Gil-Bazo I, & Vicent S. (2023). Signature-driven repurposing of Midostaurin for combination with MEK1/2 and KRASG12C inhibitors in lung cancer. Nature Communications, 14, 6332.
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4

Functional Genomics Screening of FOSL1, AURKA, TACC3

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shRNAs to FOSL1: sh1–TRCN0000019541, sh2–TRCN0000019543, sh3–TRCN0000019539. FOSL1 sh1 was also cloned into a TET inducible version of pLKO.1 vector52 (link). shRNAs to Fosl1: sh1-TRCN0000042683, sh2-TRCN0000042686. shRNAs to AURKA: sh1–TRCN0000000656, sh2–TRCN0000000657. shRNAs to TACC3: sh1–TRCN0000290485, sh2–TRCN0000308273. Control shRNA to green fluorescence protein (GFP) has been previously described15 (link). pDONR223-AURKA was a gift from William Hahn & David Root (Addgene plasmid # 23532). Pharmacological inhibitors: U0126, SP600125, LY294002 and SB203850 were from Sigma; BIX02189 was from Tocris; trametinib and alisertib were from Selleckchem.
Vallejo A., Perurena N., Guruceaga E., Mazur P.K., Martinez-Canarias S., Zandueta C., Valencia K., Arricibita A., Gwinn D., Sayles L.C., Chuang C.H., Guembe L., Bailey P., Chang D.K., Biankin A., Ponz-Sarvise M., Andersen J.B., Khatri P., Bozec A., Sweet-Cordero E.A., Sage J., Lecanda F, & Vicent S. (2017). An integrative approach unveils FOSL1 as an oncogene vulnerability in KRAS-driven lung and pancreatic cancer. Nature Communications, 8, 14294.
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5

Macrophage Inhibitors Pretreatment Protocol

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In some experiments, macrophages were pretreated with the following inhibitors: BIX 02189 (Tocris), a selective inhibitor of MEK5; XMD 8-92 (Tocris), an inhibitor of ERK5; and 10058-F4 (Tocris), a c-Myc-Max dimerization inhibitor.
Optimal doses of inhibitors were determined for each experiment. Mock pretreatment was performed with vehicle alone (DMSO) at a maximum concentration of 0.05%.
Luiz J.P.M., Toller-Kawahisa J.E., Viacava P.R., Nascimento D.C., Pereira P.T., Saraiva A.L., Prado D.S., LeBert M., Giurisato E., Tournier C., Cunha T.M., Cunha F.Q., Quesniaux V., Ryffel B, & Alves-Filho J.C. (2020). MEK5/ERK5 signaling mediates IL-4-induced M2 macrophage differentiation through regulation of c-Myc expression. Journal of leukocyte biology, 108(4).
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6

Recombinant Growth Factor Acquisition

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Recombinant human vascular endothelial growth factor (VEGF)-A165 was purchased from R&D Systems Inc. (Abingdon, UK). Recombinant human epidermal growth factor (EGF) was purchased from Peprotech (London, UK). BIX02189, AX15836 and BIRB796 were purchased from Tocris Bioscience (Bristol, UK), and JWG071 was purchased from Sigma (Poole, UK).
Mondru A.K., Aljasir M.A., Alrumayh A., Nithianandarajah G.N., Ahmed K., Muller J., Goldring C.E., Wilm B, & Cross M.J. (2023). VEGF Stimulates Activation of ERK5 in the Absence of C-Terminal Phosphorylation Preventing Nuclear Localization and Facilitating AKT Activation in Endothelial Cells. Cells, 12(6), 967.
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