Gdc 0879

Manufactured by Selleck Chemicals

Sourced in United States

GDC-0879 is a chemical compound used in laboratory research. It is a selective inhibitor of the kinase enzyme CDK4/6. The core function of GDC-0879 is to inhibit the activity of the CDK4/6 enzyme complex.

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Lab products found in correlation

8 protocols using gdc 0879

Compound Preparation for Cancer Research

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Vemurafenib was kindly provided by Plexxikon. Trametinib, dabrafenib, GDC-0879, sorafenib, and Cdk4 Inhibitor II (NSC 625987) were purchased from Selleck Chemicals. All compounds were dissolved in DMSO, aliquoted, and stored at −20°C until used.

Mologni L., Costanza M., Sharma G.G., Viltadi M., Massimino L., Citterio S., Purgante S., Raman H., Pirola A., Zucchetti M., Piazza R, & Gambacorti-Passerini C. (2018). Concomitant BCORL1 and BRAF Mutations in Vemurafenib-Resistant Melanoma Cells. Neoplasia (New York, N.Y.), 20(5), 467-477.

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Comparative Analysis of BRAF and MEK Inhibitors

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BRAFi used are as follows: PLX4032 (vemurafenib; MedChemExpress, #HY-12057), LGX818 (encorafenib; MedChemExpress, #HY-15605), GSK2118436A (dabrafenib; Selleckchem, #S2807), PLX8394 (MedChemExpress, #HY-18972), AZ628 (Selleckchem, #S2746), GDC0879 (Selleckchem, #S1104), LY3009120 (Selleckchem, #S7842), and TAK632 (Selleckchem, #S7291). MEKi used are as follows: AZD6244 (selumetinib; Selleckchem, #S1008), BAY86-9766 (refametinib; MedChemExpress, #HY-102156), and benzyl-coelenterazine (NanoLight, #301).

Röck R., Mayrhofer J.E., Torres-Quesada O., Enzler F., Raffeiner A., Raffeiner P., Feichtner A., Huber R.G., Koide S., Taylor S.S., Troppmair J, & Stefan E. (2019). BRAF inhibitors promote intermediate BRAF(V600E) conformations and binary interactions with activated RAS. Science Advances, 5(8), eaav8463.

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Protein Expression Analysis of Signaling Pathways

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Whole cell lysates were prepared in lysis buffer (20 mM Tris-HCl, pH 7.5, 150 mM NaCl, 1 mM EDTA, 1% NP40 and 10% Glycerol), resolved by SDS-PAGE and blotted with indicated antibodies. The following antibodies were used in this study: Anti-β-catenin, anti-FAK, anti-phospho-FAK (Tyr397), anti-ERK1/2, anti-SRC and anti-Integrin β1 (Cell Signaling Technology, Danvers, MA); anti-GSK3α/β, anti-phospho-GSK3α/β (Tyr279/216), anti-phospho-ERK1/2, anti-β-Actin and anti-SP1 (Santa Cruz Biotechnology, Dallas, TX). SuperSignal West Pico Chemiluminescent Substrate and SuperSignal Western Blot Enhancer (Thermo Fisher Scientific, Waltham, MA) were used to enhance western signal when needed. Vemurafenib, Dabrafenib, GDC-0879 (8 (link)), Erlotinib, SCH772984 (9 (link)), LY3009120 (10 (link)) and ICG-001(11 (link)) were purchased from Selleck Chemicals (Houston, TX). PF-562271 (12 (link)) was purchased from MedKoo Biosciences (Chapel Hill, NC). PLX7904 (13 (link)) was obtained from Plexxikon (Berkeley, CA). Gelucire is a gift from Gattefosse (Paramus, NJ). NE-PER Nuclear and Cytoplasmic Extraction Reagents from Thermo Fisher Scientific were used for subcellular fractionation according to manufacturer’s protocol.

Chen G., Gao C., Gao X., Zhang D.H., Kuan S.F., Burns T.F, & Hu J. (2017). Wnt/β-catenin pathway activation mediates adaptive resistance to BRAF inhibition in colorectal cancer. Molecular cancer therapeutics, 17(4), 806-813.

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Screening of Protein Kinase Inhibitors for TNBC

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The fifty-five protein kinase inhibitors (PKIs) were purchased from following sources: BML-275, FR 180204, IKK16, GW 843682X, NSC 109555, NU7441, PD407824, PF 573228, SB 218078, TCS PIM-1-1, TCS PIM-1-4a, and TPCA-1 from Tocris Biosciences (Bristol, UK); indirubin-3′-monoxime and Ro-31-8220 from Calbiochem (San Diego, CA, USA); A-769662, bosutinib, chelerythrine, CP690550, fasudil, gefitinib, imatinib, nilotinib, PKC412, roscovitine, SNS-314, and tozasertib from LC Laboratories (Woburn, MA, USA); AT7867, AT9283, AZD1152, AZD1480, BI 2536, BIX 02189, CHIR-99021, CI-1040, CYC116, danusertib, enzastaurin, GDC-0879, INCB018424, JNJ-7706621, KU-55933, LY2228820, MLN8237, PD-0325901, PF-4708671, PLX-4032, PLX-4720, SB216763, SNS-032, SP600125, VX-702, Y-27632, and ZM447439 from Selleck Chemicals (Houston, TX, USA); U0126 from Promega (Madison, WI, USA); TBCA from Millipore (Burlington, MA, USA).
All TNBC cells in this study were obtained from the American Type Culture Collection (Manassas, VA, USA). The cultured cells were monitor by trypan blue cell counting as described previously [58 (link)].

Yi Y.W., You K.S., Han S., Ha I.J., Park J.S., Lee S.G, & Seong Y.S. (2022). Inhibition of IκB Kinase Is a Potential Therapeutic Strategy to Circumvent Resistance to Epidermal Growth Factor Receptor Inhibition in Triple-Negative Breast Cancer Cells. Cancers, 14(21), 5215.

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Therapeutic Compounds for Cancer Research

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Dabrafenib, AZ628, regorafenib, PLX4720, vemurafenib, sorafenib, GDC-0879, SB590885 and SU11248 were purchased from Selleck (Houston, TX, USA). zVAD.fmk was obtained from Abcam (Cambridge, UK), necrostatin-1 was from Tocris (Bristol, UK) and acetaminophen was from Sigma-Aldrich (St. Louis, MO, USA). Smac mimetic was synthesized and purified as previously described.^{30 (link)}

Li J.X., Feng J.M., Wang Y., Li X.H., Chen X.X., Su Y., Shen Y.Y., Chen Y., Xiong B., Yang C.H., Ding J, & Miao Z.H. (2014). The B-RafV600E inhibitor dabrafenib selectively inhibits RIP3 and alleviates acetaminophen-induced liver injury. Cell Death & Disease, 5(6), e1278-.

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Investigating MAPK Signaling in DCs

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To investigate the role of MAPK signaling in DCs of human and murine origin, inhibitors blocking components of the MAPK signaling were added to the cultures. LY3009120 (1 µM, Cat. No. S7842, Selleckchem), GDC-0879 (1 µM, Cat. No. S1104 Selleckchem), Raf265 (0.5 µM, Cat. No. S2161 Selleckchem), and Kobe005 (10 µM, Cat. No. S8303 Selleckchem) were employed to block RAF Kinases. Trametinib (1 µM, Cat. No. S2673 Selleckchem) was employed to block MEK1/2. In order to block proteasomal degradation, MG132 (10 µM, Merck Millipore) was added to the cultures for 6 h. All inhibitors were dissolved in DMSO unless otherwise stated, DCs were treated with the inhibitors in the presence or absence of LPS stimulation (100 ng/ml, Cat. No. L6143, Sigma) for 48 h and used for further analyses. Alternatively, DCs were stimulated with Pam3CSK4 (1 µg/ml, Cat. No. tlrl-pms, InvivoGen), Poly(I:C) (50 µg/ml, Cat. No. 27–4732–01, GE Healthcare) or with a combination of LPS and PGE₂ (1 µg/ml, Cat. No. 14010, Cayman, solved in X-VIVO-15/10% ethanol).

Riegel K., Schlöder J., Sobczak M., Jonuleit H., Thiede B., Schild H, & Rajalingam K. (2019). RAF kinases are stabilized and required for dendritic cell differentiation and function. Cell Death and Differentiation, 27(4), 1300-1315.

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Comprehensive Signaling Pathway Analysis

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Antibodies used in this study were anti-B-RAF (D9T6S), anti-GFP, anti-HSP90, anti-p44/42 MAPK (ERK1/2), anti-phospho-p44/22 (ERK1/2) (Thr 202 /Tyr 204 ), anti-MEK1/2, anti-phospho-MEK1/2 (Ser 217/212 ), anti-AKT, anti-phospho-AKT (S473), anti-EGFR (D38B1), anti-phospho-EGFR (Tyr 1068 ) (D7A5) (all from Cell Signaling Technology), anti-RAF-B (F-7), anti-α-tubulin (Santa Cruz Biotechnology), anti-glyceraldehyde-3-phosphate dehydrogenase (Abcam), and anti-HA (3F10) (Roche Diagnostics). Belvarafenib (HM95573), dabrafenib, encorafenib, GDC-0879, lifirafenib (BGB-283), LY3009120, MLN2480, naporafenib (LXH254), sorafenib, TAK-632, trametinib, vemurafenib, and XL888 were purchased from SelleckChem. All inhibitors were dissolved in dimethyl sulfoxide (DMSO).

Lauinger M., Christen D., Klar R.F.U., Roubaty C., Heilig C.E., Stumpe M., Knox J.J., Radulovich N., Tamblyn L., Xie I.Y., Horak P., Forschner A., Bitzer M., Wittel U.A., Boerries M., Ball C.R., Heining C., Glimm H., Fröhlich M., Hübschmann D., Gallinger S., Fritsch R., Fröhling S., O'Kane G.M., Dengjel J, & Brummer T. (2023). BRAF^Δβ3-αC in-frame deletion mutants differ in their dimerization propensity, HSP90 dependence, and druggability. Science advances, 9(35).

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Kinase Inhibitor Assay Protocol

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Radioactive ATP γ-P32 (# NEG002Z250UC) was purchased from Perkin Elmer. Vemurafenib, Dabrafenib, PB-PLX7904, TAK-632, AZ-628, GDC-0879, SB-590885 were purchased from Selleckchem. Inhibitors were dissolved in DMSO to produce 10 mM stocks and stored at −20°C. Non-hydrolyzable GTP analog GppNHp (G0635) was purchased from Sigma. Alkaline Phosphatase, Calf Intestinal (CIP) (M0290) was purchased from NEB. Gel filtration standard (#151–1901) was purchased from Bio-Rad. All other reagents were purchased without further purification.

Cope N., Candelora C., Wong K., Kumar S., Nan H., Grasso M., Novak B., Li Y., Marmorstein R, & Wang Z. (2018). Mechanism of BRAF Activation Through Biochemical Characterization of the Recombinant Full-Length Protein. Chembiochem : a European journal of chemical biology, 19(18), 1988-1997.

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