cdk inhibitor sns-032  (Sunesis Inc)

Journal: International Journal of Molecular Sciences

Article Title: Antitumoral Activity of a CDK9 PROTAC Compound in HER2-Positive Breast Cancer

doi: 10.3390/ijms23105476

Figure Lengend Snippet: Evaluation of CDK9 protein expression and antiproliferative activity of SNS-032 and THAL-SNS-032 in breast cancer cell lines. Protein levels of CDK9 in all cell lines were analyzed by Western blot ( A ). Band quantification of CDK9 protein level referred to GAPDH as the loading control ( B ). THAL-SNS-032 EC50 obtained by MTT proliferation assays in breast cancer cell lines after 72 h of treatment ( C ). Heat map depicting the effect of different doses of THAL-SNS-032 in cell death in a breast cancer cell line panel ( D ). THAL-SNS-032 reduced cell viability more than SNS-032 in BT474, BT474-RH, BT474-TDM1R, and BT474-LAPA-R at the doses indicated (72 h). We used MTT assay ( E ). * p < 0.05; ** p < 0.01; *** p < 0.001.

Article Snippet: The CDK-inhibitor SNS-032 was purchased from MedChemExpress (Monmouth Junction, NJ, USA) and the CDK-PROTAC THAL-SNS-032 was purchased from Tocris Bioscience (Bio-Techne R&D Systems, S.LU, Minneapolis, MN, USA).

Techniques: Expressing, Activity Assay, Western Blot, Control, MTT Assay

Journal: International Journal of Molecular Sciences

Article Title: Antitumoral Activity of a CDK9 PROTAC Compound in HER2-Positive Breast Cancer

doi: 10.3390/ijms23105476

Figure Lengend Snippet: Antitumoral effect of SNS-032 and THAL-SNS-032 in 3D-matrix and adhesion assays in breast cancer lines and CDKs protein level evaluation after treatments. SNS-032 or THAL-SNS-032 (100 nM) was applied for 72 h to BT474, RH, and TDM1R cells seeded in a Matrigel matrix. Results presented refer to control cells. Scale bar = 100 μm ( A ). Cell adhesion to fibronectin substrate after 24 h of exposure to SNS-032 or THAL-SNS-032 (100 nM) ( B ). Expression levels of CDK9, CDK7, CDK1, and CDK2 in BT474, RH, and TDM1R cells treated with SNS-032 and THAL-SNS-032 at the times indicated at 50 nM. Scale bar = 100 μm ( C ). * p < 0.05; ** p < 0.01; *** p < 0.001.

Article Snippet: The CDK-inhibitor SNS-032 was purchased from MedChemExpress (Monmouth Junction, NJ, USA) and the CDK-PROTAC THAL-SNS-032 was purchased from Tocris Bioscience (Bio-Techne R&D Systems, S.LU, Minneapolis, MN, USA).

Techniques: Control, Expressing

Journal: International Journal of Molecular Sciences

Article Title: Antitumoral Activity of a CDK9 PROTAC Compound in HER2-Positive Breast Cancer

doi: 10.3390/ijms23105476

Figure Lengend Snippet: Cell cycle analyses of SNS-032 and THAL-SNS-032 in BT474 and BT474-derived cell lines representative of adaptive resistance. Bar graph showing populations generated by flow cytometry in each phase of cell cycle for BT474, RH, and TDM1R cells of SNS-032 (50 nM) and THAL-SNS-032 (50 nM) for 24 h ( A ). Expression of proteins involved in cell cycle in cell lines treated with SNS-032 (50 nM) and THAL-SNS-032 (50 nM) for 24 h. GAPDH was used as a loading control ( B ). * p < 0.05.

Article Snippet: The CDK-inhibitor SNS-032 was purchased from MedChemExpress (Monmouth Junction, NJ, USA) and the CDK-PROTAC THAL-SNS-032 was purchased from Tocris Bioscience (Bio-Techne R&D Systems, S.LU, Minneapolis, MN, USA).

Techniques: Derivative Assay, Generated, Flow Cytometry, Expressing, Control

Journal: International Journal of Molecular Sciences

Article Title: Antitumoral Activity of a CDK9 PROTAC Compound in HER2-Positive Breast Cancer

doi: 10.3390/ijms23105476

Figure Lengend Snippet: Apoptosis process of SNS-032 and THAL-SNS-032 in BT474 and BT474-derived cell lines representative of adaptive resistance. Cell death following SNS-032 (50 nM) or THAL-SNS-032 (50 nM) treatment after 72 h in BT474 and BT474-derived cell lines representative of adaptive resistance cell lines and resistant cell lines was evaluated by flow cytometry with annexin V and propidium iodide staining ( A ). Expression of proteins involved in cell death was evaluated by Western blot in cells lines treated at 50 nM (SNS-032 and THAL-SNS-032) for 72 h. GAPDH was used as a loading control ( B ). * p < 0.05; ** p < 0.01; *** p < 0.001.

Article Snippet: The CDK-inhibitor SNS-032 was purchased from MedChemExpress (Monmouth Junction, NJ, USA) and the CDK-PROTAC THAL-SNS-032 was purchased from Tocris Bioscience (Bio-Techne R&D Systems, S.LU, Minneapolis, MN, USA).

Techniques: Derivative Assay, Flow Cytometry, Staining, Expressing, Western Blot, Control

Journal: International Journal of Molecular Sciences

Article Title: Antitumoral Activity of a CDK9 PROTAC Compound in HER2-Positive Breast Cancer

doi: 10.3390/ijms23105476

Figure Lengend Snippet: THAL-SNS-032 therapeutic index exploration. Normal breast cancer cell line MCF10A was treated with 25, 50, and 100 nM of SNS-032 and THAL-SNS-032. Proliferation was evaluated by MTT assay after 72 h of treatment ( A ). Table summary of THAL-SNS-032 doses, frequency, and route of administration in in vivo studies ( B ). Mice engrafted with BT474 cells were treated with THAL-SNS-032 (at indicated doses, I.P.) and controls with excipient. Mean of tumor volume ± SEM at each point was represented. Day of dose administration and sacrifice are indicated in each graph ( C ). Mice weight during the in vivo experiments. Treated mice (specially 10 mg/kg and 5 mg/kg) lost weight after THAL-SNS-032 administration ( D ). Western blot showing the expression levels of CDKs in tumors treated or untreated with THAL-SNS-032 ( E ). Heat map of the dependency score obtained by DepMap to evaluate CDKs dependency after CRISPR (DepMap 21Q3 Public + Score, CERES) or RNAi (Achilles + DRIVE + Marcotte, DEMETER2) inhibition ( F ). Body map showing expression of CDK9, CDK7, CDK1, and CDK2 in normal tissues in Log2(Transcript Per Million + 1) Scale. Adapted from: GEPIA2 web server (Gene Expression Profiling Interactive Analysis. http://gepia2.cancer-pku.cn/ , accessed on 27 May 2021) ( G ). *** p < 0.001.

Article Snippet: The CDK-inhibitor SNS-032 was purchased from MedChemExpress (Monmouth Junction, NJ, USA) and the CDK-PROTAC THAL-SNS-032 was purchased from Tocris Bioscience (Bio-Techne R&D Systems, S.LU, Minneapolis, MN, USA).

Techniques: MTT Assay, In Vivo, Western Blot, Expressing, CRISPR, Inhibition, Gene Expression

Journal: Oncotarget

Article Title: ERpS294 is a biomarker of ligand or mutational ERα activation and a breast cancer target for CDK2 inhibition

doi: 10.18632/oncotarget.12735

Figure Lengend Snippet: CDK inhibitors and their target specificities, evaluated in this study

Article Snippet: CDK inhibitors including SNS (SNS-032), JNJ (JNJ7706621), DIA (Dinaciclib, SCH727965), PD (Palbociclib, PD0332991) and BMS (BMS-265246) were commercially obtained from Selleckchem, except for CYC065 which was kindly provided by Cyclacel (Dundee, UK).

Techniques: