Cyclin-dependent kinase 8 (CDK8) inhibitor design against cancer cell lines
Poster Number
4B
Research or Creativity Area
Pharmacy
Abstract
Cyclin-dependent kinase 8 (CDK8) is a positive regulator of the cell cycle and has been described as an oncogene in the context of chromosomal amplification in colon cancer cell lines. Knockdown of CDK8 in colon cancer cell lines led to decreased proliferation. Furthermore, transfection of NIH3T3 cells with CDK8 resulted in cellular transformation, while transfection with a kinase-dead mutant did not. CDK8 was also shown to regulate β–catenin transcriptional activity. Due to the role of many CDK family members in the regulation of the cell cycle or regulation of transcription, these proteins have become of interest as potential drug targets of cancer therapeutics.
We have discovered a CDK8 inhibitor we call Q12 and have been studying its effects in triple-negative breast cancer cell line MDA-MB-468. We also have found that Q12 may disrupt the balance between pro and anti-apoptosis proteins which result in the death of these tumor cells. Here, we describe our efforts at re-designing the Q12 molecule to optimize its ability to inhibit CDK8. We describe the synthesis, CDK8 binding and inhibition as well as its effects on MDA-MB-468 cell viability.
Location
Don and Karen DeRosa University Center (DUC) Poster Hall
Start Date
27-4-2024 10:30 AM
End Date
27-4-2024 12:30 PM
Cyclin-dependent kinase 8 (CDK8) inhibitor design against cancer cell lines
Don and Karen DeRosa University Center (DUC) Poster Hall
Cyclin-dependent kinase 8 (CDK8) is a positive regulator of the cell cycle and has been described as an oncogene in the context of chromosomal amplification in colon cancer cell lines. Knockdown of CDK8 in colon cancer cell lines led to decreased proliferation. Furthermore, transfection of NIH3T3 cells with CDK8 resulted in cellular transformation, while transfection with a kinase-dead mutant did not. CDK8 was also shown to regulate β–catenin transcriptional activity. Due to the role of many CDK family members in the regulation of the cell cycle or regulation of transcription, these proteins have become of interest as potential drug targets of cancer therapeutics.
We have discovered a CDK8 inhibitor we call Q12 and have been studying its effects in triple-negative breast cancer cell line MDA-MB-468. We also have found that Q12 may disrupt the balance between pro and anti-apoptosis proteins which result in the death of these tumor cells. Here, we describe our efforts at re-designing the Q12 molecule to optimize its ability to inhibit CDK8. We describe the synthesis, CDK8 binding and inhibition as well as its effects on MDA-MB-468 cell viability.
