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The CDK9 (cyclin-dependent kinase 9) gene encodes two subtypes of protein, the major 42 kDa protein and the minor 55 kDa protein. CDK9 plays a key role in controlling global (non-ribosomal) transcription, especially including gene expression regulated by super-enhancers, and a large number of DNA regulatory elements ("enhancers") that drive cell identity-related gene transcription, including MYC and apoptosis regulator MCL-1. MYC is involved in cells growth and cell cycle progression downstream proto-oncogenes. CDK9 also appears to be involved in several physiological processes of extra-transcribed cells, including differentiation, apoptosis, and signal transduction.
Figure 1: Regulation of transcription by CDK9. (Muhammed H Rahaman. 2016)
Functional details of CDK9
Target CDK9 therapy
Given that CDK9 is a kinase, it is considered to be a relatively easy target for drug discovery and provides a pathway for indirect targeting of MCL-1 and MYC, while MCL-1 and MYC are considered to be more current challenging targets in drug discovery.
Table1. List of CDK9 inhibitors that reached preclinical or clinical development. (Muhammed H Rahaman. 2016)
|Dinaciclib||Multiple clinical trials for hematologic and solid tumors|
|Flavopiridol||Phase II clinical study against different solid tumors and leukemia (the only CDK9 inhibitor in clinical trial in prostate cancer)|
|P276-00||Phase I/II clinical trials for pancreatic cancer, multiple myeloma, mantle cell myeloma, breast cancer and melanoma|
|Roscovitine||Phase I for advanced solid tumors, Phase II studies for Cushing's disease and cystic fibrosis|
|SNS-032||Phase I clinical trials in advanced solid tumors and advanced B-lymphoid malignancies|
|TG02||Phase 1 clinical trials in advanced hematological malignancies|
CDK9 Gene Editing Service
CRISPR/Cas9 PlatformCB provides comprehensive CRISPR/Cas9 gene editing services and products to a wide range of genomics researchers. Based on our platform, we can help you effectively regulate your target genes editing in vivo and in vitro using the CRISPR/Cas9 system.
Mutation via CRISPR Gene Editing
We are able to perform specific DNA deletions, mutations or substitutions to study gene function with CRISPR/Cas9 gene editing technology with high precision. Available services:
➢ Point Mutation
➢ Conditional knockout/knock-in
➢ Floxed allele insertion
Mark by CRISPR gene editing
Using the CRISPR/Cas9 gene editing technology, CRISPR/Cas9 PlatformCB is able to tag your genes at the endogenous locus and visualize them with fluorescent proteins or immune-tags for biochemical studies. Available services:
➢ Fluorescent tag
➢ Custom tags and combinations are also available
CRISPR/Cas9 PlatformCB has more than a decade of experience in integrating CRISPR/Cas9 technology into more than 200 different cell lines, including those that are easy to transfect and those that are difficult to transfect. We also successfully implemented the CRISPR/Cas9 gene-edited in animal models, which has been well recognized by customers.
|Blood Lineage Cells||RAW264.7, HMC1.2, K562, U937 etc.|
|Cancer Cell Lines||HEK293, HEK293T, Hela, MCF7, Neuro2a, HepG2, U87, etc.|
|Other Cell Lines||NIH3T3, MCF10, HEME, SW10 etc.|
|Animal models we offered||mouse, rat, rabbit, zebrafish, C. elegans, etc.|
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