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Target Discovery & Validation in Pancreatic Cancer

Target Discovery & Validation in Pancreatic Cancer

Pancreatic cancer (PC) is a common gastrointestinal tumor with unmet needs. The disease is characterized by multi-gene, multi-step complex evolution from onset to spread. Moreover, PC has an insidious occurrence and very poor prognosis, and it is difficult to obtain clinical specimens at different stages and to observe the tumorigenesis and progression in patients with PC. In order to move beyond the current dire situation of the current lack of PC treatment options, identifying the best protocols and new treatment options is a challenge that must be faced. Alfa Cytology is an integrated research, development, and manufacturing organization providing scientific services, primarily ranging from early discovery and development to preclinical research. Here, we provide target discovery & validation services for PC small molecule drug development.

Small molecule inhibitors of PC

As understanding of the biology and molecular characteristics of PC continues to expand, the development of drugs that target a variety of specific tumor signaling pathways has been recognized as a promising approach to improving treatment options for patients with PC. In the last decade, more and more small molecule inhibitors of PC have been discovered and developed. To date, there are a large number of small molecules under investigation. And at least 10 small molecules targeting PC are in clinical trials, such as the dual inhibitor of focal adhesion kinase and pyruvate kinase 2 (PF-562271 7), inhibitors of protein phosphatase 2A (LB-100 8), and focal adhesion kinase (C4 9). As potential PC treatment agents, they have shown encouraging antitumor activity and promising safety and tolerability in early clinical studies.

Chemical structures of small molecule inhibitors of protein kinases under investigation for their efficacy against pancreatic cancerFig.1 Chemical structures of small molecule inhibitors of protein kinases under investigation for their efficacy against pancreatic cancer: PD173074 (42), PKC412 (43), BGB324 (44), GSK2256098 (45), PF573228 (46), binimetinib (47) and cobimetinib (48). (Sun, Jufeng, et al.,2020)

The service offering at Alfa Cytology

The selection of research targets is an important part of drug discovery. Our goal is to help researchers discover new, effective small molecule drug targets for the treatment of PC. We have an in-depth understanding of PC cell and receptor biology, its inherent molecular heterogeneity, and in particular, the complex molecular pathology of PC improved by genomic analysis. With a range of platforms and expertise in PC research and therapeutic areas, we are able to deliver many new small molecule drug targets to our customers.

  • Cancer genome sequencing

Whole-genome sequencing (WGS) using next-generation sequencing (NGS) provides base-pair level analysis of mutations specific to cancer tissue. WGS greatly facilitates the discovery of new cancer-associated variants, including single nucleotide locus variants (SNV), copy number variations, insertions/deletions (indel), and structural variants. Using genome-wide unbiased cancer genome sequencing, a more systematic method, we can identify some important and frequently mutated oncogenes.

  • Genome-wide RNA interference (RNAi)

This approach is used to understand how cancer genes interact in dynamic networks, helping to prioritize certain target loci that may be particularly important in PC.

  • High content imaging platform and in vitro ELISA screening method

Based on these screening tools, we can help our customers analyze how the compound interacts with a target at the subcellular level, optimizing your hit identification strategies.

  • In vitro and in vivo target validation platform

Several popular PC models are available at our company, including PC cell models, PC organoids, genetically engineered mouse models, and transplantation models. These models serve as useful tools for drug target validation.

Our services support these popular biological targets for PC therapy

Our services support these popular biological targets for PC therapy
  • Protein kinases and tyrosine kinases
  • Signal transducer and activator of transcription3 (STAT3)
  • Focal adhesion kinase (FAK)
  • Mitogen-activated protein kinase
  • Bcl-2 family proteins (Bcl-2, Bcl-xL, Bcl-w, and Mcl-1)
  • Histone deacetylases (HDACs)

If you are interested in our services, please contact us for more details. You can get in touch with our staff directly and receive professional, reliable, and fast feedback.

References

  1. Hoelder, Swen, Paul A. Clarke, and Paul Workman. "Discovery of small molecule cancer drugs: successes, challenges and opportunities." Molecular oncology 6.2 (2012): 155-176.
  2. Sun, Jufeng, et al. "Small molecule inhibitors in pancreatic cancer." RSC medicinal chemistry 11.2 (2020): 164-183.
All of our services are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.