Alfa Cytology is a leading customized service provider with extensive experience in basic pancreatic cancer (PC) research. We offer small molecule drug development services for pancreatic cancer to facilitate preclinical research by providing comprehensive, cutting-edge solutions to facilitate the discovery and optimization of potential therapies.
Introduction to Small Molecule Drug
Small molecule drugs are low molecular weight compounds that can easily penetrate cells, reach intracellular targets, and modulate biological processes by interacting with specific molecular targets. They inhibit key oncogenic pathways, induce apoptosis in cancer cells, and overcome resistance mechanisms, making them versatile and potent therapeutic agents in the fight against pancreatic cancer.
Fig. 1 The mechanisms of the US FDA-approved small molecule inhibitors targeting the cancers. (Liu G H, et al, 2022)
Characteristics of small molecule drugs include easy structural modification, more clinical relevance (they can be taken orally as tablets), and lower cost. In addition, these drugs have advantages over large molecule drugs such as monoclonal antibodies, peptides, and antibody-coupled drugs in terms of pharmacokinetic (PK) properties, patient compliance, cost, and drug storage and transportation.
Targets and Pipelines of Small Molecule Drugs for Pancreatic Cancer
| Targets | Therapeutics | Description | Status |
|---|---|---|---|
| KRAS | MRTX849 | MRTX849 works by irreversibly binding to the cysteine residue in the KRAS G12C mutant protein, which leads to inhibition of its oncogenic activity. |
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| JDQ443 | The drug covalently binds to this cysteine, inducing a conformational change that stabilizes KRAS in an inactive state. |
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| EGFR | Mobocertinib | By inhibiting the kinase activity of EGFR, Mobocertinib interferes with signaling pathways crucial for tumor cell proliferation and survival. |
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| DZD9008 | An oral small-molecule inhibitor, by blocking FGFR1, DZD9008 can reduce tumor growth and enhance sensitivity to other therapies. |
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| MEK | Selumetinib | By inhibiting MEK, Selumetinib disrupts the downstream phosphorylation of ERK, leading to the suppression of cell proliferation, survival, and differentiation. |
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| Binimetinib | By binding to and inhibiting MEK1/2, Binimetinib prevents the phosphorylation and activation of ERK, thereby blocking the downstream signaling that promotes tumor cell proliferation, survival, and invasion. |
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| PARP | Rucaparib | Rucaparib increases the sensitivity of pancreatic cancer cells to other DNA-damaging agents by inhibiting the accumulation of DNA damage caused by PARP. |
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| Talazoparib | Talazoparib causes double-strand breaks during DNA replication by inhibiting PARP activity. By selectively targeting these weaknesses, Talazoparib effectively reduces pancreatic cancer tumor cell viability. |
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| HDAC | Entinostat | By inhibiting HDACs, Entinostat induces hyperacetylation of histones, resulting in a more open chromatin structure and the reactivation of silenced tumor suppressor genes. |
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| Mocetinostat | Mocetinostat is a selective inhibitor of class I and IV histone deacetylases, which has been shown to enhance the immune response to tumors and increase the sensitivity of cancer cells to other therapeutic agents. |
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Our Services
With extensive research experience in the field of pancreatic cancer, Alfa Cytology offers one-stop small molecule drug development solutions for PC therapy. Our comprehensive service encompasses the entire drug development process, from initial target identification and validation to lead optimization and preclinical testing.
Alfa Cytology can pinpoint key proteins, enzymes, and signaling pathways that can be used for therapeutic intervention. Utilizing a range of cutting-edge technologies, bioinformatics tools, and expertise, we work to identify potential targets associated with the pathogenesis of pancreatic cancer to support our clients' research.
- Identification and selection of the most promising candidate compounds by combining high-throughput screening, fragment-based screening, phenotypic screening, virtual screening, computational screening, and other techniques.
- Validation of the target compounds through a series of biochemical and biophysical analyses to ensure that the identified target compounds are specific to the pancreatic cancer target.
- Hit Validation: Confirming the biological activity and specificity of hit compounds through additional assays.
- Structure-Activity Relationship (SAR) Analysis: Studying the relationship between the chemical structure of compounds and their biological activity to guide optimization efforts.
- Lead Selection: Identifying the most promising hit compounds that exhibit desirable properties such as potency, selectivity, and favorable pharmacokinetics.
The service encompasses a range of methodologies to systematically enhance the efficacy, selectivity, and safety profiles of lead compounds.
Medicinal Chemistry
Designing and synthesizing new analogs based on SAR analysis to improve potency and selectivity.
Computational Chemistry
Using molecular modeling and simulation techniques to predict the behavior of compounds and guide the design of more effective molecules.
Conducting PD assessments to understand the relationship between drug concentration and its therapeutic effect, optimizing dosing strategies.
Evaluating the pharmacokinetic profiles of lead compounds to ensure optimal dosing and bioavailability.
Conducting in vitro and in vivo assessments to identify and mitigate potential toxicities associated with lead compounds.
Small-molecule drugs can provide targeted and potent therapy options for pancreatic cancer. By partnering with Alfa Cytology, researchers and organizations have access to a wealth of expertise and resources dedicated to advancing small molecule drug development. Contact us today for more information.
Reference
- Liu G H, et al. Small molecule inhibitors targeting the cancers. MedComm. 2022, 3(4): e181.
