Isotope Science / Alfa Chemistry

Stable Isotope-Labeled Antitumor Drugs: A Powerful Tool for Cancer Research

About Stable Isotope-Labeled Antitumor Drug

Stable isotope-labeled (SIL) antitumor drugs are those drugs whose constituents have been reconstituted into a single or multiple stable isotopes (e.g., deuterium, carbon-13, nitrogen-15). Such isotopes don't alter the bioactivity of the drug, but they are simpler to detect and measure using mass spectrometry (MS). That's why the drug and its metabolites can be much more accurately and sensitively identified and quantified in biological samples.
Finding good antitumor treatments is a major task in today's medicine. SIL compounds are now essential ingredients in the discovery, development and clinical research of antitumor drugs. These drugs, based on a stable isotope or several, have many benefits over old unlabeled drugs. Alfa Chemistry is pleased to present our new series of SIL antitumor compounds to help with cancer research and better treatment development.

Advantages of SIL Antitumor Drugs

  • Improved Sensitivity and Specificity: SIL drugs enhance analytical techniques sensitivity and specificity to allow quantification of drug concentrations in biological specimens even at low concentrations.
  • More Complete Pharmacokinetic and Pharmacodynamic Research: SIL drugs enable in-depth ADME (absorption, distribution, metabolism, and excretion) and drug efficacy and toxicity studies.
  • Mechanism of Action: The effects of antitumor drugs can be investigated in molecular scale by using SIL compounds such as protein-drug interactions and metabolic routes.
  • Clinical Use: SIL medicines can be leveraged to tailor medicine protocols, track drug response and resistance, and tailor treatment programs.

Alfa Chemistry's SIL Antitumor Drug Portfolio

ProductsTargeted TherapiesType
LapatinibHER2-positive metastatic breast cancer.Kinase Inhibitors
NilotinibChronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL).Kinase Inhibitors
BaricitinibRheumatoid arthritis and alopecia areata.Kinase Inhibitors
TucatinibHER2-positive metastatic breast cancer.Kinase Inhibitors
PonatinibChronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL).Kinase Inhibitors
AlectinibAnaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC).Kinase Inhibitors
CrizotinibALK-positive NSCLC and ROS1 fusion-positive NSCLC.Kinase Inhibitors
FlumatinibChronic myelogenous leukemia (CML).Kinase Inhibitors
RuxolitinibMyelofibrosis and polycythemia vera.Kinase Inhibitors
LenvatinibThyroid cancer, renal cell carcinoma, and hepatocellular carcinoma.Kinase Inhibitors
DasatinibCML and Ph+ ALL.Kinase Inhibitors
ApatinibGastrointestinal stromal tumors (GIST).Kinase Inhibitors
DacomitinibNon-small cell lung cancer (NSCLC).Kinase Inhibitors
GefitinibNSCLC with EGFR mutations.Kinase Inhibitors
ImatinibCML, gastrointestinal stromal tumors (GIST), and other cancers.Kinase Inhibitors
N-desmethylimatinibA metabolite of imatinib with similar activity.Kinase Inhibitors
IbrutinibChronic lymphocytic leukemia (CLL) and mantle cell lymphoma.Kinase Inhibitors
OsimertinibNSCLC with EGFR mutations, including T790M mutation.Kinase Inhibitors
AfatinibNSCLC with EGFR mutations.Kinase Inhibitors
ErlotinibNSCLC with EGFR mutations.Kinase Inhibitors
DoxorubicinA broad-spectrum anticancer drug used to treat various cancers.Traditional Chemotherapy Agents
MethotrexateAn antifolate drug used to treat various cancers, autoimmune diseases, and ectopic pregnancies.Traditional Chemotherapy Agents
PaclitaxelA taxane chemotherapy drug used to treat various cancers, including breast, lung, and ovarian cancer.Traditional Chemotherapy Agents
DocetaxelA variety of cancers - including breast, head and neck, gastric, prostate, and non-small cell lung cancer.Traditional Chemotherapy Agents
5-FluorouracilA pyrimidine analog chemotherapy drug used to treat various cancers, including colorectal, breast, and gastrointestinal cancers.Traditional Chemotherapy Agents

Application Examples of SIL Antitumor Drugs

SIL antitumor drug monitoring system

The work of Evelina Cardoso, et al. used HPLC paired with tandem MS/MS to simultaneously analyze human plasma for six anticancer protein kinase inhibitors (PKIs) with their SILs as Internal Standards (IS): dabrafenib-D9, trametinib-13C6, vemurafenib-13C6, cobimetinib-13C6, pazopanib-13C D3, regorafenib-13C D3. [1]

SIL antitumor drugs for drug release study

Fig 1. Stable isotope docetaxel-d5 release.Stable isotope drug release method. [2]

A ultrafiltration was used to quantify nanodrug release from biological mediums and to measure both encapsulated and unencapsulated nanodrugs in plasma and the nanodrug release. The approach uses stable isotopes of the drug to explain formulation-induced variation in protein binding and equilibrium binding of the drug to formulation ingredients. Specifically, it was determined whether a stable isotope-labeled docetaxel-d5 (DTX-d5) tracer behaved equivalently to normal isotope docetaxel (DTX) with respect to protein binding in plasma. [2]

References

  • Cardoso E, et al. Journal of chromatography B, 2018, 1083, 124-136.
  • Skoczen S, et al. Journal of Controlled Release, 2015, 220: 169-174.
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