Internal standard Product for ADC New Drug Development
Antibody-drug conjugates (ADCs) are targeted drugs composed of antibodies, linkers and cytotoxic molecules. Unlike chemotherapy, ADCs target and kill tumor cells without harming healthy cells, by integrating the antigen specificity of monoclonal antibodies (mAbs) with antibody fragments. The ADC cytotoxin (also known as the payload) is the most important component, as it determines the potency of the ADCs to kill cancer cells. It is the "bullet" responsible for destroying cancer cells[1].
Figure 1 ADC drug
Isotope-labeled cytotoxin (such as MMAE-d8, Exatecan-d5 mesylate) have become the gold standard for quantitative detection due to the no matrix effects and high sensitivity in LCMS. This can provide important data support for their pharmacokinetics, biodistribution and facilitate the development of ADC new drugs[2].
- [1] Nat Rev Drug Discov. 2021 Aug;20(8):583-584.
- [2] J Labelled Comp Radiopharm. 2014 May 15;57(5):350-7.
- 1
- 2
- Formula: C25H21D5FN3O7S
- Molecular Weight: 536.58
Exatecan-d5 (DX8951f-d5) mesylate is deuterium labeled Exatecan mesylate (HY-13631A). Exatecan mesylate is a DNA topoisomerase I inhibitor, with an IC50 of 2.2 μM (0.975 μg/mL). Exatecan mesylate can be used in cancer research.
- Formula: C39H59D8N5O7
- Molecular Weight: 726.03
MMAE-d8 is a deuterated labeled MMAE, a potent mitotic inhibitor and a tubulin inhibitor.
- Formula: C26H19D5FN3O6
- Molecular Weight: 498.51
DXd-d5 is a deuterium labeled DXd. DXd is a potent DNA topoisomerase I inhibitor, with an IC50 of 0.31 μM, used as a conjugated drug of HER2-targeting ADC (DS-8201a) .
- Formula: C22H17D3N2O5
- Molecular Weight: 395.42
SN-38-d3 is the deuterium labeled SN-38. SN-38 (NK012) is an active metabolite of the Topoisomerase I inhibitor Irinotecan. SN-38 (NK012) inhibits DNA and RNA synthesis with IC50s of 0.077 and 1.3 μM, respectively.
- Formula: C41H60D3NO14S
- Molecular Weight: 829.02
Eribulin-d3 (mesylate) is a deuterium labeled Eribulin mesylate. Eribulin mesylate is a microtubule targeting agent that is used for the research of cancer.
- Formula: C47H46D5NO14
- Molecular Weight: 858.94
Paclitaxel-d5 is a deuterium-labeled Paclitaxel. Paclitaxel is a naturally occurring antineoplastic agent and stabilizes tubulin polymerization.
- Formula: C20H19D3N8O5
- Molecular Weight: 457.46
Methotrexate-d3 is the deuterated-labeled Methotrexate (HY-14519). Methotrexate (Amethopterin; CL14377; WR19039) is an orally active antifolate (Antifolate). Methotrexate inhibits dihydrofolate reductase (DHFR), blocks tetrahydrofolate production, suppresses purine/pyrimidine synthesis and transmethylation, and causes intracellular accumulation of AICAR. Methotrexate promotes extracellular adenosine release, regulates the cytokine network, and inhibits the alarmin function of HMGB1. Methotrexate induces apoptosis and cytotoxicity, upregulates the expression of iNOS and COX-2, suppresses hippocampal neurogenesis, and induces pulmonary fibrosis. Methotrexate is used in the research of various immune and inflammation-related diseases such as arthritis, psoriasis, systemic lupus erythematosus, as well as pulmonary fibrosis and breast cancer.
- Formula: C22H13D5N2O7
- Molecular Weight: 427.42
7-Hydroxymethyl-10,11-MDCPT-d5 is deuterium labeled 7-Hydroxymethyl-10,11-MDCPT, which is a is a payload that can be used for ADC synthesis.
- Formula: C68H97D8N11O15
- Molecular Weight: 1324.68
VcMMAE-d8 is an isotope of VcMMAE (HY-15575). VcMMAE-d8 is a agent-linker conjugate for ADC with potent antitumor activity by using the anti-mitotic agent, monomethyl auristatin E (MMAE, a tubulin inhibitor), linked via the lysosomally cleavable dipeptide, valine-citrulline (vc).
- Formula: C39H54D8N6O6S
- Molecular Weight: 751.06
PF-06380101-d8 (Aur0101-d8) is a deuterium labeled PF-06380101 (HY-12522). PF-06380101, an Auristatin microtubule inhibitor, is a cytotoxic Dolastatin 10 analogue.
- Formula: C39H58D8ClN5O8
- Molecular Weight: 776.47
MMAF-d8 (hydrochloride)e is a deuterated form of MMAF hydrochloride, which is a microtubule disrupting agent.
- Formula: C52H51D5FN9O13
- Molecular Weight: 1039.08
Deruxtecan-d5 is deuterium labeled Deruxtecan (HY-13631E). Deruxtecan is an ADC drug-linker conjugate composed of an DX-8951 derivative (DXd) and a maleimide-GGFG peptide linker, used for synthesizing DS-8201 and U3-1402.
- Formula: C52H54D2FN9O13
- Molecular Weight: 1036.06
Deruxtecan-d2 is the deuterium labeled Deruxtecan (HY-13631E). Deruxtecan is an ADC drug-linker conjugate composed of an DX-8951 derivative (DXd) and a maleimide-GGFG peptide linker, used for synthesizing DS-8201 and U3-1402.
- Formula: C2113C18H70N7O17P3S
- Molecular Weight: 1051.86
Stearoyl coenzyme A-13C18 (lithium) is the 13C labeled Stearoyl coenzyme A lithium. Stearoyl coenzyme A (Stearoyl-CoA) lithium is an active compound that can be used as a substrate for the determination of stearoyl-Coenzyme desaturase in microsomes.
- Formula: C47H46D5NO14
- Molecular Weight: 858.94
Paclitaxel-d5 (benzoyloxy) is the deuterium labeled Paclitaxel. Paclitaxel is a naturally occurring antineoplastic agent and stabilizes tubulin polymerization. Paclitaxel can cause both mitotic arrest and apoptotic cell death. Paclitaxel also induces autophagy.
- Formula: C20H11D5N2O4
- Molecular Weight: 353.38
Camptothecin-d5 is the deuterium labeled Camptothecin. Camptothecin (CPT), a kind of alkaloid, is a DNA topoisomerase I (Topo I) inhibitor with an IC50 of 679 nM. Camptothecin (CPT) exhibits powerful antineoplastic activity against colorectal, breast, lung and ovarian cancers, modulates hypoxia-inducible factor-1α (HIF-1α) activity by changing microRNAs (miRNA) expression patterns in human cancer cells.
- Formula: C27H21D5FN3O6
- Molecular Weight: 512.54
Deruxtecan 2-hydroxypropanamide-d5 is a deuterated isotope of Deruxtecan 2-hydroxypropanamide (HY-153891) .
- Formula: C25H23D3FN3O7S
- Molecular Weight: 534.57
Exatecan-d3 (DX8951f-d3) mesylate is deuterium-labeled Exatecan mesylate (HY-13631A). Exatecan mesylate is a DNA topoisomerase I inhibitor, with an IC50 of 0.975 μg/mL.
- Formula: C28H31D5N6O10
- Molecular Weight: 621.65
MC-Gly-Gly-Phe-Gly-NH-CH2-O-CH2COOH-d5 is deuterated labeled MC-Gly-Gly-Phe-Gly-NH-CH2-O-CH2COOH.
- 1
- 2
