RE:RE:RE:RE:RE:FDA Clears Peptide-Drug Conjugate for RRMMAgain, isotope or chemo drug, the principle is the same. Apeptide with affinity to an overexpressed receptor is able to bind with it while carrying a cytotoxic agent. The only difference, the chemo drug needs to be released free inside the cancer cell, so the linker needs to be seltively cleavable inside the cell. In the other case, it was not that. The drug is part of the peptide, a dipeptide, two amino acids linked together. Two AA is the minimum to be called a peptide, and there is no linker involved, the link between the two AA is the peptide bond. You have this kind of bond between every AA in a peptide. In TH1902 a 17 AA peptide, there is 16 peptide bonds all cleavable by proteases.
scarlet1967 wrote: My point is as the other drug was an amino acid as per yourself rather than a peptide therefore it wouldn't classify as a PDC but a radiopeptide would classify?!
jfm1330 wrote: Sorry, you are wrong on that. Lutathera is a real PDC with a real peptide, a real linker and a real cytotoxic agent. The only difference is the fact that the linker is not cleavable since the isotope does not need to be free to emit radiations.
scarlet1967 wrote: We can say the same for Lutathera as the drug is a radiopeptide. Lutathera’s MOA is also a bit different than TH19... series, Lutathera cancer therapy is really a PRRT (Peptide Receptor Radionuclide Therapy) a radioactive targeted therapy.
“Lutathera is a radiolabeled somatostatin analog (a cell-targeting protein called octreotide combined with a radionuclide called Lutetium)."
Lutetium is a chemical element from periodic table.
jfm1330 wrote: To call this drug a PDC is a strech in my opinion. The drug itself, melphalan is like an unnatural amino acid and it is linked through a peptide bond to another unnatural amino acid para-fluoro phenyalanine. So the peptide is the smallest peptide possible, a di peptide (2 AA) and there is no linker, only a peptide bond. As a reminder, peptides are polymer of amino acids linked together through peptide bonds. These bonds are recongnized by enzymes and cleaved. The in vitro half life of this drug is very short, only 10 minutes. So again, to call it a PDC does not reflect the reality in my opinion. One thing is sure, we are not talking here about a PDC in the full sense of the expression. In my view, Lutathera is still the only real PDC approved.
scarlet1967 wrote: FDA yesterday approved first PDC for relapsed/refractory multiple myeloma which is great news for company’s TH19.. series, this is a milestone for PDC in any cancer therapeutic program.
Good recognition for the technology.
"The FDA Friday approved the first anticancer peptide-drug conjugate, melphalan flufenamide, or melflufen, for use in combination with dexamethasone in adult patients with relapsed/refractory multiple myeloma (RRMM), who have received at least 4 prior lines of therapy and whose disease is refractory to at least 1 proteasome inhibitor, 1 immunomodulatory agent, and 1 CD38-directed monoclonal antibody."
https://www.ajmc.com/view/fda-clears-peptide-drug-conjugate-for-rrmm