The two main studies it was in patients it performed worse than the SOC and then a Phase III which apparently did as good as SOC but I can’t seem to find the study data on that.Here it is.
Randomized Trial of Doxorubicin, Bisantrene, and Mitoxantrone in Advanced Breast Cancer.pdfThe historic clinical data is great because it gives a clear indication that the drug works very well even though researchers didn't understand the drug.
Since then, AML therapies are leaps ahead and even on the solid tumour front anthracyclines have gone a way to reduce cardio toxicity…So bisantrene would really need to knock it out of the park, and how long in the clinic will that take to prove against SOC and which patient population? Have they even got a trial in the works?!Do you understand what a new drug class means? FTO is implicated in chemoresistance across 25 different drug classes and >30 cancer types, which means Bisantrenes strength is in combination with therapies to improve efficacy of treatment. If you consider the cardioprotective MoA, then you have a cardiosynergy drug which has never been seen before. The Sheba 2 update demonstrated 40% ORR and no cardiotoxicity despite 2 cardiotoxic drugs used in combination that patients were refractory to. First in class drugs capture the largest market share.
Given bisantrene seems to insert itself into the patients DNA there is no data on the long term adverse neural and immune outcomes. If there is potential negative effects would patients prefer a therapy that could alter their DNA or not?Here is partitioning data from the 1980s demonstrating that Bisantrene doesn't cross the blood-brain barrier, so long-term adverse neural outcomes are not a worry. The IC50 values for inhibition of topoisomerase II is 18,000 nM, while inhibition of FTO is 143.2 nM - this means Bisantrene selects FTO 126x more potently than topo II thus intercalation of DNA. The established IC50 values for biological targets ordered from lowest to highest being FTO inhibition 143.2 nM, cardio MoA (unknown) [I estimate 2,000 nM], telomerase inhibition 3,600 nM, and topoisomerase inhibition 18,000 nM. Patients included into the P3 breast cancer received upwards of 7,000 nM of Bisantrene which was well tolerated.
You do realise the drug was approved in France and given to children, some of which are alive today with families of their own..
Disposition and Metabolic Profile of a New Antitumor Agent Bisantrene.pdf
Regarding immune outcomes, Bisantrene has almost the greatest influences on DEG for M2 activation of any approved or unapproved drug. M2 macrophages are associated with anti-inflammatory responses and tissue repair/remodelling.
FTO inhibition is the other angle but there are more selective compounds (FB23-2 & CS1) that have shown very strong FTO inhibition with less ‘off target’ effects. You're also completely wrong re CS2 and FB23-2, which require 5x and 18x more drug to achieve the same inhibition of FTO as Bisantrene. More drug into humans equals more likelihood chance of off-target effects.
I tried to warn you not to discuss RAC or Bisantrene. You don't know what you are talking about, and you haven't done your homework.
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