1428536-05-3Relevant academic research and scientific papers
Antibody drug conjugates (ADCs) charged with HDAC inhibitor for targeted epigenetic modulation
Cini, Elena,Faltoni, Valentina,Petricci, Elena,Taddei, Maurizio,Salvini, Laura,Giannini, Giuseppe,Vesci, Loredana,Milazzo, Ferdinando Maria,Anastasi, Anna Maria,Battistuzzi, Gianfranco,De Santis, Rita
, p. 6490 - 6496 (2018)
We describe here two novel antibody-drug conjugates loaded with the HDAC inhibitor ST7612AA1 (IC50 equal to 0.07 μM on NCI-H460 cells), a thiol-based molecule with a moderate toxicity in vivo. Two payloads were prepared using cleavable and non-cleavable linkers. After anchoring to cetuximab through amide bond with lysines, the resulting HDAC inhibitor-antibody conjugates showed ability to recognize EGFR and efficient internalization in tumor cells. Both ADCs induced sensible increment of histones 3 and 4 and alpha-tubulin acetylation. Animal models of human solid tumors showed high anti-tumor efficacy of the conjugates without the toxicity generally observed with traditional ADCs delivering highly potent cytotoxic drugs. These compounds, the first ADCs charged with not highly cytotoxic warheads, are potentially suitable for epigenetic modulation, extending the ADC strategy to the targeted delivery of HDAC inhibitors with many possible therapeutic applications beyond cancer.
ST7612AA1, a thioacetate-ω(γ-lactam carboxamide) derivative selected from a novel generation of oral HDAC inhibitors
Barbarino, Marcella,Battistuzzi, Gianfranco,Cabri, Walter,Fant, Nicola,Giannini, Giuseppe,Guglielmi, Mario Berardino,Milazzo, Ferdinando M.,Mor, Marco,Pala, Daniele,Pisano, Claudio,Rivara, Silvia,Santaniello, Mos,Taddei, Maurizio,Vesci, Loredana,Vignola, Davide
, p. 8358 - 8377 (2014/12/11)
A systematic study of medicinal chemistry aimed at identifying a new generation of HDAC inhibitors, through the introduction of a thiol zinc-binding group (ZBG) and of an amide-lactam in the ω-position of the polyethylene chain of the vorinostat scaffold,
NEW THIO DERIVATIVES BEARING LACTAMS AS POTENT HDAC INHIBITORS AND THEIR USES AS MEDICAMENTS
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Paragraph 0211; 0212; 0213; 0214; 0215; 0216; 0253-0256, (2014/07/23)
The present invention relates to novel amide compounds of Formula (I), and their use as anti-tumoral and pro-apoptotic agents. The invention includes the use of such compounds in medicine, in relation to cancer disease as well as other diseases where an i
NEW THIO DERIVATIVES BEARING LACTAMS AS POTENT HDAC INHIBITORS AND THEIR USES AS MEDICAMENTS
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Page/Page column 28; 31, (2013/04/10)
The present invention relates to novel amide compounds of Formula (I), and their use as anti-tumoral and pro-apoptotic agents. The invention includes the use of such compounds in medicine, in relation to cancer disease as well as other diseases where an i
