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AACR 2017 | Poster 4182/5 – The two novel BTK-inhibitors M2951 and M7583 show in vivo anti-tumor activity in pre-clinical models of ABC type Diffuse Large B-Cell Lymphoma
At the American Association for Cancer Research (AACR) annual meeting in Washington, DC, USA, on Tuesday 4th April, a poster session titled “Targeting Protein Kinases and DNA Repair” took place.
One of the posters on display (4182 / 5) was titled “The two novel BTK-inhibitors M2951 and M7583 show in vivo anti-tumor activity in pre-clinical models of B cell lymphoma” by Eugenio Gaudio from the Institute of Oncology Research, Bellinzona, Switzerland, and colleagues.
This group aimed to evaluated the anti-tumor activity of M2951 and M7583 (two novel, highly selective, irreversible BTK inhibitors) in an in vivo ABC DLBCL model. Xenografts were established by SC injection of TMD8 cells (100µL of PBS, 107 cells/mouse) into the left flanks of female NOD-SCID mice. Treatments (QD, po) began with an average tumor volume of 100mm3 on groups of 10 mice each.
Key Highlights:
- Mice were treated with three different concentrations of M7583 (1, 3, or 10mg/Kg) or M2951 (5, 15, or 25mg/Kg) or vehicle (control group)
- M2951 slowed tumor growth at all doses starting after 10 days of treatment
- M7583 at 3 and 10mg/Kg showed stronger anti-tumor activity than M2951, apparent after 5 days of treatment (P < 0.05) and improving with time (after 10 days, P < 0.005)
- Most groups had to be stopped after 2 weeks of treatment (D30 after engraftment) due to reaching maximum tumor volume; however, mice treated with M7583 at the two highest doses were able to continue treatment for additional six (3mg/Kg) or ten days (10mg/Kg) when tumors became bigger than 2,000mm3, indicating a high activity of M7583
- No body weight losses or signs of toxicity were observed
The poster concluded that M2951 and M7583 displayed encouraging anti-tumor activity in vivo in their ABC DLBCL murine model. The data supports further investigation of these compounds for the treatment of B-cell Lymphomas.
References
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