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The inhibitor EC-70124, is currently undergoing advanced preclinical development by EntreChem SL. EC-70124 is a hybrid natural product obtained from genetically modified bacteria by combinatorial biosynthesis.

EntreChem SL is a Spanish spin off from the University of Oviedo, and its shareholders include original co-founders and local family offices. Private financing is complemented by public funds from MINECO, Genome Spain Foundation (now FECYT), FICYT, IDEPA, SRP and the 7FP and H2020 from the European Union.

More information:

Dr. Alberto Ocaña: albertoo@sescam.jccm.es
+34 967 597 100, ext. 37087

Dr. Atanasio Pandiella: atanasio@usal.es
+34 923 294 815

Dr. Francisco Morís: fmv@entrechem.com
+34 985 259 021

and also:

ESMO 2014 meeting:
www.webges.com/cslide/library/esmo/browse/
search/e4d#9faD037R


CHUA:
www.chospab.es/investigacion/oncologia_traslacional/intro.htm

CIC:
www.cicancer.org

EntreChem SL:
www.entrechem.com
EntreChem presents in ESMO 2014 congress:
Activity of the multi-targeted kinase inhibitor EC-70124 in colorectal cancer

September 26th, 2014 - Oviedo (Spain)

•  Colorectal cancer (CRC) shows alterations on the activation status of receptor tyrosine kinases (RTKs) and intracellular cytoplasmic kinases, some of which correlate between primary tumors and liver metastases.

EC-70124, a kinase inhibitor being developed at EntreChem SL, shows strong antiproliferative effect on CRC by acting on relevant activated targets observed in human samples, including SRC and pS6. It causes G2/M arrest and induces DNA damage. EC-70124 also synergizes with chemotherapies used in the clinic.


The results of a collaborative research from EntreChem SL (Oviedo) and the Translational Cancer Research Unit at Albacete University Hospital, CHUA (Albacete, Spain) focused on searching new strategies for Colorectal Cancer, globally the third most common type of cancer making up about 10% of all worldwide cases, has been presented in a poster at the European Society For Medical Oncology congress (ESMO 2014) held on Sep 26th - 30th 2014 in Madrid (Spain).

The research, directed by Dr. Alberto Ocaña, Director of the Translational Cancer Research Unit, Albacete University Hospital, and participation from Dr. Atanasio Pandiella from the Translation Oncopharmacology Unit at CIC (Salamanca, Spain) focuses on activation status of receptor tyrosine kinases and intracellular cytoplasmic kinases, especially members of the ErbB receptors, the VEGFR family and FGFR, and phosphorylation of signalling regulators, including components of the PI3K/mTOR/AKT pathway, STAT1 and Alk. Notably, there is a correlation in the expression of some activated kinases between primary tumors and liver metastases.

EC-70124 is active against a panel of CRC cells in the submicromolar range, and induces a similar effect as dasatinib (a Src kinase inhibitor), on the inhibition of cell migration in SW620 and HT29 cell lines. EC-70124 inhibited relevant pathways in CRC including the PI3K/mTOR pathway (shown by pS6 and pAkt inhibition) as well as pSrc. In addition, EC-70124 showed strong arrest at the G2/M phase at 24h and induction of apoptosis at 48h (confirmed by Annexin and PARP degradation). Additionally, EC-70124 induces DNA damage, observed by the accumulation of pH2Ax and pChk2. Studies in combination with standard of care showed synergy with chemotherapeutic agents through induction of apoptosis raising the possibility to explore these combinations in the clinical setting.



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