To address the need for improved Pol I inhibitors with minimal off-target effects we collaborated with Pimera Inc to develop a selective 2nd-generation Pol I inhibitor, PMR-116. We show that combinatorial therapy with CX-5461 and both Flavopiridol and Dinaciclib have a synergistic effect in vitro and significantly increase the survival of acute myeloid leukaemia (AML) models in vivo. Our data indicates that inhibition of both Pol I (by CX-5461) and Pol II (by CDK9 inhibitors) can be used in as a therapy to extend survival and reduce acquired resistance.
almost 2 years ago
BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)
PMR-116 treatment decreased tumour volume in all PDX tested including complete response in a line in which tumour volume decreased by ~90% compared to baseline.We believe this new RNA Pol I inhibitor shows promising results in a wide range of preclinical models and may exert higher efficacy in tumours expressing high levels of MYC. PMR-116 is currently in Phase I dose escalation trial in patient with solid tumours (ACTRN12620001146987).
almost 3 years ago
Preclinical
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PTEN (Phosphatase and tensin homolog) • EIF4EBP1 (Eukaryotic translation initiation factor 4E binding protein 1)