The business replaces a traditionally-run laundry; if it succeeds it will be a potent proof-of-concept for the cooperative movement.
Direct observation of slower tRNA diffusion than reloading and translation would be the most potent proof for this hypothesis.
It is now feasible to identify reasonably potent and selective small molecules that provide chemical proof-of-concept in vivo directly from high throughput screening.
Demonstrating proof-of-principle, studies of olaparib, a potent oral PARP inhibitor, have demonstrated monotherapy activity and acceptable toxicity in patients with ovarian or breast cancer who have a germline BRCA1 or BRCA2 mutation [ 12, 13].
Modification of both azithromycin and erythromycin A resulted in promising reductions in the invasion inhibitory IC50 to levels nearing those achieved clinically for the parent compounds, providing a proof-of-concept for the potential development of potent invasion inhibitors.
These results provide proof-of-principle that more chronic administration of a potent, orally delivered JAK2 inhibitor should have therapeutic effects on the polycythemia, and perhaps the myelofibrosis and hemostatic abnormalities, suffered by MPD patients carrying the JAK2 V617F mutation.
For now, a formal proof-of-concept must await the generation of more potent MCL-1 inhibitors with improved drug-like properties.
The manufacturing of EPO analogues with no hematopoietic but potent neuroprotective properties, e.g. CEPO (carbamoylated EPO) [ 12], delivered proof-of-principle that brain effects of EPO are not necessarily mediated by its hematopoietic actions.
More recently, we provided a strong scientific rationale for progressing the potent pan-PI3 kinase/mTOR inhibitor Omipalisib (GSK2126458) as a novel anti-fibrotic agent in a proof-of-mechanism trial in IPF (https://clinicaltrials.gov/ct2/show/NCT01725139 22.gov/ct2/show/NCT01725139 22
Our laboratory provided the first proof-of-concept that double-stranded short interfering RNA (ds-siRNA) can act as potent and specific antiviral agents.
These studies represent a preclinical proof-of-concept that demonstrate that, in advanced mouse models, a mutanome-targeting vaccine can elicit potent immunogenicity and confer tumour growth inhibition and control.
