A First-in-human, Randomized, Participant and Investigator Blinded, Placebo Controlled, Single and Multiple Ascending Dose Study to Assess the Safety, Tolerability and Pharmacokinetics of EDI048 in Healthy Volunteers

A first-in-human study to evaluate the safety, tolerability, and pharmacokinetics of single ascending doses and multiple ascending doses of EDI048 administered orally in healthy volunteers.

Start Date29 Apr 2022

Sponsor / Collaborator

Novartis Pharmaceuticals Corp.

ISRCTN38693215 / RecruitingPhase 1

A first-in-human, randomized, participant and investigator blinded, placebo controlled, single and multiple ascending dose study to assess the safety, tolerability and pharmacokinetics of EDI048 in healthy volunteers

Start Date25 Apr 2022

Sponsor / Collaborator

Novartis Pharma AG

100 Clinical Results associated with CpPI(4)K

100 Translational Medicine associated with CpPI(4)K

0 Patents (Medical) associated with CpPI(4)K

Literatures (Medical) associated with CpPI(4)K

01 Sep 2016·Journal of General VirologyQ3 · MEDICINE

Foot-and-mouth disease virus genome replication is unaffected by inhibition of type III phosphatidylinositol-4-kinases

Q3 · MEDICINE

Article

Author: Loundras, Eleni-Anna ; Stonehouse, Nicola J. ; Herod, Morgan R. ; Harris, Mark

Foot-and-mouth disease virus (FMDV) causes economically damaging infections of cloven-hooved animals, with outbreaks resulting in large financial losses to the agricultural industry. Due to the highly contagious nature of FMDV, research with infectious virus is restricted to a limited number of key facilities worldwide. FMDV sub-genomic replicons are therefore important tools for the study of viral translation and genome replication. The type III phosphatidylinositol-4-kinases (PI4Ks) are a family of enzymes that plays a key role in the production of replication complexes (viral factories) of a number of positive-sense RNA viruses and represents a potential target for novel pan-viral therapeutics. Here, we investigated whether type III PI4Ks also play a role in the FMDV life cycle, using a combination of FMDV sub-genomic replicons and bicistronic internal ribosome entry site (IRES)-containing reporter plasmids. We demonstrated that replication of the FMDV replicon was unaffected by inhibitors of either PI4KIIIα or PI4KIIIβ. However, PIK93, an inhibitor previously demonstrated to target PI4KIIIβ, did inhibit IRES-mediated protein translation. Consistent with this, cells transfected with FMDV replicons did not exhibit elevated levels of phosphatidylinositol-4-phosphate lipids. These results are therefore supportive of the hypothesis that FMDV genome replication does not require type III PI4K activity and does not activate these kinases.

01 Jan 2016·Methods in Molecular Biology

Identification of the Interactome of a Palmitoylated Membrane Protein, Phosphatidylinositol 4-Kinase Type II Alpha

Article

Author: Gokhale, Avanti ; Ryder, Pearl V ; Zlatic, Stephanie A ; Faundez, Victor

Phosphatidylinositol 4-kinases (PI4K) are enzymes responsible for the production of phosphatidylinositol 4-phosphates, important intermediates in several cell signaling pathways. PI4KIIα is the most abundant membrane-associated kinase in mammalian cells and is involved in a variety of essential cellular functions. However, the precise role(s) of PI4KIIα in the cell is not yet completely deciphered. Here we present an experimental protocol that uses a chemical cross-linker, DSP, combined with immunoprecipitation and immunoaffinity purification to identify novel PI4KIIα interactors. As predicted, PI4KIIα participates in transient, low-affinity interactions that are stabilized by the use of DSP. Using this optimized protocol we have successfully identified actin cytoskeleton regulators-the WASH complex and RhoGEF1, as major novel interactors of PI4KIIα. While this chapter focuses on the PI4KIIα interactome, this protocol can and has been used to generate other membrane interactome networks.

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