A randomised, double blind (sponsor unblinded), placebo-controlled, first time in human study to evaluate the safety, tolerability and pharmacokinetics of single and repeat oral doses and the food effect of GSK2556286 in healthy adult participants - CS0343-190570

Start Date25 Nov 2020

Sponsor / Collaborator

GSK Plc

NCT04472897 / RecruitingPhase 1

A Randomised, Double Blind (Sponsor Unblinded), Placebo-controlled, First Time in Human Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single and Repeat Oral Doses and the Food Effect of GSK2556286 in Healthy Adult Participants

This is a first time in human (FTIH) study to evaluate the safety, tolerability and pharmacokinetics (PK) of single and repeat ascending doses of GSK2556286 in healthy adult participants. Food effect (FE) cohorts will investigate the influence of food on the PK of GSK2556286. The study will be conducted in two parts. Part A will be a single ascending dose (SAD) including up to 11 cohorts (Cohort 1A to cohort 11A) and Part B will be a multiple ascending dose (MAD), including up to 4 cohorts (Cohort 1B to cohort 4B).

Start Date30 Oct 2020

Sponsor / Collaborator

GSK Plc

100 Clinical Results associated with Rv1625c

100 Translational Medicine associated with Rv1625c

0 Patents (Medical) associated with Rv1625c

Literatures (Medical) associated with Rv1625c

01 Jan 2017·BIO-PROTOCOL

Protein Expression Protocol for an Adenylate Cyclase Anchored by a Vibrio Quorum Sensing Receptor

Article

Author: Schultz, Joachim E ; Beltz, Stephanie

The direct regulation of a mycobacterial adenylate cyclase (Rv1625c) via exchange of its membrane anchor by the quorum sensing receptor CqsS (Vibrio harveyi) has recently been reported ( Beltz et al., 2016 ). This protocol describes the expression and membrane preparation for these chimeric proteins.

01 Mar 2006·Journal of Molecular BiologyQ2 · BIOLOGY

A Structural Basis for the Role of Nucleotide Specifying Residues in Regulating the Oligomerization of the Rv1625c Adenylyl Cyclase from M.tuberculosis

Q2 · BIOLOGY

Article

Author: Avinash R. Shenoy ; Sandhya S. Visweswariah ; Amit D. Ketkar ; Kaza Suguna ; Udupi A. Ramagopal

The Rv1625c Class III adenylyl cyclase from Mycobacterium tuberculosis is a homodimeric enzyme with two catalytic centers at the dimer interface, and shows sequence similarity with the mammalian adenylyl and guanylyl cyclases. Mutation of the substrate-specifying residues in the catalytic domain of Rv1625c, either independently or together, to those present in guanylyl cyclases not only failed to confer guanylyl cyclase activity to the protein, but also severely abrogated the adenylyl cyclase activity of the enzyme. Biochemical analysis revealed alterations in the behavior of the mutants on ion-exchange chromatography, indicating differences in the surface-exposed charge upon mutation of substrate-specifying residues. The mutant proteins showed alterations in oligomeric status as compared to the wild-type enzyme, and differing abilities to heterodimerize with the wild-type protein. The crystal structure of a mutant has been solved to a resolution of 2.7A. On the basis of the structure, and additional biochemical studies, we provide possible reasons for the altered properties of the mutant proteins, as well as highlight unique structural features of the Rv1625c adenylyl cyclase.

15 Apr 2005·Biochemical JournalQ3 · BIOLOGY

Characterization of phylogenetically distant members of the adenylate cyclase family from mycobacteria: Rv1647 fromMycobacterium tuberculosisand its orthologue ML1399 fromM. leprae

Q3 · BIOLOGY

Article

Author: MAHALINGAM, Mohana ; SREENATH, Nandini P. ; SHENOY, Avinash R. ; VISWESWARIAH, Sandhya S.

Analysis of the genome sequence of Mycobacterium tuberculosis H37Rv has identified 16 genes that are similar to the mammalian adenylate and guanylate cyclases. Rv1647 was predicted to be an active adenylate cyclase but its position in a phylogenetically distant branch from the other enzymes characterized so far from M. tuberculosis makes it an interestingly divergent nucleotide cyclase to study. In agreement with its divergence at the sequence level from other nucleotide cyclases, the cloning, expression and purification of Rv1647 revealed differences in its biochemical properties from the previously characterized Rv1625c adenylate cyclase. Adenylate cyclase activity of Rv1647 was activated by detergents but was resistant to high concentrations of salt. Mutations of substrate-specifying residues to those present in guanylate cyclases failed to convert the enzyme into a guanylate cyclase, and did not alter its oligomeric status. Orthologues of Rv1647 could be found in M. leprae, M. avium and M. smegmatis. The orthologue from M. leprae (ML1399) was cloned, and the protein was expressed, purified and shown biochemically to be an adenylate cyclase, thus representing the first adenylate cyclase to be described from M. leprae. Importantly, Western-blot analysis of subcellular fractions from M. tuberculosis and M. leprae revealed that the Rv1647 and ML1399 gene products respectively were expressed in these bacteria. Additionally, M. tuberculosis was also found to express the Rv1625c adenylate cyclase, suggesting that multiple adenylate cyclase proteins may be expressed simultaneously in this organism. These results suggest that class III cyclase-like gene products probably have an important role to play in the physiology and perhaps the pathology of these medically important bacteria.

Analysis

Perform a panoramic analysis of this field.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

Rv1625c

Basic Info

Related

Analysis