Last update 19 Sep 2024

ROBO2

Last update 19 Sep 2024

Basic Info

Synonyms

KIAA1568, ROBO2, roundabout guidance receptor 2

+ [1]

Introduction

Receptor for SLIT2, and probably SLIT1, which are thought to act as molecular guidance cue in cellular migration, including axonal navigation at the ventral midline of the neural tube and projection of axons to different regions during neuronal development.

Drugs associated with ROBO2

PF-06730512

Target

ROBO2 x SLIT2

Mechanism

ROBO2 antagonists [+2]

Active Org.

Boston University School of Medicine [+2]

Originator Org.

Pfizer Inc.

Active Indication

Glomerulosclerosis, Focal Segmental

Inactive Indication-

Drug Highest PhasePhase 2

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with ROBO2

NCT03448692 / TerminatedPhase 2

A PHASE 2, 24-WEEK, ADAPTIVE, OPEN LABEL, SEQUENTIAL COHORT TRIAL TO EVALUATE THE EFFICACY, SAFETY, TOLERABILITY AND PHARMACOKINETICS OF PF-06730512 FOLLOWING MULTIPLE DOSES IN ADULT SUBJECTS WITH FOCAL SEGMENTAL GLOMERULOSCLEROSIS (FSGS)

The purpose of this Phase 2 adaptive study is to evaluate the efficacy, safety, tolerability and pharmacokinetics of PF-06730512 following multiple intravenous infusions in adult subjects with FSGS.

Start Date15 Oct 2018

Sponsor / Collaborator

Pfizer Inc.

NCT03146065 / CompletedPhase 1

A Phase 1, Randomized, Double Blind, Sponsor-open, Placebo-controlled, First-in-human Trial To Evaluate The Safety, Tolerability, And Pharmacokinetics Of Pf-06730512 After Single And Multiple Ascending Intravenous Infusion Or Subcutaneous Administration To Healthy Adult Subjects And An Open-label Evaluation In Healthy Japanese Subjects

The purpose of this study is to determine the safety, tolerability and pharmacokinetics of escalating single and multiple intravenous (IV) infusions and subcutaneous (SC) injections of PF-06730512 in healthy subjects.

Start Date10 May 2017

Sponsor / Collaborator

Pfizer Inc.

100 Clinical Results associated with ROBO2

100 Translational Medicine associated with ROBO2

0 Patents (Medical) associated with ROBO2

351

Literatures (Medical) associated with ROBO2

01 Jun 2024·Pesticide Biochemistry and Physiology

Genetic architecture of the toxicological response to eucalyptol and citronellal in Drosophila melanogaster

Article

Author: Alzogaray, Raul ; Sabio, Mariana C ; Fanara, Juan J

The excessive and indiscriminate use of synthetic insecticides has led to environmental pollution, wildlife destruction, and adverse effects on human health, while simultaneously giving rise to resistance in insect pest populations. This adaptive trait is expressed through various mechanisms, such as changes in the cuticle, heightened activities of detoxifying enzymes, and alterations in the sites of action that reduce their affinity for insecticides. In this context, we associate variation in toxicological response with genomic variation, to identify genetic polymorphisms underlying the different steps of the insect (genotype)-response (phenotype)-insecticide (environment) interaction. Under this framework, our objective was to investigate the genetic factors involved in the toxicological response of D. melanogaster lines when exposed to citronellal and eucalyptol vapors (monoterpenes of plant origin). We quantified KT50 in adult males, representing the time necessary for half of the exposed individuals to be turned upside down (unable to walk or fly). Since the genomes of all lines used are completely sequenced, we perform a Genome Wide Association Study to analyze the genetic underpinnings of the toxicological response. Our investigation enabled the identification of 656 genetic polymorphisms and 316 candidate genes responsible for the overall phenotypic variation. Among these, 162 candidate genes (77.1%) exhibited specificity to citronellal, 45 (21.4%) were specific to eucalyptol, and 3 candidate genes (1.5%) namely CG34345, robo2, and Ac13E, were implicated in the variation for both monoterpenes. These suggest a widespread adaptability in the response to insecticides, encompassing genes influenced by monoterpenes and those orchestrating resistance to the toxicity of these compounds.

03 Mar 2024·Nucleosides, Nucleotides & Nucleic Acids

SALL4 advances the proliferation and tumor cell stemness of colon cancer cells through the transcription and regulation of ROBO2

Article

Author: Jiang, Yahui ; Tang, Yunhao

SALL4 is a transcription factor highly expressed in diverse cancers and is implicated in the development of cancer. SALL4 has been implied to play a cancer-promoting role in colon cancer (CC), but the molecular mechanism remains unclear. Chromatin immunoprecipitation assay and dual-luciferase assay were conducted to verify the binding relationship of SALL4 and ROBO2. qRT-PCR detected the mRNA expression levels of SALL4 and ROBO2, and the flow cytometry analyzed the cell cycle distribution. Western blot examined SALL4 expression, and cell cycle/cell stemness-related proteins. The impact of SALL4 and ROBO2 on the proliferation capacity of cells and tumor cell stemness was elucidated by MTT, colony formation, and sphere-forming assays. SALL4 and ROBO2 were up-regulated in CC, and SALL4 could activate the transcription of ROBO2. Down-regulated SALL4 was able to significantly restrain the proliferation capacity of CC cells and arrest the cell cycle in G0/G1 phase by repressing the expression of cyclin B, cyclin E, and cyclin D1. Besides, the rescue assay results indicated that up-regulated ROBO2 could reverse the repressive impact of down-regulated SALL4 on the proliferation of CC cells and accelerate the progression of the cell cycle, thus promoting the sphere-forming of tumor stem cells. SALL4 advanced the proliferation of CC and cell stemness through direct activation of ROBO2 expression, implied the novel mechanism of SALL4 in CC, and pointed out that SALL4/ROBO2 axis was likely to be a potential target for clinical treatment of CC.

01 Mar 2024·Cell Stem Cell

Thalamocortical organoids enable in vitro modeling of 22q11.2 microdeletion associated with neuropsychiatric disorders

Article

Author: Wigdor, Emilie M ; Sanders, Stephan J ; Popova, Galina ; Larson, H Hanh ; Cadwell, Cathryn R ; Bhaduri, Aparna ; Donohue, Kevin C ; Sohal, Vikaas S ; Kim, Chang N ; Nowakowski, Tomasz J ; Jacquemont, Sebastien ; Pollen, Alex A ; Keefe, Matthew G ; Haussler, David ; Allen, Denise E ; Pavlovic, Bryan J ; Frost, Nicholas A ; Moreau, Clara ; Leonard, Rachel ; Hennick, Kelsey M ; Wang, Jerrick C ; Bearden, Carrie E ; Ross, Jayden ; Paranjape, Neha ; Wiita, Arun P ; Shin, David ; Wu, Sih-Rong

Thalamic dysfunction has been implicated in multiple psychiatric disorders. We sought to study the mechanisms by which abnormalities emerge in the context of the 22q11.2 microdeletion, which confers significant genetic risk for psychiatric disorders. We investigated early stages of human thalamus development using human pluripotent stem cell-derived organoids and show that the 22q11.2 microdeletion underlies widespread transcriptional dysregulation associated with psychiatric disorders in thalamic neurons and glia, including elevated expression of FOXP2. Using an organoid co-culture model, we demonstrate that the 22q11.2 microdeletion mediates an overgrowth of thalamic axons in a FOXP2-dependent manner. Finally, we identify ROBO2 as a candidate molecular mediator of the effects of FOXP2 overexpression on thalamic axon overgrowth. Together, our study suggests that early steps in thalamic development are dysregulated in a model of genetic risk for schizophrenia and contribute to neural phenotypes in 22q11.2 deletion syndrome.

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ROBO2

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