ArticleScientific reports2016
Novel small molecules targeting ciliary transport of Smoothened and oncogenic Hedgehog pathway activation.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
10 citing papers in PubMed, 18 citations in OpenAlex.
- A reversible state of hypometabolism in a human cellular model of sporadic Parkinson's disease.Nature communications · 2023Article
- Primary cilia and SHH signaling impairments in human and mouse models of Parkinson's disease.Nature communications · 2022Article
- Differential gene expression identifies a transcriptional regulatory network involving ER-alpha and PITX1 in invasive epithelial ovarian cancer.BMC cancer · 2021Article
- GPRASP proteins are critical negative regulators of hematopoietic stem cell transplantation.Blood · 2020Article
- Annexin A2 could enhance multidrug resistance by regulating NF-κB signaling pathway in pediatric neuroblastoma.Journal of experimental & clinical cancer research : CR · 2017Article
- Primary cilia as a novel horizon between neuron and environment.Neural regeneration research · 2017Review
- Smoothened is a poor prognosis factor and a potential therapeutic target in glioma.Scientific reports · 2017Article
- INPP5E regulates phosphoinositide-dependent cilia transition zone function.The Journal of cell biology · 2017Article
- Zfp423 Regulates Sonic Hedgehog Signaling via Primary Cilium Function.PLoS genetics · 2016Article
- Definition of a critical spatiotemporal window within which primary cilia control midbrain dopaminergic neurogenesis.Neurogenesis (Austin, Tex.) · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Trafficking of the G protein-coupled receptor (GPCR) Smoothened (Smo) to the primary cilium (PC) is a potential target to inhibit oncogenic Hh pathway activation in a large number of tumors. One drawback is the appearance of Smo mutations that resist drug treatment, which is a common reason for cancer treatment failure. Here, we undertook a high content screen with compounds in preclinical or clinical development and identified ten small molecules that prevent constitutive active mutant SmoM2 transport into PC for subsequent Hh pathway activation. Eight of the ten small molecules act through direct interference with the G protein-coupled receptor associated sorting protein 2 (Gprasp2)-SmoM2 ciliary targeting complex, whereas one antagonist of ionotropic receptors prevents intracellular trafficking of Smo to the PC. Together, these findings identify several compounds with the potential to treat drug-resistant SmoM2-driven cancer forms, but also reveal off-target effects of established drugs in the clinics.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.