ArticleMolecular cancer therapeutics2009
Development of flexible-heteroarotinoids for kidney cancer.
Article in Molecular cancer therapeutics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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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
22 citing papers in PubMed, 39 citations in OpenAlex.
- Mortalin and PINK1/Parkin-Mediated Mitophagy Represent Ovarian Cancer-Selective Targets for Drug Development.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Review
- Manipulation of metabolic responses enhances SHetA2 efficacy without toxicity in cervical cancer cell lines and xenografts.Gynecologic oncology · 2024Article
- Pharmacodynamics of Cyclin D1 Degradation in Ovarian Cancer Xenografts with Repeated Oral SHetA2 Dosing.The AAPS journal · 2023Article
- SHetA2 Attack on Mortalin and Colleagues in Cancer Therapy and Prevention.Frontiers in cell and developmental biology · 2022Review
- Distinct mechanism of cervical cancer cell death caused by the investigational new drug SHetA2.Frontiers in oncology · 2022Article
- Why is Mortalin a Potential Therapeutic Target for Cancer?Frontiers in cell and developmental biology · 2022Review
- Article
- Novel ovarian cancer maintenance therapy targeted at mortalin and mutant p53.International journal of cancer · 2020Article
- Article
- Physiologically Based Pharmacokinetic Modeling and Tissue Distribution Characteristics of SHetA2 in Tumor-Bearing Mice.The AAPS journal · 2020Article
- Development and validation of a reverse phase HPLC method for SHetA2, a novel anti-cancer drug, in mouse biological samples.Journal of pharmaceutical and biomedical analysis · 2019Article
- Pharmacokinetics and Pharmacodynamics of Escalating Doses of SHetA2 After Vaginal Administration to Mice.Journal of pharmaceutical sciences · 2018Article
- Development of a dietary formulation of the SHetA2 chemoprevention drug for mice.Investigational new drugs · 2018Article
- Role of adaptor protein p66Shc in renal pathologies.American journal of physiology. Renal physiology · 2018Review
- Pharmacokinetics and interspecies scaling of a novel, orally-bioavailable anti-cancer drug, SHetA2.PloS one · 2018Article
- Bioanalytical method development and validation of HPLCUV assay for the quantification of SHetA2 in mouse and human plasma: Application to pharmacokinetics study.Journal of pharmaceutical technology & drug research · 2017Article
- SHetA2 interference with mortalin binding to p66shc and p53 identified using drug-conjugated magnetic microspheres.Investigational new drugs · 2014Article
- Chemoprevention of colon and small intestinal tumorigenesis in APC(min/+) mice by SHetA2 (NSC721689) without toxicity.Cancer prevention research (Philadelphia, Pa.) · 2013Article
- Genotoxicity of the cancer chemopreventive drug candidates CP-31398, SHetA2, and phospho-ibuprofen.Mutation research · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Potential chemopreventive and therapeutic value of the lead Flexible Heteroarotinoid (Flex-Het), SHetA2, was indicated by growth inhibition of multiple cancer cell lines. The objective of this study was to evaluate the SHetA2 mechanism and in vivo activity in kidney cancer. SHetA2 induced apoptosis in the Caki-1 kidney cancer cell line through reduction of Bcl-2 protein and induction of PARP-1 and caspase 3 cleavages, whereas normal kidney epithelial cells exhibited resistance. Both normal and cancerous cells underwent G(1) arrest and loss of Cyclin D1. Tubule differentiation was induced in organotypic cultures and xenograft tumors in association with increases in E-Cadherin mRNA and protein expression. SHetA2 repressed activity of nuclear factor-κB, a transcription factor that regulates apoptosis, Bcl-2, growth, Cyclin D1, differentiation, and E-Cadherin in the opposite manner as SHetA2. Glutathione binding and generation of reactive oxygen species were not required for these activities. Oral SHetA2 inhibited growth in one of two renal cancer xenograft models without causing mortality or weight loss. Structure function analysis of related Flex-Hets for potential improvement of SHetA2 pharmaceutical properties showed that compounds with increased hydrophilicity slightly reduced the growth inhibition efficacy, but retained the differential effect on cancer over normal cells. Flex-Hets and metabolites were not mutagenic in the Ames test. In conclusion, SHetA2 regulates growth, differentiation, and apoptosis in kidney cancer cells through multiple molecular events downstream of nuclear factor-κB repression. Increasing the hydrophilicity of Flex-Hets does not attenuate the differential effect on cancer cells over normal cells, thus offering alternatives for improvement of therapeutic value.
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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.