ArticleInvestigational new drugs2005
Flexible heteroarotinoids (Flex-Hets) exhibit improved therapeutic ratios as anti-cancer agents over retinoic acid receptor agonists.
Article in Investigational new drugs, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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
28 citing papers in PubMed, 60 citations in OpenAlex.
- Mortalin and PINK1/Parkin-Mediated Mitophagy Represent Ovarian Cancer-Selective Targets for Drug Development.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Prevention of hypertension-induced renal vascular dysfunction through a p66Shc-targeted mechanism.American journal of physiology. Renal physiology · 2025Article
- Targeting HSP70-E7 Interaction With SHetA2: A Novel Therapeutic Strategy for Cervical Cancer.Journal of medical virology · 2024Article
- 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
- Distinct mechanism of cervical cancer cell death caused by the investigational new drug SHetA2.Frontiers in oncology · 2022Article
- SHetA2 Attack on Mortalin and Colleagues in Cancer Therapy and Prevention.Frontiers in cell and developmental biology · 2022Review
- Article
- Vaginal Suppositories Containing SHetA2 to Treat Cervical Dysplasia: Pharmacokinetics of Daily Doses and Preliminary Safety Profile.Journal of pharmaceutical sciences · 2020Article
- 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
- Optimization of a Vaginal Suppository Formulation to Deliver SHetA2 as a Novel Treatment for Cervical Dysplasia.Journal of pharmaceutical sciences · 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
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
The anti-cancer activities and toxicities of retinoic acid (RA) and synthetic retinoids are mediated through nuclear RA receptors (RARs) and retinoid X receptors (RXRs) that act as transcription factors. Heteroarotinoids (Hets), which contain a heteroatom in the cyclic ring of an arotinoid structure, exhibit similar anti-cancer activities, but reduced toxicity in vivo, in comparison to parent retinoids and RA. A new class of Flexible Hets (Flex-Hets), which contain 3-atom urea or thiourea linkers, regulate growth and differentiation similar to RA, but do not activate RARs or RXRs. In addition, Flex-Hets induce potent apoptosis in ovarian cancer and in head and neck cancer cell lines through the intrinsic mitochondrial pathway. In this study, 4 cervical cancer cell lines were growth inhibited by micromolar concentrations of Flex-Hets to greater extents than RAR/RXR active retinoids. The most potent Flex-Het (SHetA2) inhibited each cell line of the National Cancer Institute's human tumor cell line panel at micromolar concentrations. Oral administration of Flex-Hets (SHetA2 and SHetA4) inhibited growth of OVCAR-3 ovarian cancer xenografts to similar extents as administration of a RAR/RXR-panagonist (SHet50) and Fenretinide (4-HPR) in vivo. None of these compounds induced evidence of skin, bone or liver toxicity, or increased levels of serum alanine aminotransferase (ALT) in the treated mice. Topical application of Flex-Hets did not induce skin irritation in vivo, whereas a RAR/RXR-panagonist (NHet17) and a RARgamma-selective agonist (SHet65) induced similar irritancy as RA. In conclusion, Flex-Hets exhibit improved therapeutic ratios for multiple cancer types over RAR and/or RXR agonists.
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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.