The Treatment of Pinworm Infections in Humans (Enterobiasis) with Pyrvinium Chloride and Pyrvinium Pamoate

Beck, J. Walter; Saavedra, David; Antell, G. J.; Tejeiro, B.

doi:10.4269/ajtmh.1959.8.349

Cited by 54 publications

(25 citation statements)

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“…Blocking the Wnt/β-catenin signaling pathway suppresses the progression of MM, which indicates that a potential therapeutic approach would be to intervene in the Wnt/β-catenin pathway (12,13). P y r vi n iu m pa moat e [6 -(d i met hyla m i no) -2-[2-(2,5-dimethyl-1-phenylpyrrol-3-yl) ethenyl]-1-methylquinolinium; PP], commercially known as Povan or Vanquin, is a US Food and Drug Administration (FDA)-approved oral anthelmintic drug (14). It is approved for the treatment of enterobiasis, with a safe human dosage of 5-35 mg/kg/day.…”

Section: Introductionmentioning

confidence: 99%

Anthelmintic pyrvinium pamoate blocks Wnt/β-catenin and induces apoptosis in multiple myeloma cells

Zhu

et al. 2018

Oncol Lett

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Abstract. Multiple myeloma (MM) is a malignancy of the bone marrow. The median survival time of patients with MM is only 5 years, with patients frequently experiencing relapse. Currently, there is no effective therapy for recurrent MM. The results of the present study indicated that pyrvinium pamoate (PP), a US Food and Drug Administration-approved oral anthelmintic drug, exhibited potent antitumor activity in MM cells in vitro. It is demonstrated that PP inhibited MM cell proliferation and mediated apoptosis. Notably, PP markedly promoted the degradation of β-catenin and abrogated its phosphorylation. PP triggered apoptosis in MM cells by inducing the release of cytochrome c and downregulating the expression of myeloid leukemia cell differentiation protein.In addition, PP effectively induced cell death in primary MM cells. In conclusion, PP may be a promising agent for the clinical treatment of MM.

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Section: Introductionmentioning

confidence: 99%

Anthelmintic pyrvinium pamoate blocks Wnt/β-catenin and induces apoptosis in multiple myeloma cells

Zhu

et al. 2018

Oncol Lett

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“…We previously used a cell-based assay of ligand-induced conformational change in AR to identify multiple non-competitive antagonists (6). Here, we evaluate the 2 most potent AR inhibitors, pyrvinium pamoate (PP), a Food and Drug Administration-approved drug (8,9), and harmol hydrochloride (HH), a natural product (10).…”

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confidence: 99%

Non-competitive androgen receptor inhibition in vitro and in vivo

Jones

Bolton

Huang³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

121

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Androgen receptor (AR) inhibitors are used to treat multiple human diseases, including hirsutism, benign prostatic hypertrophy, and prostate cancer, but all available anti-androgens target only ligand binding, either by reduction of available hormone or by competitive antagonism. New strategies are needed, and could have an important impact on therapy. One approach could be to target other cellular mechanisms required for receptor activation. In prior work, we used a cell-based assay of AR conformation change to identify non-ligand inhibitors of AR activity. Here, we characterize 2 compounds identified in this screen: pyrvinium pamoate, a Food and Drug Administration-approved drug, and harmol hydrochloride, a natural product. Each compound functions by a unique, non-competitive mechanism and synergizes with competitive antagonists to disrupt AR activity. Harmol blocks DNA occupancy by AR, whereas pyrvinium does not. Pyrvinium inhibits AR-dependent gene expression in the prostate gland in vivo, and induces prostate atrophy. These results highlight new therapeutic strategies to inhibit AR activity.antagonist ͉ harmol ͉ pyrvinium T he androgen receptor (AR) is a member of the nuclear hormone receptor superfamily, which consists of a large group of ligand-regulated transcription factors. AR is expressed in many tissues and influences an enormous range of physiologic processes such as cognition, muscle hypertrophy, bone density, and prostate growth and differentiation (1). However, AR signaling is directly linked to numerous diseases, including benign prostatic hyperplasia, alopecia, and hirsutism (2). AR signaling also drives the proliferation of prostate cancer, even in the setting of therapies that reduce systemic hormone ligand levels, making AR the major therapeutic target for this malignancy (3).Before ligand binding, AR associates with a complex of cytoplasmic factors and molecular chaperones that maintain the receptor in a high-affinity ligand binding conformation (4). AR signaling is initiated by binding of testosterone or the more potent dihydrotestosterone (DHT). This induces an intramolecular conformation change in AR that brings the amino (N) and carboxy (C) termini into close proximity. This occurs with a t 1/2 of approximately 3.5 min in cells treated with DHT (5), and does not occur in cell lysates (6), suggesting that the induced conformation change is not protein autonomous, but depends on additional cellular factors. Activated AR accumulates in the nucleus, where it binds to DNA as a homodimer at specific androgen response elements to regulate gene expression. Transcriptional control by AR results from complex interactions with positive (i.e., co-activator) and negative (i.e., co-repressor) factors (1). These co-regulatory factors fine-tune AR activity, and AR can even be activated in the absence of ligand by certain cross-talk pathways (7).Although AR activity is highly regulated, with many possible points for intervention, all existing approaches to block AR signaling ultimately target ligand bin...

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“…It can effect a cure rate of nearly 980% . Previous investigators, such as Royer (1956), Miller et al (1958), Bumbalo et al (1958, and Beck et al (1959), have shown the effectiveness of this drug for oxyuriasis given as either multiple doses or as a single dose. Our study has confirmed the previous reports.…”

Section: Discussionmentioning

confidence: 99%

Single-dose Treatment of Oxyuriasis with Pyrvinium Embonate

Desai¹

1962

BMJ

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The Treatment of Pinworm Infections in Humans (Enterobiasis) with Pyrvinium Chloride and Pyrvinium Pamoate

Cited by 54 publications

References 0 publications

Anthelmintic pyrvinium pamoate blocks Wnt/β-catenin and induces apoptosis in multiple myeloma cells

Anthelmintic pyrvinium pamoate blocks Wnt/β-catenin and induces apoptosis in multiple myeloma cells

Non-competitive androgen receptor inhibition in vitro and in vivo

Single-dose Treatment of Oxyuriasis with Pyrvinium Embonate

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