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podophyllotoxin (Warticon Cream / Warix / Warticon)

✓ Approved

Rottapharm Madaus · 治疗药物

什么是 podophyllotoxin？

podophyllotoxin 是一种治疗药物，由Rottapharm Madaus研发。该药已获批，用于治疗相关适应症，给药途径：Topical。

药物档案

商品名Warticon Cream, Warix, Warticon
公司Rottapharm Madaus
给药途径Topical
状态Approved
来源： ClinicalTrials.gov, Rottapharm Madaus

治疗适应症

podophyllotoxin 针对 1 个适应症，涉及 1 个治疗领域。

治疗领域疾病/病症分期
Infections and infestationsPapilloma viral infection✓ Approved

相关研究文献

PubMedScience (New York, N.Y.)2026-07-30

Enabling sustainable supply of the essential cancer medicines etoposide and teniposide in yeast.

Shen Siyu S, Hu Xue X, Li Dan D, Tong Yuru Y et al.

Lignans constitute a diverse family of plant metabolites with therapeutic potential. Among them, podophyllotoxin-type aryltetralin lignans serve as precursors for etoposide and teniposide. Etoposide is an essential anticancer medicine approved for first-line treatment of small cell lung cancer, whereas teniposide is used for treatment of leukemia and some brain tumors. Currently, these drugs depend on extraction of precursors from the endangered plant Sinopodophyllum hexandrum, followed by chemical transformations. By identifying key glycosyltransferases and executing more than 60 genetic edits involving 45 heterologous enzymes, the complex biosynthetic pathway of podophyllotoxin-type lignans was reconstructed in yeast. In this study, we established a chemoenzymatic route that streamlines the synthesis of etoposide and teniposide through a single chemical step from biosynthetic precursor 4'-demethyl-epipodophyllotoxin-4-O-glucoside, which enables a secure supply chain of these essential medicines.

PMID 42531388
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PubMedPhytomedicine : international journal of phytotherapy and phytopharmacology2026-07-28

Podophyllotoxin induced renal toxicity by triggering fatty acid oxidation dysfunction and ferroptosis in rats on the basis of the toxicological evidence chain (TEC) concept.

Li Xuejiao X, Cao Aijia A, Hu Bin B, Jiang Tao T et al.

Drug nephrotoxicity is a critical concern in drug safety assessment. Podophyllotoxin (PPT) has clear antitumor activity, but its clinical application is limited by nephrotoxicity, the underlying mechanisms of which remain unclear. Employing our innovative toxicological evidence chain (TEC) concept, this study aimed to elucidate the mechanisms underlying PPT-induced nephrotoxicity through a multi-omics approach. Rats were administered PPT at 10 or 20 mg/kg by gavage for 4 days. Behavioral and appearance changes were observed to obtain injury phenotype evidence (IPE). Renal injury was assessed by histopathology and serum biochemical parameters as adverse outcome evidence (AOE). Toxic event evidence (TEE) was obtained by integrating TMT-based proteomics, acetylated proteomics, and targeted metabolomics, combined with functional validation using Western blot, quantitative real-time PCR, and ferroptosis-specific interventions (Fer-1/Erastin). PPT caused renal injury and abnormalities in biochemical parameters in rats (AOE). PPT downregulated SIRT3, reduced LKB1 deacetylation, and inhibited AMPK activity, thereby decreasing the expression of p-ACC1, PPARα, and PGC-1α, leading to fatty acid oxidation (FAO) dysfunction and abnormal lipid accumulation (TEE). Concurrently, PPT suppressed Nrf2, HO-1, and GPX4, disrupting the antioxidant system; downregulated GCLM and GSS, interfering with GSH metabolism; and induced iron overload and lipid peroxidation, triggering ferroptosis (TEE). Functional validation experiments further demonstrated that the ferroptosis-specific inhibitor Fer-1 significantly reversed PPT-induced renal injury, whereas the ferroptosis inducer Erastin exacerbated the injury, confirming the key mediating role of ferroptosis in PPT-induced nephrotoxicity. This study initially revealed that PPT caused FAO dysfunction via the SIRT3-LKB1-AMPK-ACC-PPARα/PGC-1α axis, and triggered ferroptosis through the Nrf2-HO-1/GPX4 and GCLM-GSS-GSH/GPX4 axes, thereby leading to nephrotoxicity. These findings provide new targets for the prevention and treatment of PPT-induced nephrotoxicity.

PMID 42508182
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PubMedDermatology and therapy2026-07-27

Adverse Effects of Treatments for Anogenital Warts in Non-immunocompromised Adults: A Network Meta-analysis of Randomized Controlled Trials.

Saib Réda R, Joly Elisa E, Fouere Sébastien S, Derancourt Christian C et al.

International guidelines for the management of anogenital warts (AGWs) propose multiple first-line options but do not prioritize treatments based on safety or tolerability. This study aimed to compare the safety profiles of topical, systemic, and ablative treatments used for external AGWs in immunocompetent adults. A systematic review and frequentist network meta-analysis of randomized controlled trials published through August 2025 was performed. Adverse events (AEs) were classified as low-, moderate-, or high-grade local AEs (LGL, MGL, HGL) and low-grade general AEs (LGG). Relative risks were estimated using random-effects models with placebo as the reference. We included 107 RCTs involving 12,423 participants. Ablative procedures were associated with higher rates of moderate-to-severe local AEs compared with topical therapies. Among topical treatments, imiquimod 5% and cidofovir cream were associated with lower rates of severe AEs, whereas podophyllotoxin was more often associated with LGL. SUCRA rankings placed topical treatments above ablative therapies in terms of tolerability. Cidofovir cream demonstrated the best safety profile, followed by imiquimod 5%. This network meta-analysis highlights significant differences in tolerability across AGW treatments and offers a comparative framework for patient-centered therapeutic decision-making. It also emphasizes the need for standardized AE reporting in future trials.

PMID 42507080
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PubMedThe Journal of steroid biochemistry and molecular biology2026-07-25

Podophyllotoxin induces testicular toxicity via the microbiota-gut-testis axis based on the toxicological evidence chain concept.

Shao Yuanyang Y, Wang Yu Y, Dai Yihang Y, Wang Lei L et al.

Podophyllotoxin (PPT), a natural lignan with well-established antitumor efficacy and well-documented ovarian toxicity, was first investigated for its potential testicular toxicity in male Sprague-Dawley rats, following the guidance of the Toxicological Evidence Chain (TEC) framework. Through an integrated approach combining physiological and pathological phenotyping, targeted metabolomics of intestinal contents, serum, and testicular tissues, testicular transcriptomics, and 16S rDNA sequencing of gut microbiota, we systematically delineated the injury evidence chain induced by PPT. Oral administration of PPT (20 mg/kg/day for 4 days) elicited marked systemic toxicity, including reduced body weight and food intake, alongside clinical signs such as nasal hemorrhage and diarrhea. Testicular toxicity was evident from decreased testicular weight and organ index, histopathological impairments-including seminiferous tubule distortion, fibrosis, and germ cell apoptosis-and compromised sperm quality. Serum levels of testosterone (T), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were significantly suppressed. Concurrently, colonic injury was observed alongside gut dysbiosis, characterized by a reduction in Lactobacillus and enrichment of Proteus and Escherichia-Shigella. Multi-tissue metabolomics consistently identified disruption of vitamin B6 metabolism, with downregulation of pyridoxine, pyridoxamine, and 4-pyridoxic acid, while transcriptomic analysis revealed suppression of steroidogenic genes (Star, Cyp11a1, Cyp17a1). These findings collectively indicate that PPT induces testicular injury via the microbiota-gut-testis (MGT) axis.

PMID 42498206
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PubMedInternational journal of pharmaceutics2026-07-24

CD44-targeted hyaluronic acid-podophyllotoxin micelles with dual-stimuli responsiveness for lung cancer therapy.

Yang Chunpeng C, Wu Mengdi M, Li Min M, Niu Wenbin W et al.

Clinical application of podophyllotoxin (PPT) is significantly hampered by poor aqueous solubility and considerable systemic toxicity. Herein, we engineered dual-targeting and dual-cleavable prodrug micelles (HPMs) by conjugating PPT to hyaluronic acid (HA) backbone via a flexible, dual-responsive spacer, adipic dihydrazide-3,3'-dithiodipropionic acid (ADH-DTDPA). In vitro, HPMs demonstrated efficient CD44-mediated internalization in NCI-H1299 cells and rapidly disassembled under tumor microenvironment (TME) conditions (pH 5.0/GSH). Crucially, microscale thermophoresis (MST) provided quantitative evidence of the targeting mechanism, revealing a high binding affinity (KD = 15.3 μM) for the CD44 receptor. In vivo, this design achieved effective accumulation of the micelles at tumor sites. Notably, HPMs (10 mg/kg) achieved superior tumor inhibition compared to free PPT (15 mg/kg) without inducing hepatotoxicity or nephrotoxicity. These findings provide a safe delivery strategy to overcome the clinical limitations of PPT and offer quantitative molecular insights into the rational design of targeted nanomedicines for lung cancer therapy.

PMID 42492642
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PubMedAnnals of medicine and surgery (2012)2026-07-11

The clinical effectiveness and safety of imiquimod versus podophyllotoxin in the topical treatment of condylomata acuminata: a systematic review and meta-analysis.

Maqsood Musab M, Nadeem Ali Ahmad AA, Shahid Abdullah A, Ali Muhammad Khan Buhadur MKB et al.

Imiquimod (IMQ) and podophyllotoxin (PDX) are two of the most common self-applied topical therapies for condyloma acuminatum. This review aims to directly compare their clinical effectiveness and safety profiles. Records from two databases and two trial registers were screened for eligibility. The Mantel-Haenszel method was used for statistical analysis, using a fixed- or random-effects model depending on the calculated heterogeneity. Five studies, two RCTs and three cohorts, were included. There was no statistically significant difference in the clinical effectiveness (RR = 0.98; 95% CI: 0.85-1.13; P = 0.74) and adverse effects (RR = 1.06; 95% CI: 0.73-1.53; P = 0.78) between IMQ and PDX. Subgroup analysis revealed a higher frequency of adverse effects with IMQ compared to PDX in adults (RR = 1.22; 95% CI: 1.03-1.46; P = 0.02) and a lower frequency in children (RR = 0.51; 95% CI: 0.27-0.99; P = 0.05), with a statistically significant difference between these two subgroups (P = 0.01). The reviewed studies suggested that the time to complete clearance was comparable, wart recurrence was higher, and the time to recurrence was shorter in IMQ compared to PDX. IMQ may be slower in achieving complete clearance but better in preventing wart recurrence in vaccinated individuals. IMQ has comparable clinical effectiveness, more frequent adverse effects in adults, and less frequent adverse effects in children compared to PDX. Additionally, IMQ's lower wart recurrence may suggest a potential benefit in vaccinated individuals. Thus, IMQ may be slightly better than PDX in these populations, which warrants further research. Nevertheless, the utilized studies had small sample sizes and inadequate power to draw reasonable conclusions (low certainty).

PMID 42433763
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