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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

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

PubMedFrontiers in microbiology2026-09-02

Fungal colonization and candidate metabolite-mediated toxicity of Fusarium solani KMZW-1 against adult Bactrocera dorsalis.

Li Huiqin H, Zhao Zhiyi Z, Wu Mingqi M, Shi Chunlan C et al.

This study examined the interaction between Fusarium solani KMZW-1 and adult Bactrocera dorsalis, with emphasis on cuticular colonization, adult-stage pathological effects, and candidate metabolite-mediated toxicity. KMZW-1 showed Fusarium-like colony and conidial morphology and colonized mainly tarsal setae, joints, and recessed cuticular regions, where fungal conidia and hyphae progressively accumulated over time. Fungal treatment reduced adult survival in a concentration-dependent manner (P < 0.001) and lowered egg production per female, likely due to reduced male survival and fewer mating opportunities, whereas egg hatchability, larval pupation, and adult emergence of offspring were not significantly affected (P > 0.05). Untargeted LC-MS/MS profiling annotated 3073 metabolites, and candidate secondary metabolites were prioritized using pathway assignment, CAS-confirmed identity, normalized peak-area abundance, reported biological activity and commercial availability. Among coumarin, umbelliferone and podophyllotoxin, podophyllotoxin showed the lowest 24 h LC50 values against adult flies, at 24.33 μg mL-1 for females and 21.03 μg mL-1 for males. These results indicate that KMZW-1 produces a reproducible surface-colonization-associated adult-stage phenotype in B. dorsalis. Podophyllotoxin should be interpreted as a prioritized candidate with confirmed topical toxicity, not as a confirmed in vivo virulence determinant. Further work is required to confirm metabolite identity with authentic standards, quantify metabolite production during infection, determine internal invasion dynamics, and evaluate mode of action and non-target safety.

PMID 42682651
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PubMedMolecular horticulture2026-09-02

Deciphering podophyllotoxin-mediated defense against downy blight in Litchi chinensis Sonn. via integrated metabolomics and transcriptomics.

Liu Hailun H, Shi Fachao F, Wen Yingjie Y, Jiang Yonghua Y et al.

Lychee (Litchi chinensis Sonn.) is a commercially important subtropical fruit. Lychee downy blight (LDB), caused by Peronophythora litchii, poses a major threat to lychee production. Here, we identified the LDB-resistant cultivar Yurong (YR) and the susceptible cultivar Guiwei (GW) from 288 global lychee germplasms. Widely targeted metabolomics analysis revealed a striking accumulation of podophyllotoxin (PTOX) in YR. Both in vitro and in vivo assays demonstrated that PTOX effectively inhibited the growth of P. litchii. Further investigation identified LcOMT1 as a key gene encoding an O-methyltransferase (OMT) in the phenylpropanoid pathway. In resistant cultivars, a 773-bp insertion mutation (Hap3 haplotype) in the LcOMT1 promoter enhanced its transcriptional activity. Transgenic approaches using hairy roots in lychee showed that the overexpression of either LcOMT1 or the Hap3 haplotype led to increased PTOX biosynthesis and enhanced resistance to P. litchii. These results demonstrate that the Hap3-mediated upregulation of LcOMT1 drives PTOX accumulation, establishing a crucial defense mechanism against LDB. This study provides new insights into the genetic and metabolic regulatory network underlying lychee resistance to LDB. This study may also lay a theoretical foundation for the development of PTOX-based biopesticides and offer valuable genetic resources for breeding LDB-resistant lychee cultivars.

PMID 42681695
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PubMedInternational journal of molecular sciences2026-08-27

From Aryltetralin Anticancer Scaffolds to Host-Directed Bioactivities: A Mechanism-Based Review of Lignans and Neolignans.

Xie Yuhan Y, Tang Kun K, Coghi Paolo P

Lignans and related neolignans are a diverse class of phenolic natural products with broad biological activities and great potential for pharmaceutical applications. This article summarizes representative subclasses of lignans and compares their antitumor and antioxidant properties from a structural and mechanistic perspective. Aryltetrahydronaphthalene lignans, represented by podophyllotoxin and its semi-synthetic derivatives, provide the clearest baseline for their mechanism of action by disrupting microtubules and inhibiting topoisomerase II. Other subclasses, including dibenzylbutyrolactone, arylnaphthalene, dibenzocyclooctadiene, furofuran lignans, glycosides, and bisphenolic neolignans, exhibit anticancer and redox-regulating effects. Future research should focus on linking structural diversity with validated molecular targets, pharmacokinetic properties, and in vivo efficacy to better define their translational potential.

PMID 42653249
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PubMedEnvironmental toxicology and pharmacology2026-08-14

Molecular mechanisms of podophyllotoxin-induced subacute kidney injury: Oxidative stress-mediated activation of the TRPM2-NOD-NF-κB pathway.

Chen Lulu L, Chen Zilong Z, Li Xinze X, Jiang Tao T et al.

Podophyllotoxin (PPT) has antitumour activity but may cause nephrotoxicity through incompletely defined mechanisms. Male Sprague-Dawley rats received oral PPT (5 or 10 mg/kg/day) for 5 days. Renal injury was evaluated by biochemical, histopathological, Raman, metabolomic, transcriptomic, targeted proteomic, and molecular analyses, followed by validation in NRK-52E cells. PPT at 10 mg/kg reduced 24-h urine output (p < 0.05) and increased serum urea (p < 0.05), uric acid (p < 0.001), KIM-1 (p < 0.001), and lipocalin-2 (p < 0.0001). Renal GSH and CAT decreased (p < 0.001 and p < 0.01, respectively), accompanied by tubular injury, collagen deposition, and apoptosis. Trpm2 and inflammatory and matrix-remodelling genes were upregulated. PRM identified reduced LDHC, HK3, and MGST2 abundance. JNJ-28583113 attenuated PPT-induced ROS accumulation, apoptosis, Nod1/Nod2 expression, and NF-κB p65 phosphorylation. PPT induces subacute kidney injury involving oxidative stress and TRPM2-NOD-NF-κB-related inflammatory signalling.

PMID 42600997
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PubMedInternational journal of molecular sciences2026-08-13

ROS-Responsive Micelles Loaded with Podophyllotoxin Inhibit Tumor Growth via ROS Self-Amplification and Regulation of Survivin and p21 Expression.

Song Shuaiheng S, Shao Qiang Q, Liang Siyi S, Du Haoyang H et al.

Podophyllotoxin (PPT) inhibits tumors such as lung cancer and breast cancer. However, it has poor water solubility and causes gastrointestinal dysfunction and bone marrow suppression, which severely limit its clinical application. Based on the differential reactive oxygen species (ROS) levels between tumor microenvironments and normal tissues, we designed and constructed a ROS-responsive micelle delivery system, successfully fabricating blank micelles (M) and PPT-loaded micelles (M@PPT). Both micelles exhibited good particle size uniformity, colloidal stability, and biosafety. The ROS responsiveness experiment revealed that, after incubating blank micelles (M) with 10 mM H2O2, the particle size increased significantly, and the size distribution broadened. High-performance liquid chromatography (HPLC) confirmed the release of cinnamaldehyde from the micelles upon H2O2 exposure. Additionally, DCFH-DA assays demonstrated that treatment with blank micelles (M) enhanced intracellular ROS levels. In vitro release studies showed that drug-loaded micelles (M@PPT) achieved 77.76% cumulative PPT release within 24 h in a buffer containing 10 mM H2O2, significantly exceeding the release observed in the H2O2-free control group. These results collectively validate the ROS-responsive disintegration of micelles and the subsequent release of cinnamaldehyde. The liberated cinnamaldehyde further amplified intracellular ROS levels, establishing a positive feedback loop that accelerated drug release. Cellular assays revealed superior tumor growth inhibition by M@PPT over free PPT, mediated through apoptosis induction, G2/M phase cell cycle arrest, downregulation of the anti-apoptotic protein Survivin, and upregulation of the p21 protein. In vivo studies further confirmed the enhanced antitumor efficacy and improved biosafety of M@PPT compared to free PPT. This ROS-responsive micellar system, by enabling tumor-targeted drug delivery and controlled release, provides a novel strategy to optimize the clinical utility of podophyllotoxin-based chemotherapeutics.

PMID 42589205
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PubMedColloids and surfaces. B, Biointerfaces2026-08-13

Triple-stimuli-responsive and FGL-1-inhibiting polydopamine nanoparticles for synergistic chemo-photothermal immunotherapy of breast cancer.

Li Min M, Sun Jiao J, An Jie J, Xuan Yang Y et al.

Combination therapies hold significant promise for breast cancer treatment; however, conventional delivery systems often lack precise control over intracellular drug release, limiting delivery efficiency and therapeutic synergy. To address this, we engineered triple stimuli-responsive nanoparticles (HAP/PDA NPs) by coating prodrug HA-PPT (HAP; HA = hyaluronic acid, PPT = podophyllotoxin) with ester and disulfide bonds onto polydopamine (PDA) cores for synergistically combining chemotherapy, photothermal therapy, and immunotherapy. HAP/PDA NPs exhibited tumor microenvironment-responsive drug release triggered by low pH, high glutathione levels, and localized heat, achieving a cumulative PPT release of 90.9% under triple-stimuli conditions. Furthermore, the NPs enhanced photpthermal therapy efficacy by downregulating heat shock protein 70 expression, mitigating thermoresistance. Notably, the mechanism involved suppression of the immune checkpoint fibrinogen-like protein 1 (FGL-1) by HAP/PDA NPs via the JAK2/STAT3 axis, with FGL-1 expression reduced to approximately 40% of the control level, thereby reversing immunosuppression to activate antitumor immunity and drive primary tumor regression. As a result, this multimodal approach enabled complete inhibition of tumor growth in some subjects and maintained high efficacy with a markedly lower PPT dose (one-third of the conventional dose). These findings offer a mechanistic paradigm for designing precision nanomedicines that co-target molecular and immune pathways for improved combination therapy in refractory breast cancer.

PMID 42594792
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