Drug Database
PO

podophyllotoxin (Warticon Cream / Warix / Warticon)

✓ Approved

Rottapharm Madaus · therapeutic agent

What is podophyllotoxin?

podophyllotoxin is a therapeutic agent developed by Rottapharm Madaus. It is approved for therapeutic indications via topical.

Drug Profile

Brand NamesWarticon Cream, Warix, Warticon
CompanyRottapharm Madaus
RouteTopical
StatusApproved
Sources: ClinicalTrials.gov, Rottapharm Madaus

Therapeutic Indications

podophyllotoxin is developed for 1 unique indication across 1 therapeutic area.

Therapeutic AreaConditionPhase
Infections and infestationsPapilloma viral infection✓ Approved

Related Research Articles

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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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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