A Double-blind Placebo Controlled, Randomized, Phase II Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of Twice Daily Topical Applications of AP611074 5% Gel for up to 16 Weeks in Condyloma Patients

This is a double-blind placebo controlled, randomized, phase 2 study to assess the safety, tolerability, pharmacokinetics and efficacy of twice daily topical applications of AP611074 5% Gel for up to 16 weeks in condyloma patients

Start Date01 Jan 2016

Sponsor / Collaborator

Vaxart, Inc.

NCT01532102

/ CompletedPhase 1/2

A Double-blind, Placebo Controlled, Randomized, Phase IIa Study to Assess the Safety, Tolerability, Efficacy, and Pharmacokinetics of Repeated Topical Applications Over 42 Days of AP611074 5% Gel in Condyloma Patients

The purpose of this study is to determine the safety, tolerability and efficacy of the topical application of AP611074 5% gel during 6 weeks on ano-genital warts caused by human papillomavirus (HPV).

Start Date28 Feb 2012

Sponsor / Collaborator

Anaconda Pharma SASU

100 Clinical Results associated with HPV E2

100 Translational Medicine associated with HPV E2

0 Patents (Medical) associated with HPV E2

Literatures (Medical) associated with HPV E2

01 Jan 2025·Journal of Medical Virology

FGFR3 Upregulates Interferon‐Stimulated Genes Via the JAK1‐STAT1 Signaling Pathway in HPV2 E2 Stable Expressing Keratinocytes

Article

Author: Wei, Xuanjin ; Xie, Fang ; Qi, Jiayue ; Li, Chengxin ; Guo, Qingqing

ABSTRACTHuman papillomavirus (HPV) infections are prevalent skin infectious diseases. While there are no specific anti‐HPV drugs available, understanding the viral mechanisms could lead to novel therapeutic strategies. Verruca vulgaris, a common HPV infection, is frequently encountered in dermatological clinics. The HPV E2 protein, an early viral protein, has been implicated in high‐risk HPV infections by interacting with fibroblast growth factor receptor 3 (FGFR3) to inhibit viral DNA replication. However, the role of HPV E2 and FGFR3 in low‐risk HPV infections remains elusive. Our study takes HPV2, a common subtype of verruca vulgaris, to explore the proliferation and immune regulatory effects of HPV2 E2 on keratinocytes. By overexpressing FGFR3 in HPV2 E2 stable expressing keratinocytes, we assessed changes in interferon‐stimulated genes (ISGs) level and cell proliferation. Our findings revealed that HPV2 E2 induced phosphorylation of FGFR3 could activate JAK1‐STAT1 pathway, thereby enhancing antiviral immunity through the upregulation of ISGs. Furthermore, we observed co‐localization and interaction between FGFR3 and HPV2 E2 in keratinocytes. In conclusion, our study underscores the crucial role of FGFR3 in innate antiviral immunity against HPV2 infection in keratinocytes. These findings may provide a potential therapeutic target for HPV infections.

01 Dec 2024·Steroids

Palladium catalysed cross coupling reactions on 2,3-isoxazol-17α-ethynyltestosterone, their anti-cancer activity, molecular docking studies and ADMET analysis

Article

Author: Srivastava, Sanjay ; Yadav, Astha ; Singh, Saurabh Kumar ; Pratap Singh, Ranvijay ; Verma, Anmol ; Prakash, Rohit ; Sethi, Arun

In the current study, the Sonogashira coupling reaction of danazol with aryl halides was carried out, yielding new aryl substituted danazol derivatives. The synthetic compounds were examined for anti-cancer potential on the HeLa human cervical cancer cell line, and they showed promising cytotoxic action. Synthesized compounds 2, 4 and 5 inhibited the growth of HeLa cervical cancer cells, potentially making them effective anti-cancer drugs in the future. Furthermore, molecular docking studies were performed to evaluate the inhibitory impact of danazol derivatives on the Human Papillomavirus (HPV) target protein (1F9F). The docking results showed a significant inhibitory action against the cervical cancer protein (1F9F). The binding energy (ΔG) values of 1, 2, 3, 4 and 5 against the protein 1F9F were -8.01, -8.70, -9.43, -9.58 and -9.75 kcal/mol, indicating a high affinity of the synthesized compounds to bind with the HPV target proteins compared to their parent compound danazol (1). ADMET analyses of all derivatives have also been carried out.

12 Oct 2022·Cancer Biomarkers

Combined HPV 16 E2 and L1 methylation predict response to treatment with cidofovir and imiquimod in patients with vulval intraepithelial neoplasia

Article

Author: Hurt, Christopher Nicholas ; Tristram, Amanda ; Alvarez-Mendoza, Carlos ; Powell, Ned ; Nedjai, Belinda ; Jones, Sadie

BACKGROUND: Topical cidofovir and imiquimod can effectively treat approximately 55% of patients with vulval intraepithelial neoplasia (VIN), thus avoiding the need for surgery. Human papillomavirus (HPV) E⁢2 gene methylation predicts response to treatment but a methylation measurement is only obtainable in approximately 50% of patients. OBJECTIVE: This work aimed to determine if the applicability and predictive power of the E⁢2 methylation assay could be improved by combining it with the components of a host and viral DNA methylation panel (S5) that has been found to predict disease progression in patients with cervical intraepithelial neoplasia. METHODS: HPV E2 methylation and S5 classifier score were measured in fresh tissue samples collected pre-treatment from 132 patients with biopsy-proven VIN grade 3 who participated in a multicentre clinical trial and were randomised to treatment with cidofovir or imiquimod. RESULTS: Combining HPV16 E⁢2 and HPV16 L⁢1 methylation provides a biomarker that is both predictive of response to topical treatment and that can produce a clinically applicable result for all patients. Patients with HPV 16 L⁢1ℎ𝑖𝑔ℎand HPV 16 E⁢2ℎ𝑖𝑔ℎ (36/132 (27.3%)) were more likely to respond to treatment with cidofovir (12/15 (80.0%)) than imiquimod (9/21 (42.9%)) (p= 0.026). Patients with HPV 16 L⁢1𝑙𝑜𝑤or HPV 16 E⁢2𝑙𝑜𝑤 (including those with no HPV/unassessable methylation) were more likely to respond to imiquimod: 23/50 (46.0%) vs 31/46 (67.4%) (p= 0.035). CONCLUSIONS: Combined HPV E⁢2 and L⁢1 methylation is a potential predictive marker in treatment for all patients with VIN. These findings justify validation in a prospective trial.

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