The purpose of this Phase 2 portion of the study is to use the dose and schedule of RX-5902 identified in the phase 1 to treat subjects with triple negative breast cancer.

Start Date01 Aug 2013

Sponsor / Collaborator

Rexahn Pharmaceuticals, Inc.

100 Clinical Results associated with RX-5902

100 Translational Medicine associated with RX-5902

100 Patents (Medical) associated with RX-5902

Literatures (Medical) associated with RX-5902

01 Jun 2024·Animal Bioscience

RNA helicase DEAD-box-5 is involved in R-loop dynamics of preimplantation embryos

Article

Author: Choi, Youngsok ; Lee, Heeji ; Lee, Hyeonji ; Park, Chanhyeok ; La, Hyeonwoo ; Uhm, Sang Jun ; Hong, Kwonho ; Do, Jeong Tae ; Yoo, Seonho ; Kang, Kiye ; Kwon, Ohbeom ; Song, Hyuk ; Han, Dong Wook

Objective: R-loops are DNA:RNA triplex hybrids, and their metabolism is tightly regulated by transcriptional regulation, DNA damage response, and chromatin structure dynamics. R-loop homeostasis is dynamically regulated and closely associated with gene transcription in mouse zygotes. However, the factors responsible for regulating these dynamic changes in the R-loops of fertilized mouse eggs have not yet been investigated. This study examined the functions of candidate factors that interact with R-loops during zygotic gene activation.Methods: In this study, we used publicly available next-generation sequencing datasets, including low-input ribosome profiling analysis and polymerase II chromatin immunoprecipitation-sequencing (ChIP-seq), to identify potential regulators of R-loop dynamics in zygotes. These datasets were downloaded, reanalyzed, and compared with mass spectrometry data to identify candidate factors involved in regulating R-loop dynamics. To validate the functions of these candidate factors, we treated mouse zygotes with chemical inhibitors using in vitro fertilization. Immunofluorescence with an anti-R-loop antibody was then performed to quantify changes in R-loop metabolism.Results: We identified DEAD-box-5 (DDX5) and histone deacetylase-2 (HDAC2) as candidates that potentially regulate R-loop metabolism in oocytes, zygotes and two-cell embryos based on change of their gene translation. Our analysis revealed that the DDX5 inhibition of activity led to decreased R-loop accumulation in pronuclei, indicating its involvement in regulating R-loop dynamics. However, the inhibition of histone deacetylase-2 activity did not significantly affect R-loop levels in pronuclei.Conclusion: These findings suggest that dynamic changes in R-loops during mouse zygote development are likely regulated by RNA helicases, particularly DDX5, in conjunction with transcriptional processes. Our study provides compelling evidence for the involvement of these factors in regulating R-loop dynamics during early embryonic development.

01 Aug 2022·Cell Reports

The RNA helicase DDX5 cooperates with EHMT2 to sustain alveolar rhabdomyosarcoma growth

Article

Author: Pieroni, Luisa ; Renzini, Alessandra ; Mozzetta, Chiara ; Licursi, Valerio ; Bianconi, Valeria ; Gualtieri, Alberto

Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma of childhood characterized by the inability to exit the proliferative myoblast-like stage. The alveolar fusion positive subtype (FP-RMS) is the most aggressive and is mainly caused by the expression of PAX3/7-FOXO1 oncoproteins, which are challenging pharmacological targets. Here, we show that the DEAD box RNA helicase 5 (DDX5) is overexpressed in alveolar RMS cells and that its depletion and pharmacological inhibition decrease FP-RMS viability and slow tumor growth in xenograft models. Mechanistically, we provide evidence that DDX5 functions upstream of the EHMT2/AKT survival signaling pathway, by directly interacting with EHMT2 mRNA, modulating its stability and consequent protein expression. We show that EHMT2 in turns regulates PAX3-FOXO1 activity in a methylation-dependent manner, thus sustaining FP-RMS myoblastic state. Together, our findings identify another survival-promoting loop in FP-RMS and highlight DDX5 as a potential therapeutic target to arrest RMS growth.

01 Dec 2020·BMC CancerQ2 · MEDICINE

RX-5902, a novel β-catenin modulator, potentiates the efficacy of immune checkpoint inhibitors in preclinical models of triple-negative breast Cancer

Q2 · MEDICINE

ArticleOA

Author: Lang, Julie ; Hartman, Sarah J ; Pelanda, Roberta ; Eckhardt, S Gail ; Eisen, Andrew ; Benaim, Ely ; Bagby, Stacey M ; Diamond, Jennifer R ; Capasso, Anna ; Tentler, John J ; Lee, Young B ; Pitts, Todd M ; Yacob, Betelehem W ; Gittleman, Brian ; Kim, Deog Joong

AbstractBackgroundTriple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with limited systemic treatment options. RX-5902 is a novel anti-cancer agent that inhibits phosphorylated-p68 and thus attenuates nuclear β-catenin signaling. The purpose of this study was to evaluate the ability of β-catenin signaling blockade to enhance the efficacy of anti-CTLA-4 and anti-PD-1 immune checkpoint blockade in immunocompetent, preclinical models of TNBC.MethodsTreatment with RX-5902, anti-PD-1, anti-CTLA-4 or the combination was investigated in BALB/c mice injected with the 4 T1 TNBC cell line. Humanized BALB/c-Rag2nullIl2rγnullSIRPαNOD (hu-CB-BRGS) mice transplanted with a human immune system were implanted with MDA-MB-231 cells. Mice were randomized into treatment groups according to human hematopoietic chimerism and treated with RX-5902, anti-PD-1 or the combination. At sacrifice, bone marrow, lymph nodes, spleen and tumors were harvested for flow cytometry analysis of human immune cells.ResultsThe addition of RX-5902 to CTLA-4 or PD-1 inhibitors resulted in decreased tumor growth in the 4 T1 and human immune system and MDA-MB-231 xenograft models. Immunologic analyses demonstrated a significant increase in the number of activated T cells in tumor infiltrating lymphocytes (TILs) with RX-5902 treatment compared to vehicle (p < 0.05). In the RX-5902/nivolumab combination group, there was a significant increase in the percentage of CD4+ T cells in TILs and increased systemic granzyme B production (p < 0.01).ConclusionsConclusions: RX-5902 enhanced the efficacy of nivolumab in a humanized, preclinical model of TNBC. Several changes in immunologic profiles were noted in mice treated with RX-5902 and the combination, including an increase in activated TILs and a decrease in human myeloid populations, that are often associated with immunosuppression in a tumor microenvironment. RX-5902 also was shown to potentiate the effects of checkpoint inhibitors of CTLA4 and the PD-1 inhibitor in the 4 T-1 murine TNBC model. These findings indicate that RX-5902 may have important immunomodulatory, as well as anti-tumor activity, in TNBC when combined with a checkpoint inhibitor.

100 Deals associated with RX-5902

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Breast Cancer	Phase 2	-	Rexahn Pharmaceuticals, Inc.	-
Advanced Malignant Solid Neoplasm	Phase 1	United States	Rexahn Pharmaceuticals, Inc.	01 Aug 2013
Triple Negative Breast Cancer	Phase 1	United States	Rexahn Pharmaceuticals, Inc.	01 Aug 2013
Melanoma	Phase 1	United States	Rexahn Pharmaceuticals, Inc.	-
Pancreatic Cancer	Phase 1	United States	Rexahn Pharmaceuticals, Inc.	-
Renal Cell Carcinoma	Phase 1	United States	Rexahn Pharmaceuticals, Inc.	-

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02003092 (ASCO_GI2016)	Phase 1	Pancreatic Cancer	18	Supinoxin (RX-5902)	cekfybaosj(lujsvfpeau) = kryxuarwwt uuzocvroqt (rqoxeotuuk ) View more	Positive	01 Feb 2016
				Gemcitabine	fymrwfqkwx(oowpyofdlh) = wfywikedrq ntpilndyba (agiohxuicr ) View more
NCT02003092 (ASCO_GU2016)	Phase 1/2	Renal Cell Carcinoma	18	Supinoxin (RX-5902)	iyaqyepamu(cyyvvmlurz) = wjqyzymksv zlddjmrenj (xjjqockqyl ) View more	Positive	10 Jan 2016
				Sunitinib	llrwlefgnc(qenemekfcd) = ufgiquqxnw tjxmtnsfmi (ctnzojcruy )

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