Delving into the Latest Updates on Ro-24-7429 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

Mechanism

RUNX1 antagonists(RUNX family transcription factor 1 antagonists), Tat (HIV) inhibitors(Human Immunodeficiency Virus tat Gene Products inhibitors)

Therapeutic Areas

Cardiovascular DiseasesEndocrinology and Metabolic DiseaseEye Diseases

Active Indication

Choroidal NeovascularizationProliferative retinopathy with diabetes mellitus

Inactive Indication

AIDS-related Kaposi Sarcoma

Originator Organization

F. Hoffmann-La Roche Ltd.

Active Organization

The Schepens Eye Research Institute, Inc.

Inactive Organization

Hoffmann-La Roche, Inc.

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

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Structure

Molecular FormulaC14H13ClN4

InChIKeyLEAKQIXYSHIHCW-UHFFFAOYSA-N

CAS Registry139339-45-0

To study the anti-HIV activity of the various doses of Ro 24-7429 monotherapy based on virologic and immunologic endpoints. To study the safety and tolerance of Ro 24-7429. To explore relationships between exposure to Ro 24-7429 and its metabolites and antiviral activity and drug toxicity. To determine a safe, tolerable, and active dose regimen of Ro 24-7429, and to make preliminary observations of Ro 24-7429 in combination with another antiretroviral nucleoside.
The HIV genome contains a number of genes that regulate viral replication. Control of the activity of these genes and their encoded proteins represents a potential target for development of new antiretroviral drugs. The tat (transactivator of transcription of HIV) antagonist Ro 24-7429 is the first compound for clinical testing that utilizes this approach for therapy of HIV infection.

Start Date-

Sponsor / Collaborator

National Institute of Allergy & Infectious Diseases

[+1]

NCT00002314 / CompletedPhase 2

A Phase II Study of Oral Ro 24-7429 (Tat Antagonist) in Patients With HIV-Related Kaposi's Sarcoma

To study the effects of Ro 24-7429 on tumor growth in patients with HIV-related Kaposi's sarcoma. To study the safety and tolerance, effects on HIV replication, and immunologic effects of Ro 24-7429 in this patient population. To explore relationships between exposure to Ro 24-7429 and its metabolites with its antitumor and antiviral activities and drug toxicity.

Start Date-

Sponsor / Collaborator

Hoffmann-La Roche, Inc.

100 Clinical Results associated with Ro-24-7429

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100 Translational Medicine associated with Ro-24-7429

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100 Patents (Medical) associated with Ro-24-7429

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19

Literatures (Medical) associated with Ro-24-7429

01 Jul 2021·The American Journal of Pathology

Targeting Runt-Related Transcription Factor 1 Prevents Pulmonary Fibrosis and Reduces Expression of Severe Acute Respiratory Syndrome Coronavirus 2 Host Mediators

Article

Author: Krasemann, Susanne ; Pedron, Julien ; Fitzek, Antonia ; Marino, Claudia ; Sepulveda-Falla, Diego ; Kim, Leo A ; Ondruschka, Benjamin ; An, Miranda ; Amarnani, Dhanesh ; Lagares, David ; Arboleda-Velasquez, Joseph F ; Liu, Paul ; Steurer, Stefan ; Ramos, Leslie ; Chmielewska, Natalia ; Bushweller, John H ; Hu, Xinyao ; Chandrahas, Anita ; Heinrich, Fabian ; Whitmore, Hannah A B ; Glatzel, Markus ; O'Hare, Michael ; Delgado-Tirado, Santiago

Pulmonary fibrosis (PF) can arise from unknown causes, as in idiopathic PF, or as a consequence of infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current treatments for PF slow, but do not stop, disease progression. We report that treatment with a runt-related transcription factor 1 (RUNX1) inhibitor (Ro24-7429), previously found to be safe, although ineffective, as a Tat inhibitor in patients with HIV, robustly ameliorates lung fibrosis and inflammation in the bleomycin-induced PF mouse model. RUNX1 inhibition blunted fundamental mechanisms downstream pathologic mediators of fibrosis and inflammation, including transforming growth factor-β1 and tumor necrosis factor-α, in cultured lung epithelial cells, fibroblasts, and vascular endothelial cells, indicating pleiotropic effects. RUNX1 inhibition also reduced the expression of angiotensin-converting enzyme 2 and FES Upstream Region (FURIN), host proteins critical for SARS-CoV-2 infection, in mice and in vitro. A subset of human lungs with SARS-CoV-2 infection overexpress RUNX1. These data suggest that RUNX1 inhibition via repurposing of Ro24-7429 may be beneficial for PF and to battle SARS-CoV-2, by reducing expression of viral mediators and by preventing respiratory complications.

01 Apr 2001·Journal of VirologyQ2 · MEDICINE

Inhibitors of Human Immunodeficiency Virus Type 1 Reverse Transcriptase Target Distinct Phases of Early Reverse Transcription

Q2 · MEDICINE

Article

Author: Lott, William B. ; Hooker, C. William ; Harrich, David

ABSTRACTEarly HIV-1 reverse transcription can be separated into initiation and elongation phases. Here we show, using PCR analysis of negative-strand strong-stop DNA [(−)ssDNA] synthesis in intact virus, that different reverse transcriptase (RT) inhibitors affect distinct phases of early natural endogenous reverse transcription (NERT). The effects of nevirapine on NERT were consistent with a mechanism of action including both specific and nonspecific binding events. The nonspecific component of this inhibition targeted the elongation reaction, whereas the specific effect seemed principally to be directed at very early events (initiation or the initiation-elongation switch). In contrast, foscarnet and the nucleoside analog ddATP inhibited both early and late (−)ssDNA synthesis in a similar manner. We also examined compounds that targeted other viral proteins and found that Ro24-7429 (a Tat antagonist) and rosmarinic acid (an integrase inhibitor) also directly inhibited RT. Our results indicate that NERT can be used to identify and evaluate compounds that directly target the reverse transcription complex.

10 Jun 1999·AIDS Research and Human RetrovirusesQ4 · MEDICINE

Effect of Insulin-Like Growth Factor I on HIV Type 1 Long Terminal Repeat-Driven Chloramphenicol Acetyltransferase Expression

Q4 · MEDICINE

Article

Author: Colby-Germinario, S. P. ; Mak, J. ; Acel, A. ; Davison, K. ; Faust, E. ; Kleiman, L. ; Chandok, R. ; Germinario, Ralph J. ; Wainberg, M. A.

In this study, we have investigated the ability of insulin-like growth factor I (IGF-I) to inhibit HIV long terminal repeat (LTR)-driven gene expression. Using COS 7 cells cotransfected with tat and an HIV LTR linked to a chloramphenicol acetyltransferase (CAT) reporter, we observed that physiological levels of IGF-I (10(-9) M) significantly inhibited CAT expression in a concentration- and time-dependent manner. IGF-I did not inhibit CAT expression in COS 7 cells transfected with pSVCAT, and did not affect CAT expression in the absence of cotransfection with tat. Transfection of HIV-1 proviral DNA into COS 7 cells +/- IGF-I resulted in a significant decrease (p < 0.05) in infectious virion production. Both IGF-I and Ro24-7429 inhibited LTR-driven CAT expression, while TNF-alpha-enhanced CAT expression was not affected by IGF-I. On the other hand, a plasmid encoding parathyroid hormone-related peptide exhibited dramatic additivity of inhibition of CAT expression in COS 7 cells. Finally, we show that in Jurkat or U937 cells cotransfected with HIVLTRCAT/tat, IGF-I significantly inhibited CAT expression. Further, interleukin 4 showed in U937 cells inhibition of CAT expression that was not additive to IGF-I induced inhibition. Our data demonstrate that IGF-I can specifically inhibit HIVLTRCAT expression. This inhibition may occur at the level of the tat/TAR interaction. Finally, this IGF-I effect is seen in target cell lines and similar paths of inhibition may be involved in the various cell types employed.

100 Deals associated with Ro-24-7429

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB16062

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Choroidal Neovascularization	Preclinical	US	The Schepens Eye Research Institute, Inc.	01 May 2022
Proliferative retinopathy with diabetes mellitus	Preclinical	US	The Schepens Eye Research Institute, Inc.	01 May 2022
AIDS-related Kaposi Sarcoma	Discovery	US	Hoffmann-La Roche, Inc.	31 Aug 2001