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- | NAV-2729 / Navigen
Journal, IO biomarker: Bcl2l12, a novel protein interacting with Arf6, triggers Schwann cell differentiation program. (Pubmed Central) - Jan 3, 2025
Specific inhibition of Arf6 and cytohesins by NAV-2729 and SecinH3, respectively, decreased expression of marker proteins 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) and glial fibrillary acidic protein (GFAP)...The knockdown also led to decreased filamentous actin extents. These results suggest that Arf6 and Bcl2l12 can trigger Schwann cell differentiation, providing evidence for a molecular relay that underlies how Schwann cells differentiate.
- | CPT31 / Navigen
Journal: Electron tomography visualization of HIV-1 virions trapped by fusion inhibitors to host cells in infected tissues. (Pubmed Central) - Nov 19, 2024
The findings of trapped HIV-1 virions in all tissues examined demonstrate a wide distribution of the CPT31 inhibitor, a desirable property for a potential therapeutic. In addition, the presence of virions trapped by spokes, particularly in vascular endothelial cells, demonstrates that the fusion inhibitors can be used as markers for potential HIV-1-target cells within tissues, facilitating the mapping of HIV-1 target cells within the complex cellular milieu of infected tissues.
- | CPT31 / Navigen
Journal: Electron tomography visualization of HIV-1 virions trapped by fusion inhibitors to host cells in infected tissues. (Pubmed Central) - Sep 4, 2024
The finding of trapped HIV-1 virions in all tissues examined demonstrates a wide distribution of the CPT31 inhibitor, a desirable property for a potential therapeutic. In addition, the presence of virions trapped by spokes, particularly in vascular endothelial cells, demonstrates that fusion inhibitors can be used as markers for potential HIV-1-target cells within tissues, facilitating the mapping of HIV-1 target cells within the complex cellular milieu of infected tissues.
- NAV-2729 / Navigen
Identifying the regulatory cascade governing amyloid precursor protein macropinocytosis and subsequent production of amyloid-beta. (Virtual) - Jun 19, 2024 - Abstract #AAIC2024AAIC_1895;
These regulatory proteins could be targeted to modulate APP-lysosomal trafficking and reduce A? production.
- | NAV-2729 / Navigen
Journal: Structural and functional characterization of mycobacterial PhoH2 and identification of potential inhibitor of its enzymatic activity. (Pubmed Central) - Jun 5, 2024
production. In silico inhibitor screening revealed ML141 and NAV_2729 as two potential inhibitors
- NAV-2729 / Navigen
Addiction to Small Gtpase ARF6-Mediated Sphingolipid Homeostasis By AML but Not the Host (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_1789;
In silico inhibitor screening revealed ML141 and NAV_2729 as two potential inhibitors Surprisingly, Tamoxifen-induced whole body KO of Arf6 in adult Arf6 f/f ;Rosa-CreERT 2 mice led to healthy and grossly normal mice with a normal lifespan...Both NAV-2729 and A6-4471 inhibited AML cell line proliferation and reduced primary AML cell colony formation in lower
- NAV-2729 / Navigen
Targeting Small GTPase ARF6 Suppresses AML and Spares Host's Normal Physiology () - Aug 31, 2023 - Abstract #SOHO2023SOHO_403;
High ARF6 expression correlates with worse survival of AML patients. Targeting ARF6 disrupts sphingolipid homeostasis in AML cells, suppresses their proliferation but spares the host's normal physiology.
- | NAV-2729 / Navigen
Journal: Enterovirus 71 enters human brain microvascular endothelial cells through an ARF6-mediated endocytic pathway. (Pubmed Central) - Jul 11, 2023
Murine experiments demonstrated that NAV-2729 significantly alleviated mortality caused by EV71 infection. Our study revealed a new pathway by which EV71 enters the HBMECs and provides new targets for drug development.
- | NAV-2729 / Navigen
Preclinical, Journal: ARF6 is a host factor for SARS-CoV-2 infection in vitro. (Pubmed Central) - Jun 25, 2023
By using a human hepatocarcinoma cell line, Huh-7, which is resistant to the antiviral action of the TMPRSS2 inhibitor camostat, we discovered that SARS-CoV-2 entry is not dependent on dynamin but on cholesterol...In addition, pharmacological inhibition of ARF6 with the small molecule NAV-2729 showed a dose-dependent reduction of viral infection...This highlighted a role for ARF6 in multiple cell contexts. Together, these experiments point to ARF6 as a putative target to develop antiviral strategies against SARS-CoV-2.
- | NAV-2729 / Navigen
Journal: The small molecule inhibitor NAV-2729 has a complex target profile including multiple ADP-ribosylation factor regulatory proteins. (Pubmed Central) - Mar 29, 2023
Finally, our screens identified 48 other possible targets of NAV-2729. These results illustrate the complexities of defining targets of small molecules and identify NAV-2729 as a model PH domain- binding inhibitor.
- | BMS309403 / BMS, NAV-2729 / Navigen
Journal: Pharmacological Inhibition of Lipid Import and Transport Proteins in Ovarian Cancer. (Pubmed Central) - Dec 12, 2022
Our findings indicate that OC cells are very sensitive to lipid deficiency. This dependency should be exploited for development of novel strategies against OC.
- | NAV-2729 / Navigen, thapsigargin / University of Nottingham, Pirbright Institute, SP600125 / BMS
Journal: Blocking the cytohesin-2/ARF1 axis by SecinH3 ameliorates osteoclast-induced bone loss via attenuating JNK-mediated IRE1 endoribonuclease activity. (Pubmed Central) - Nov 9, 2022
Both SecinH3 and silencing of cytohesin-2 inhibit JNK activation and IRE1 endoribonuclease activity, leading to the suppression of osteoclast differentiation. Taken together, our findings add new insights into the regulation between JNK and IRE1, and reveal that inhibiting the cytohesin-2/ARF1/JNK/IRE1 axis might represent a potential new strategy for the treatment of post-menopause osteoporosis.
- | NAV-2729 / Navigen
Journal: Computational and mutational hotspot analysis of mycobacterial inorganic pyrophosphatase and virtual screening of natural compounds to discover contemporary drug candidates: Trilateral approach that explores its GTPase activity. (Pubmed Central) - Jul 9, 2022
Mt-PPa activity is temperature and pH sensitive as the mutation in the His 21 and His 86 residues shift the optimal pH. Virtual screening of 700 compounds from herbal ingredient targets (HITs) subset of zinc database showed ZINC000003979028, ZINC000003870413, ZINC000003870412, ZINC000150338758, ZINC0000070450948, ZINC000150338754, ZINC000095098891, ZINC000000119985 and ZINC000005085286 as the top target hits and Mac0182344 and NAV_2729 as the top GTPase inhibitor that would target and hinders Mt-PPa activity.
- | NAV-2729 / Navigen
Journal: Inhibition of neurogenic contractions in renal arteries and of cholinergic contractions in coronary arteries by the presumed inhibitor of ADP-ribosylation factor 6, NAV2729. (Pubmed Central) - Apr 7, 2022
In coronary arteries, NAV2729 (5 µM) inhibited concentration-dependent contractions induced by carbachol and methacholine...In both vessel types, NAV2729 does not inhibit contractions induced by receptor agonists other than those acting on muscarinic receptors. Addressing effects in other vessels and in other smooth muscle-rich organs merits further attention.
- || NAV-2729 / Navigen
Review, Journal: Does coupling to ADP ribosylation factor 6 explain differences between muscarinic and other receptors in interaction with β-adrenoceptor-mediated smooth muscle relaxation? (Pubmed Central) - Apr 7, 2022
Against this background, we discuss the role of ADP ribosylation factor 6 in cellular responses to G-protein-coupled receptor stimulation. While ADP ribosylation factor 6 apparently is the only promising molecular explanation for the relative resistance of smooth muscle contraction elicited by muscarinic agonists, the existing data are insufficient for a robust conclusion.
- || CPT31 / Navigen
Trial completion, Trial completion date: A Clinical Study of the HIV Drug CPT31 in Healthy Volunteers (clinicaltrials.gov) - Mar 24, 2022
P1, N=32, Completed, Sponsor: Navigen, Inc.
While ADP ribosylation factor 6 apparently is the only promising molecular explanation for the relative resistance of smooth muscle contraction elicited by muscarinic agonists, the existing data are insufficient for a robust conclusion. Enrolling by invitation --> Completed | Trial completion date: Dec 2022 --> Apr 2021
- | CPT31 / Navigen
Trial completion date: A Clinical Study of the HIV Drug CPT31 in Healthy Volunteers (clinicaltrials.gov) - Mar 10, 2022
P1, N=32, Enrolling by invitation, Sponsor: Navigen, Inc.
Enrolling by invitation --> Completed | Trial completion date: Dec 2022 --> Apr 2021 Trial completion date: Apr 2021 --> Dec 2022
- | NSC23766 / University of Oslo, NAV-2729 / Navigen
Journal: A multifactorial assessment of the SRP pathway constituent FtsY as a vital mycobacterial constituent. (Pubmed Central) - Nov 29, 2021
Further ML141 and NAV2729 found to decrease the enzymatic activity of FtsY as well as the mycobacterial growth. Therefore, the conclusive statement of the present manuscript can be stated as the FtsY plays major role mycobacterial cell survival and ML141 and NAV2729 can be used to constrain the SRP pathway.
- | NAV-2729 / Navigen
Journal: ADP ribosylation factor 6 promotes contraction and proliferation, suppresses apoptosis and is specifically inhibited by NAV2729 in prostate stromal cells. (Pubmed Central) - Nov 12, 2021
Significance Statement By knockout of ARF6 in prostate stromal cells, we demonstrate an involvement of ARF6 in promotion of prostate smooth muscle contraction and stromal growth, and define concentration ranges for their ARF6-specific inhibition by NAV2729. Besides the context of benign prostatic hyperplasia and lower urinary tract symptoms, analog ARF6 functions in contraction and growth appear possible in other smooth muscle-rich organs, which merits further attention considering the high clinical relevance of smooth muscle-based diseases.
- NAV-2729 / Navigen
[VIRTUAL] The monomeric GTPase ARF6 is required for smooth muscle contraction and stromal proliferation in the prostate, and is specifically inhibited by NAV2729 (Virtual Room 9) - Apr 27, 2021 - Abstract #EAU2021EAU_387;
- || CPT31 / Navigen
New P1 trial: A Clinical Study of the HIV Drug CPT31 in Healthy Volunteers (clinicaltrials.gov) - Dec 16, 2020
P1, N=32, Enrolling by invitation, Sponsor: Navigen, Inc.
- | CPT31 / Navigen
Journal: Prevention and treatment of SHIVAD8 infection in rhesus macaques by a potent d-peptide HIV entry inhibitor. (Pubmed Central) - Nov 1, 2020
In chronically infected animals with viremia initially controlled by combination antiretroviral therapy (cART), CPT31 monotherapy prevented viral rebound after discontinuation of cART. These data establish CPT31 as a promising candidate for HIV prevention and treatment.
- NAV-2729 / Navigen
[VIRTUAL] Neurogenic smooth muscle contractions of the male detrusor are suppressed by a mechanism which is sensitive to the ADP ribosylation factor 6 (ARF6) inhibitor NAV2729 (Lecture sessions - available at any time every day) - Sep 6, 2020 - Abstract #DGU2020DGU_499;
NAV2729 selectively enhanced neurogenic, but not agonist-induced detrusor contractions, suggesting suppression of contractile neurotransmission in the detrusor by ARF6. Due to its opposing roles in the prostate (inhibition of contraction) and the bladder (promoting contraction), NAV2729 may represent an attractive compound to be tested for treatment of underactive bladder.