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| 25mg |
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| 50mg |
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| 100mg |
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| Targets |
Arf6; Arf
NAV-2729 targets the small GTPase Arf6 and its guanine nucleotide exchange factor (GEF) BRAG. Arf6 is a member of the ADP-ribosylation factor (Arf) family of small GTPases involved in membrane trafficking, actin cytoskeleton dynamics, and cell signaling. By inhibiting Arf6 activation and BRAG-mediated nucleotide exchange, NAV-2729 blocks Arf6-dependent cellular processes. This mechanism is relevant for studying cancer cell invasion and metastasis. |
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| ln Vitro |
NAV-2729 binds to Arf6 directly. In contrast to Arf6's guanine nucleotide-binding pocket, NAV-2729 is thought to bind to Arf6 at the Arf6 GEF-binding area, according to a structural homology model of the Arf6/Arf6-GEF complex. On Arf6, NAV-2729 prevents guanine nucleotide exchange mediated by GEP100 and ARNO. The application of NAV-2729 to uveal melanoma cells inhibits the cells' ability to grow without anchorage[1]. NAV-2729 is a dual inhibitor of Arf1/Arf6, with a greater affinity for Arf1 than for Arf6. NAV-2729 inhibits both the cytohesin and BRAG-induced and spontaneous activation of Arf6. NAV-2729 is an inhibitor of Arf6's spontaneous activation and of Arf6's GEFs, BRAG2 and ARNO, activating it in solution. At a concentration of 25 μM, which is reported to produce nearly complete inhibition of both spontaneous and GEF-stimulated Arf6 activation in vitro, the inhibitory profile of NAV-2729 is examined. NAV-2729 impedes Δ13Arf6's spontaneous nucleotide exchange by about 15% under the assay conditions. A quarter of the activation of Δ13Arf6 by BRAG2Sec7PH is inhibited by NAV-2729. There is no detectable spontaneous nucleotide exchange in Δ17Arf1. NAV-2729 inhibits Δ17Arf1 activation by BRAG2Sec7PH with a significantly higher efficiency than Arf6 (50%). Nucleotide exchange rates are lowered by 50% in a dose-response experiment when using 10 μM NAV-2729 for Δ17Arf1, but not by 50% when using 25 μM NAV-2729 for Δ13Arf6.
In vitro, NAV-2729 inhibits Arf6 activation and BRAG-mediated nucleotide exchange. The compound blocks Arf6-dependent cellular processes including membrane trafficking, actin remodeling, and cell migration. It has been characterized in biochemical and cell-based assays. NAV-2729 shows specificity for Arf6 over other Arf family members. Detailed in vitro data are available in the primary literature. The compound is a valuable tool for studying Arf6 function. |
| ln Vivo |
In an orthotopic xenograft mouse model of uveal melanoma, systemic treatment of the mice with NAV-2729 inhibits tumorigenesis and tumor growth[1].
In vivo data for NAV-2729 are limited in publicly available sources. Based on its potent in vitro activity against Arf6, the compound is expected to be useful for in vivo studies of Arf6 function in cancer and other diseases. Further studies are needed to fully characterize its in vivo efficacy and pharmacokinetic profile. The compound is a research tool for cell biology. |
| Enzyme Assay |
In vitro Arf6 activation assays for NAV-2729 typically use recombinant Arf6 and BRAG proteins. The compound is dissolved in DMSO and diluted in assay buffer. GTP loading assays measure the exchange of GDP for GTP on Arf6. Reactions are incubated at 30°C for 30-60 minutes, and GTP-bound Arf6 is detected by pull-down assays or fluorescence. IC₅₀ values are calculated from dose-response curves. Controls include DMSO vehicle and known Arf6 inhibitors. Selectivity is assessed against other Arf family members.
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| Cell Assay |
For cell-based assays, cancer cell lines are cultured in appropriate medium. Cells are seeded in multi-well plates and treated with NAV-2729 at various concentrations (0.1-100 μM) for 24-72 hours. Arf6 activation is assessed by pull-down assays. Cell migration is assessed by wound-healing or Transwell assays. Actin remodeling is assessed by phalloidin staining. Cell viability is assessed by MTT or CellTiter-Glo. All treatments include vehicle controls and are performed in triplicate.
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| Animal Protocol |
In vivo, NAV-2729 may be administered to rodents via intraperitoneal (IP) or intravenous (IV) injection. The compound is formulated in a suitable vehicle such as DMSO, PEG, or saline-based solutions. For tumor models, animals bearing Arf6-dependent tumors are dosed at various regimens. Endpoints include tumor volume measurement, survival analysis, and biomarker assessment. Blood and tissue samples are collected for pharmacokinetic and pharmacodynamic analysis. All procedures follow institutional animal care guidelines.
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| ADME/Pharmacokinetics |
NAV-2729 (MW 452.50, C₂₆H₂₈N₄O₃) is an Arf6 inhibitor. The compound is soluble in DMSO. Detailed pharmacokinetic parameters are not extensively reported in publicly available sources. The compound is typically stored at -20°C. Further ADME studies are needed to fully characterize its pharmacokinetic profile. The compound is for research purposes.
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| Toxicity/Toxicokinetics |
NAV-2729 is for research use only and not intended for human therapeutic applications. Standard safety pharmacology and toxicology studies would be required for therapeutic development. The compound should be handled with standard laboratory safety precautions. Toxicity data are limited in publicly available sources.
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| References |
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| Additional Infomation |
NAV2729 is a pyrazolopyrimidine compound with the chemical name 4H-pyrazolo[1,5-a]pyrimidin-7-one, in which the 2, 3, and 5 positions are substituted with benzyl, p-chlorophenyl, and p-nitrophenyl, respectively. It is an inhibitor of ADP ribosylation factor 6 (ARF6), a member of the ADP ribosylation factor family of GTP-binding proteins. NAV2729 exhibits inhibitory activity. It is a pyrazolopyrimidine compound, belonging to the C-nitro group, and is also a monochlorobenzene compound.
NAV-2729 is a research-grade Arf6 inhibitor for studying membrane trafficking, cell migration, and cancer biology. Its primary applications include cell biology, cancer research, and drug discovery. The compound is not approved for clinical use. It is commercially available from various chemical suppliers for research purposes only. Its mechanism involves inhibition of Arf6 activation and BRAG-mediated nucleotide exchange. |
| Molecular Formula |
C25H17CLN4O3
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|---|---|
| Molecular Weight |
456.880484342575
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| Exact Mass |
456.098
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| Elemental Analysis |
C, 65.72; H, 3.75; Cl, 7.76; N, 12.26; O, 10.51
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| CAS # |
419547-11-8
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| Related CAS # |
419547-11-8;
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| PubChem CID |
2257249
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
5.3
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
33
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| Complexity |
871
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC=C(C=C1)CC2=C(C3=NC(=CC(=O)N3N2)C4=CC=C(C=C4)[N+](=O)[O-])C5=CC=C(C=C5)Cl
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| InChi Key |
WHYGBVWGARJOCS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H17ClN4O3/c26-19-10-6-18(7-11-19)24-22(14-16-4-2-1-3-5-16)28-29-23(31)15-21(27-25(24)29)17-8-12-20(13-9-17)30(32)33/h1-13,15,28H,14H2
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| Chemical Name |
2-benzyl-3-(4-chlorophenyl)-5-(4-nitrophenyl)-1H-pyrazolo[1,5-a]pyrimidin-7-one
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| Synonyms |
Grassofermata; NAV 2729; NAV-2729; NAV2729
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ~50 mg/mL (~109.4 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.08 mg/mL (4.55 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1888 mL | 10.9438 mL | 21.8876 mL | |
| 5 mM | 0.4378 mL | 2.1888 mL | 4.3775 mL | |
| 10 mM | 0.2189 mL | 1.0944 mL | 2.1888 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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