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Purity: ≥98%
| Targets |
GW280264X targets ADAM10 and TACE (ADAM17) [1] [2]
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| ln Vitro |
In CX3CL1-expressing ECV-304 cells (CX3CL1-ECV-304), GW280264X effectively inhibits both constitutive and PMA-inducible cleavage of CX3CL1. This leads to reduced release of soluble CX3CL1 and preservation of membrane-bound CX3CL1, thereby maintaining CX3CL1-mediated cell-cell adhesion. It shows broader inhibitory activity compared to ADAM10-preferential inhibitors (e.g., GI254023X) due to its ability to block both ADAM10 and TACE [1]
In human glioma cell line U87 and glioblastoma-initiating cells (GICs), GW280264X inhibits ADAM10 and ADAM17 activity. This inhibition enhances cell-surface expression of ULBP2 (a ligand for natural killer cell receptors) in GICs, promoting immune recognition and targeting of GICs by natural killer cells [2] The co-knockdown therapy of ADAM10/17 or GW280264X resulted in a considerable reduction in GS-7 cell growth [2]. |
| ln Vivo |
Pharmacological inhibition of ADAM10 and ADAM17 improves functional recovery and reduces the number of MHCII+ cells after SCI [3]
Due to the sequence homology between ADAM10 and ADAM17 and their shared substrates (Dreymueller and Ludwig, 2017), we investigated whether ADAM10 and/or ADAM17 can modulate functional and histological recovery after SCI. To do so, we followed an indirect strategy using a specific ADAM10 and a combined ADAM10/ADAM17 pharmacological inhibitor (Hundhausen et al., 2003). C57BL/6 mice were subjected to SCI and were treated either with GW280264x (combined ADAM10/ADAM17 inhibition), GI254023x (specific ADAM10 inhibition), or PBS + DMSO (control) (Fig. 1A). Mice treated with GW280264x showed significantly improved functional recovery compared to the control group (Fig. 1B). In contrast, inhibition of ADAM10 alone had no significant effect on functional recovery compared to control treated mice (Fig. 1B). A trend towards a decreased demyelinated area in GW280264x compared to control mice was observed (Fig. 1C–E), whereas no difference was observed between GI254023x and control treated groups (Fig. 1F). There was no difference in lesion size, astrogliosis and microglia/macrophages (Fig. 1G–I) in GI254023x, GW280264x and control treated mice. However, there was a significant decrease in the number of MHCII+ cells in mice treated with GI254023x and GW280264x compared to controls (Fig. 1J–M). No difference was observed in the number of Arginase-1+ cells or CD4+ T cells in GI254023x or GW280264x compared to control treated mice (Fig. 1N–O). Furthermore, there was no difference in the ratio of 5-HT+ fibers between the 3 groups (Fig. 1P). Taken together, these results indicate that the combined pharmacological inhibition of ADAM10/ADAM17ADAM10/ADAM17 reduces the number of MHCII+ cells and improves functional recovery following SCI suggesting that ADAM17 is responsible for these effects. |
| Enzyme Assay |
For assessing CX3CL1 cleavage inhibition, CX3CL1-ECV-304 cells are treated with GW280264X (with or without PMA stimulation). Soluble CX3CL1 in culture supernatants and membrane-bound CX3CL1 in cell lysates are quantified to determine the extent of cleavage suppression [1]
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| Cell Assay |
Cell Viability Assay[2]
Cell Types: Glioblastoma-initiating cells (GIC) GS-7 cells Tested Concentrations: 0.1, 1, and 3 µM Incubation Duration: 48 hrs (hours) Experimental Results: The proliferation of GIC was inhibited by inhibiting ADAM10 and ADAM17. CX3CL1-ECV-304 cells are seeded and treated with GW280264X for specified durations. Cell-cell adhesion mediated by membrane-bound CX3CL1 is evaluated using adhesion assays, and CX3CL1 isoforms (soluble and membrane-bound) are analyzed via immunodetection methods [1] In glioma models, U87 cells or GICs are seeded, adhered, and treated with GW280264X. Cell-surface ULBP2 expression is measured by flow cytometry or immunofluorescence to assess immune recognition potential [2] |
| Animal Protocol |
Animal/Disease Models: C57BL/6 mice [3]
Doses: 100 μg/kg Route of Administration: intraperitoneal (ip) injection; pharmacological inhibition of ADAM10 and ADAM17 can improve functional recovery after injury (SCI) [3]. Starting 4 hrs (hrs (hours)) after surgery, one time/day for one week. Experimental Results: Compared with the control group, functional recovery was Dramatically improved. Experimental spinal cord injury [3] A T-cut spinal cord hemisection was performed as previously described (Boato et al., 2010, Nelissen et al., 2014, Vidal et al., 2013). Briefly, mice were anesthetized with 3% isoflurane and a partial laminectomy was performed at thoracic level 8 (T8). A complete transection of the dorsomedial and ventral corticospinal tract was induced bilateral dorsal T-cut hemisection using iridectomy scissors. Muscles were sutured and the back skin was closed with wound clips. A glucose solution (20%) was administered i.p. to compensate blood loss during surgery. As post-operative pain treatment, buprenorphine (0.1 mg/kg bodyweight Temgesic) was administrated subcutaneously close to the lesion site. Mice were placed in a recovery chamber (33 °C) post-surgery. Investigators remained blinded to the treatment groups for the duration of the study. Bladders of the mice were emptied daily manually until micturition reflex returned spontaneously. For experiments with pharmacological inhibitors, animals were i.p. injected either with GI254023x (a specific ADAM10 inhibitor; 100 µg/kg), GW280264X (a selective ADAM10/ADAM17 inhibitor; 100 µg/kg) or vehicle (PBS with 0.6% DMSO) every day for one week starting 4 h post-surgery. |
| References |
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| Additional Infomation |
GW280264X is a hydroxamate-based inhibitor with dual specificity for ADAM10 and TACE. Its ability to block both metalloproteinases allows it to regulate processes involving ectodomain shedding, such as chemokine cleavage (CX3CL1) and immune ligand expression (ULBP2), making it relevant for studying cell adhesion and immune modulation in disease models [1] [2]
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| Molecular Formula |
C28H41N5O6S
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|---|---|
| Molecular Weight |
575.725
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| Exact Mass |
575.277
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| Elemental Analysis |
C, 58.41; H, 7.18; N, 12.16; O, 16.67; S, 5.57
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| CAS # |
866924-39-2
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| Related CAS # |
866924-39-2;
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| PubChem CID |
91885425
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| Appearance |
White to off-white solid powder
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| Density |
1.229±0.06 g/cm3
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| LogP |
4.1
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
18
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| Heavy Atom Count |
40
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| Complexity |
782
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| Defined Atom Stereocenter Count |
3
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| SMILES |
CCC[C@@H]([C@@H](CC(C)C)C(=O)N[C@@H](CCCCNC(=O)OCC1=CC=CC=C1)C(=O)NC2=NC=CS2)N(C=O)O
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| InChi Key |
SKJLITFHSZNZMQ-SGNDLWITSA-N
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| InChi Code |
InChI=1S/C28H41N5O6S/c1-4-10-24(33(38)19-34)22(17-20(2)3)25(35)31-23(26(36)32-27-29-15-16-40-27)13-8-9-14-30-28(37)39-18-21-11-6-5-7-12-21/h5-7,11-12,15-16,19-20,22-24,38H,4,8-10,13-14,17-18H2,1-3H3,(H,30,37)(H,31,35)(H,29,32,36)/t22-,23+,24+/m1/s1
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| Chemical Name |
Benzyl N-[(5S)-5-[[(2R,3S)-3-(Formylhydroxyamino)-2-(2-methylpropyl)-1-oxohexyl]amino]-6-oxo-6-(2-thiazolylamino)hexyl]-carbamate
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| Synonyms |
GW280264; GW-280264; GW 280264; GW280264-X; 866924-39-2; benzyl N-[(5S)-5-[[(2R,3S)-3-[formyl(hydroxy)amino]-2-(2-methylpropyl)hexanoyl]amino]-6-oxo-6-(1,3-thiazol-2-ylamino)hexyl]carbamate; CHEMBL5281591; Benzyl ((S)-5-((2R,3S)-3-(N-hydroxyformamido)-2-isobutylhexanamido)-6-oxo-6-(thiazol-2-ylamino)hexyl)carbamate; benzyl N-[(5S)-5-[(2R,3S)-3-(N-hydroxyformamido)-2-(2-methylpropyl)hexanamido]-5-[(1,3-thiazol-2-yl)carbamoyl]pentyl]carbamate; orb1298489; SCHEMBL22889513; GW280264X; GW-280264X; GW 280264X
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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 : ~125 mg/mL (~217.12 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.61 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7369 mL | 8.6846 mL | 17.3693 mL | |
| 5 mM | 0.3474 mL | 1.7369 mL | 3.4739 mL | |
| 10 mM | 0.1737 mL | 0.8685 mL | 1.7369 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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