| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
VZ185 targets BRD7 and BRD9, which are bromodomain-containing proteins involved in chromatin remodeling and gene transcription. It is a PROTAC that recruits the VHL E3 ligase to induce degradation of BRD7 and BRD9. It has DC₅₀ values of 4.5 nM for BRD7 and 1.8 nM for BRD9.
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| ln Vitro |
VZ185's efficacy was validated by degradation study in a collection of other human tumor lines (EOL-1, A-204) (DC50 topic for BRD9 between 2 and 8 nM). The remarkable hydrodynamic solubility (up to about 100 μM) and stability of VZ185 in these solutions and microsomes are further supported by external PK data [1].
In vitro, VZ185 potently induces degradation of BRD7 and BRD9 with DC₅₀ values of 4.5 and 1.8 nM, respectively. It shows selectivity for BRD7/9 degradation over other bromodomain-containing proteins and other BAF/PBAF subunits. It is a fast degrader. |
| ln Vivo |
In vivo, VZ185 has been studied for its potential in treating cancers driven by BRD7/9. By degrading BRD7 and BRD9, it disrupts chromatin remodeling and inhibits tumor cell growth. It has been used as a tool to study the role of BRD7/9 in cancer biology.
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| Enzyme Assay |
The in vitro degradation assay for VZ185 involves treating cells with the compound and measuring BRD7 and BRD9 protein levels by Western blotting. The concentration required for 50% degradation (DC₅₀) is determined. The kinetics of degradation are also assessed.
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| Cell Assay |
In vitro cell-based assays for VZ185 are performed using cancer cell lines that express BRD7 and BRD9. Cells are treated with VZ185, and cell proliferation is measured. The effects on gene expression are analyzed by RNA-seq. The compound's selectivity for BRD7/9 over other bromodomain proteins is confirmed.
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| Animal Protocol |
In vivo animal experiments for VZ185 have been conducted in xenograft models of cancers driven by BRD7/9. Animals are administered the compound via appropriate routes, and tumor growth inhibition is measured. BRD7 and BRD9 degradation in tumor tissues is confirmed by Western blotting.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of VZ185 have been characterized in preclinical species. It achieves sufficient plasma concentrations to exert its pharmacological effects. Detailed PK parameters such as half-life, clearance, and bioavailability are determined from plasma concentration-time profiles.
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| Toxicity/Toxicokinetics |
Toxicological data for VZ185 are limited. In standard preclinical safety assessments, it would be evaluated for potential off-target effects and general toxicity. The compound is intended for research use only and not for therapeutic use in humans.
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| References | |
| Additional Infomation |
VZ185 is a potent and selective dual BRD7/9 degrader that has been used as a tool to study the role of these bromodomain proteins in cancer. It is a VHL-based PROTAC. It has not been approved for clinical use.
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| Molecular Formula |
C53H67FN8O8S
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|---|---|
| Molecular Weight |
995.211295366287
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| Exact Mass |
994.478
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| CAS # |
2306193-61-1
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| PubChem CID |
138454768
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| Appearance |
White to off-white solid powder
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| LogP |
5.1
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
14
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| Rotatable Bond Count |
20
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| Heavy Atom Count |
71
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| Complexity |
1850
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| Defined Atom Stereocenter Count |
3
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| SMILES |
S1C=NC(C)=C1C1=CC=C(C(=C1)OCCCCCN1CCN(CC2C(=CC(C3=CN(C)C(C4C=NC=CC3=4)=O)=CC=2OC)OC)CC1)CNC([C@@H]1C[C@H](CN1C([C@H](C(C)(C)C)NC(C1(CC1)F)=O)=O)O)=O
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| InChi Key |
ZAGCLFXBHOXXEN-JPTLTNPLSA-N
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| InChi Code |
InChI=1S/C53H67FN8O8S/c1-33-46(71-32-57-33)34-11-12-35(27-56-48(64)42-26-37(63)29-62(42)50(66)47(52(2,3)4)58-51(67)53(54)14-15-53)43(23-34)70-22-10-8-9-17-60-18-20-61(21-19-60)31-41-44(68-6)24-36(25-45(41)69-7)40-30-59(5)49(65)39-28-55-16-13-38(39)40/h11-13,16,23-25,28,30,32,37,42,47,63H,8-10,14-15,17-22,26-27,29,31H2,1-7H3,(H,56,64)(H,58,67)/t37-,42+,47-/m1/s1
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| Chemical Name |
(2S,4R)-N-[[2-[5-[4-[[2,6-dimethoxy-4-(2-methyl-1-oxo-2,7-naphthyridin-4-yl)phenyl]methyl]piperazin-1-yl]pentoxy]-4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-1-[(2S)-2-[(1-fluorocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-4-hydroxypyrrolidine-2-carboxamide
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| Synonyms |
VZ-185; VZ185; VZ 185
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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 : ~200 mg/mL (~200.96 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (5.02 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 50.0 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 | 1.0048 mL | 5.0241 mL | 10.0481 mL | |
| 5 mM | 0.2010 mL | 1.0048 mL | 2.0096 mL | |
| 10 mM | 0.1005 mL | 0.5024 mL | 1.0048 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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