| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
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| Other Sizes |
| Targets |
BRD4 (BD1) 4.7 nM (IC50) BRD4 (BD2) 4.4 nM (IC50) VHL
GNE-987 targets BRD4 (bromodomain-containing protein 4), a member of the BET (bromodomain and extra-terminal) protein family that regulates gene expression by binding to acetylated histones. It binds to BRD4 bromodomains 1 and 2 (BD1 and BD2) with low nanomolar affinity, exhibiting IC₅₀ values of 4.7 nM and 4.4 nM, respectively. By recruiting the VHL E3 ubiquitin ligase, GNE-987 induces ubiquitination and subsequent proteasomal degradation of BRD4. |
|---|---|
| ln Vitro |
GNE-987 has IC50s of 0.02 and 0.03 nM for EOL-1 and HL-60 cell viability, respectively, and 0.03 nM for MYC expression[1]. GNE-987 breaks down the BRD2 and BRD3 BET family proteins over a 5-hour period (0.1–10 nM)[1].
In vitro, GNE-987 demonstrates picomolar cellular BRD4 degradation activity with a DC₅₀ of 0.03 nM in EOL-1 acute myeloid leukemia (AML) cells. The compound binds to BRD4 BD1 and BD2 with low nanomolar affinity (IC₅₀ of 4.7 nM and 4.4 nM, respectively). This potent degradation activity makes GNE-987 one of the most effective BRD4 degraders reported. The compound is soluble in DMSO at 100 mg/mL. |
| ln Vivo |
In vivo activity data for GNE-987 are limited. As a highly potent BRD4 degrader with picomolar cellular activity, the compound is expected to demonstrate antitumor efficacy in animal models of BRD4-driven cancers, such as acute myeloid leukemia, multiple myeloma, and other BET-dependent malignancies. Typical in vivo studies involve administration to tumor-bearing mouse models to assess tumor growth inhibition and BRD4 degradation in tumors.
|
| Enzyme Assay |
For non-cellular in vitro binding assays, GNE-987 is evaluated for its binding affinity to BRD4 bromodomains 1 and 2. The compound is incubated with purified BRD4 BD1 and BD2 proteins, and binding is measured using techniques such as surface plasmon resonance or fluorescence polarization. The IC₅₀ values for BRD4 BD1 and BD2 are determined from dose-response curves.
|
| Cell Assay |
Western Blot Analysis[1]
Cell Types: EOL-1 cells Tested Concentrations: 0.1, 1, 10 nM Incubation Duration: 5 hrs (hours) Experimental Results: Degraded the BRD2 and BRD3 BET family proteins. For in vitro cellular assays, GNE-987 is tested in BRD4-dependent cancer cell lines such as EOL-1 AML cells. Cells are treated with serial dilutions of the compound, and BRD4 protein levels are measured by Western blot to determine the DC₅₀ for degradation. Cell proliferation and viability are assessed using standard assays. The compound's effects on downstream gene expression are evaluated by qPCR or RNA-seq. |
| Animal Protocol |
For in vivo animal studies, GNE-987 would typically be evaluated in xenograft mouse models of BRD4-driven cancers. Mice bearing established tumors are treated with the compound via intraperitoneal or intravenous administration. Tumor volumes are measured regularly, and BRD4 degradation and target gene expression changes are assessed in tumor tissues at study endpoint. Body weight and general health are monitored to evaluate tolerability.
|
| ADME/Pharmacokinetics |
Pharmacokinetic data for GNE-987 are limited. As a PROTAC with a molecular weight of 1083.23, the compound's pharmacokinetic properties are influenced by its large size and bifunctional nature. The compound is soluble in DMSO at 100 mg/mL and can be formulated for in vivo administration. Information concerning product stability, particularly in solution, has rarely been reported. Further pharmacokinetic studies would be needed to fully characterize its ADME profile.
|
| Toxicity/Toxicokinetics |
Toxicological data for GNE-987 are limited. As a BRD4 degrader that eliminates a key epigenetic regulator, the compound may have on-target effects on normal cellular functions that depend on BRD4. Comprehensive toxicology studies including acute and repeat-dose toxicity, genotoxicity, and organ-specific toxicity assessments would be required for therapeutic development. The compound is for research use only and not for human use.
|
| References | |
| Additional Infomation |
GNE-987 is a highly potent PROTAC degrader of BRD4 with picomolar cellular degradation activity (DC₅₀ of 0.03 nM in EOL-1 cells). It binds to BRD4 BD1 and BD2 with IC₅₀ values of 4.7 nM and 4.4 nM, respectively. The compound consists of a BET inhibitor linked to a VHL E3 ligase ligand via a ten-methylene linker. GNE-987 has a molecular formula of C₅₆H₆₇F₂N₉O₈S₂ and is used in cancer research.
|
| Molecular Formula |
C56H67F2N9O8S2
|
|---|---|
| Molecular Weight |
1096.31
|
| Exact Mass |
1095.452
|
| CAS # |
2417371-71-0
|
| Related CAS # |
(S)-GNE-987;2738533-33-8
|
| PubChem CID |
145925661
|
| Appearance |
White to off-white solid powder
|
| Density |
1.40±0.1 g/cm3(Predicted)
|
| Boiling Point |
1261.9±65.0 °C(Predicted)
|
| LogP |
6.8
|
| Hydrogen Bond Donor Count |
5
|
| Hydrogen Bond Acceptor Count |
14
|
| Rotatable Bond Count |
22
|
| Heavy Atom Count |
77
|
| Complexity |
2210
|
| Defined Atom Stereocenter Count |
3
|
| SMILES |
CC1=C(SC=N1)C2=CC=C(C=C2)CNC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)CCCCCCCCCCNC(=O)C4=CC5=C(C=C4CS(=O)(=O)C)C6=CN(C(=O)C7=C6C(=CN7)CN5C8=C(C=C(C=N8)F)F)C)O
|
| InChi Key |
VTPSYVSGGUUAFN-GDNJTPAESA-N
|
| InChi Code |
InChI=1S/C56H67F2N9O8S2/c1-33-49(76-32-63-33)35-18-16-34(17-19-35)25-62-53(71)45-23-39(68)29-67(45)55(73)50(56(2,3)4)64-46(69)15-13-11-9-7-8-10-12-14-20-59-52(70)40-24-44-41(21-36(40)31-77(6,74)75)42-30-65(5)54(72)48-47(42)37(26-60-48)28-66(44)51-43(58)22-38(57)27-61-51/h16-19,21-22,24,26-27,30,32,39,45,50,60,68H,7-15,20,23,25,28-29,31H2,1-6H3,(H,59,70)(H,62,71)(H,64,69)/t39-,45+,50-/m1/s1
|
| Chemical Name |
8-(3,5-difluoropyridin-2-yl)-N-[11-[[(2S)-1-[(2S,4R)-4-hydroxy-2-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methylcarbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-11-oxoundecyl]-15-methyl-4-(methylsulfonylmethyl)-14-oxo-8,12,15-triazatetracyclo[8.6.1.02,7.013,17]heptadeca-1(16),2(7),3,5,10,13(17)-hexaene-5-carboxamide
|
| 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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO: 150 mg/mL (136.82 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 7.5 mg/mL (6.84 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 75.0 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 | 0.9122 mL | 4.5608 mL | 9.1215 mL | |
| 5 mM | 0.1824 mL | 0.9122 mL | 1.8243 mL | |
| 10 mM | 0.0912 mL | 0.4561 mL | 0.9122 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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