| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
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| 25mg |
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| 50mg | |||
| 100mg | |||
| 250mg |
Purity: ≥98%
| Targets |
GNE-371 targets the second bromodomain of TAF1 (TAF1(2)) and its paralog TAF1L. TAF1 is a core component of the transcription initiation factor TFIID, which is essential for RNA polymerase II-mediated transcription. TAF1 contains two bromodomains that recognize acetylated lysine residues on histone tails, facilitating the recruitment of TFIID to chromatin and the initiation of transcription. The second bromodomain of TAF1 has been implicated in the regulation of genes involved in cell proliferation, differentiation, and disease. GNE-371 selectively inhibits TAF1(2) with an IC50 of 10 nM, providing a tool to study its specific role in transcription.
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| ln Vitro |
Compound 27, GNE-371, binds TAF1(2) with an IC50 of 10 nM and exhibits good selectivity against other members of the bromodomain family. Additionally, GNE-371 demonstrates antiproliferative synergy with the BET inhibitor JQ1, suggesting that it binds endogenous TAF1. These findings further support the use of GNE-371 in mechanism and target validation investigations, as it is also active in a cellular TAF1(2) target binding test (IC50=38 nM).
In vitro, GNE-371 demonstrates potent inhibition of the TAF1 second bromodomain with an IC50 of 10 nM. Binding assays confirm that GNE-371 selectively displaces acetylated histone peptides from TAF1(2) with high affinity. The compound shows selectivity for TAF1(2) over the first bromodomain of TAF1 and over other bromodomain-containing proteins. In cellular assays, GNE-371 has been used to study the role of TAF1 bromodomains in transcriptional regulation and to identify genes that are dependent on TAF1(2) for their expression. The compound's high potency and selectivity make it a valuable chemical probe for bromodomain biology. |
| ln Vivo |
In vivo activity of GNE-371 has been explored in preclinical models to understand the role of TAF1 bromodomains in disease. As a chemical probe, GNE-371 is used to validate TAF1(2) as a potential therapeutic target. The compound's in vivo effects depend on its pharmacokinetic properties and ability to achieve sufficient target occupancy in tissues. GNE-371 has been studied in the context of cancers and other diseases where TAF1-mediated transcription plays a role. However, detailed in vivo efficacy data are limited in publicly available literature.
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| Enzyme Assay |
In vitro enzyme/receptor binding assays for GNE-371 measure its affinity for the TAF1 second bromodomain using biochemical techniques such as fluorescence polarization (FP), AlphaScreen, or time-resolved fluorescence resonance energy transfer (TR-FRET). These assays use a fluorescently labeled acetylated histone peptide as a tracer, and displacement by GNE-371 is measured to determine IC50 values. Selectivity is assessed by screening GNE-371 against a panel of bromodomain-containing proteins including TAF1(1), BRD2, BRD3, BRD4, BRDT, CBP, and other bromodomains. Surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC) may be used to measure direct binding affinity (Kd).
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| Cell Assay |
In vitro cellular assays for GNE-371 are performed in cell lines to study the role of TAF1 bromodomains in transcription. Cells are treated with GNE-371, and the effects on gene expression are assessed by RNA-seq or qRT-PCR to identify TAF1(2)-dependent genes. Chromatin immunoprecipitation (ChIP) assays using antibodies against TAF1 or acetylated histones can assess the displacement of TAF1 from chromatin. Cell proliferation and viability are measured to evaluate the functional consequences of TAF1(2) inhibition. The compound's cellular activity helps to define the biological functions of TAF1 bromodomains and their potential as therapeutic targets.
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| Animal Protocol |
In vivo animal studies with GNE-371 are conducted in mouse models to validate TAF1(2) as a therapeutic target. Mice receive GNE-371 via oral or intraperitoneal administration, and compound levels in plasma and tissues are measured by LC-MS/MS. Pharmacodynamic endpoints include assessment of target engagement (e.g., by measuring displacement of TAF1 from chromatin) and changes in gene expression in target tissues. Efficacy studies in disease models (e.g., cancer xenografts) evaluate the therapeutic potential of TAF1(2) inhibition. However, detailed in vivo protocols are not extensively reported in public literature for this probe compound.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of GNE-371 have been characterized in preclinical studies to support its use as an in vivo chemical probe. The compound's oral bioavailability, half-life, clearance, and volume of distribution have been determined in rodent models. As a small-molecule bromodomain inhibitor, GNE-371 is expected to exhibit moderate lipophilicity and reasonable cell permeability. Metabolism occurs primarily via hepatic cytochrome P450 enzymes. The compound's PK properties determine the dosing regimen required for achieving therapeutic concentrations in vivo for target engagement and efficacy studies.
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| Toxicity/Toxicokinetics |
Toxicological data for GNE-371 are limited, as it is primarily a chemical probe for research purposes. In preclinical studies, the compound appears to be tolerated at doses used for target engagement and efficacy experiments. However, comprehensive toxicology studies including genotoxicity, safety pharmacology, and repeated-dose toxicity have not been publicly disclosed. As a TAF1 bromodomain inhibitor, potential on-target toxicities could include effects on transcription in normal cells, given the essential role of TAF1 in global transcription initiation. Selectivity for TAF1(2) over other bromodomains may reduce off-target risks.
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| References | |
| Additional Infomation |
GNE-371 is a potent and selective chemical probe for the second bromodomains of human TAF1 and TAF1L, with an IC50 of 10 nM for TAF1(2). It is used to study the role of TAF1 bromodomains in transcriptional regulation and to validate TAF1(2) as a therapeutic target. The compound is a research tool rather than a therapeutic agent, with no clinical development or regulatory approvals reported. Its use is restricted to laboratory research applications.
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| Molecular Formula |
C24H25N5O3
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|---|---|
| Molecular Weight |
431.487004995346
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| Exact Mass |
431.195
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| CAS # |
1926986-36-8
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| PubChem CID |
121335283
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| Appearance |
White to off-white solid powder
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| LogP |
1.5
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
32
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| Complexity |
780
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O1CCN(C(C2=CC3=C(C(=C2)C2=CN(CCC=C)C(C4=C2C=CN4)=O)N=CN3C)=O)CC1
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| InChi Key |
XJRUWGFZGQNPPD-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H25N5O3/c1-3-4-7-29-14-19(17-5-6-25-22(17)24(29)31)18-12-16(13-20-21(18)26-15-27(20)2)23(30)28-8-10-32-11-9-28/h3,5-6,12-15,25H,1,4,7-11H2,2H3
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| Chemical Name |
6-But-3-enyl-4-[1-methyl-6-(morpholine-4-carbonyl)-benzimidazol-4-yl]-1H-pyrrolo[2,3-c]pyridin-7-one
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| Synonyms |
GNE-371; GNE 371; GNE371
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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 Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). 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)
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| Solubility (In Vitro) |
DMSO : ~50 mg/mL (~115.88 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (5.79 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% 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 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.79 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 25.0 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.79 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3176 mL | 11.5878 mL | 23.1755 mL | |
| 5 mM | 0.4635 mL | 2.3176 mL | 4.6351 mL | |
| 10 mM | 0.2318 mL | 1.1588 mL | 2.3176 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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