GNE-371 is a novel, potent and selective chemical probe for the second bromodomains of human transcription-initiation-factor TFIID subunit 1 and transcription-initiation-factor TFIID subunit 1-like with an IC50 of 10 nM for TAF1(2). The biological functions of the dual bromodomains of human transcription-initiation-factor TFIID subunit 1 (TAF1(1,2)) remain unknown, although TAF1 has been identified as a potential target for oncology research. GNE-371 binds TAF1(2) with an IC50 of 10 nM while maintaining excellent selectivity over other bromodomain-family members. GNE-371 is also active in a cellular-TAF1(2) target-engagement assay (IC50 = 38 nM) and exhibits antiproliferative synergy with the BET inhibitor JQ1, suggesting engagement of endogenous TAF1 by GNE-371 and further supporting the use of GNE-371 in mechanistic and target-validation studies.
Physicochemical Properties
| Molecular Formula | C24H25N5O3 |
| Molecular Weight | 431.487004995346 |
| Exact Mass | 431.195 |
| CAS # | 1926986-36-8 |
| PubChem CID | 121335283 |
| Appearance | White to off-white solid powder |
| LogP | 1.5 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 5 |
| Heavy Atom Count | 32 |
| Complexity | 780 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | O1CCN(C(C2=CC3=C(C(=C2)C2=CN(CCC=C)C(C4=C2C=CN4)=O)N=CN3C)=O)CC1 |
| InChi Key | XJRUWGFZGQNPPD-UHFFFAOYSA-N |
| 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 |
| Chemical Name | 6-But-3-enyl-4-[1-methyl-6-(morpholine-4-carbonyl)-benzimidazol-4-yl]-1H-pyrrolo[2,3-c]pyridin-7-one |
| Synonyms | GNE-371; GNE 371; GNE371 |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| 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). |
| References |
[1]. GNE-371, a Potent and Selective Chemical Probe for the Second Bromodomains of Human Transcription-Initiation-Factor TFIID Subunit 1 and Transcription-Initiation-Factor TFIID Subunit 1-like. J Med Chem. 2018 Oct 25;61(20):9301-9315. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~50 mg/mL (~115.88 mM) |
| 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. 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. 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 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 | 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 |