HJB-97 is a novel, potent and high affinity inhibitor of BET bromodomain with Ki values of 0.9 nM (BRD2 BD1), 0.27 nM (BRD2 BD2), 0.18 nM (BRD3 BD1), 0.21 nM (BRD3 BD2), 0.5 nM (BRD4 BD1), 1.0 nM (BRD4 BD2), respectively. It acts by targeting BRD2/3/4 BD1 and BD2. It is used for the design and synthesis of PROTAC-based BET degrader with antitumor activity.
Physicochemical Properties
| Molecular Formula | C26H28N8O3 |
| Molecular Weight | 500.552324295044 |
| Exact Mass | 500.228 |
| CAS # | 2093391-24-1 |
| PubChem CID | 135397673 |
| Appearance | Light yellow to yellow solid powder |
| LogP | 3.9 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 8 |
| Rotatable Bond Count | 7 |
| Heavy Atom Count | 37 |
| Complexity | 832 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | O(C)C1C(C2C(C)=NOC=2C)=CC2=C(C=1)C1C(=NC(C(NC)=O)=NC=1NC1=CC(C3CC3)=NN1CC)N2 |
| InChi Key | JNYHQYRTYFSMSQ-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C26H28N8O3/c1-6-34-20(11-17(32-34)14-7-8-14)29-24-22-15-10-19(36-5)16(21-12(2)33-37-13(21)3)9-18(15)28-23(22)30-25(31-24)26(35)27-4/h9-11,14H,6-8H2,1-5H3,(H,27,35)(H2,28,29,30,31) |
| Chemical Name | 4-((3-Cyclopropyl-1-ethyl-1H-pyrazol-5-yl)amino)-7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-N-methyl-9H-pyrimido[4,5-b]indole-2-carboxamide |
| Synonyms | HJB-97 HJB 97 HJB97 |
| 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 |
| 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 | HJB97 is a highly potent bomer domain and extra terminus (BET) inhibitor, with IC50 values of 3.9 nM (BRD2 BD2), 6.6 nM (BRD3 BD1), 1.9 nM (BRD3 BD2), 7.0 nM (BRD4) BD1), and 7.0 nM (BRD4 BD2)[1]. HJB97 (10-1000 nM, 4 days) efficiently suppresses the development of acute leukemia cell lines MOLM-13 and RS4;11, with corresponding IC50 values of 25.6 nM and 24.1 nM [1]. At a dose of 300–1000 nM, HJB97 can successfully downregulate the levels of c-Myc in the RS4;11 cell line after a 24-hour treatment [1]. |
| Cell Assay |
Cell viability assay [1] Cell Types: human acute leukemia RS4;11 cell line; human acute leukemia MOLM-13 cell line Tested Concentrations: 10-1000 nM Incubation Duration: 4 days Experimental Results: Inhibition of RS4;11 cell and MOLM-13 cell growth The IC50 values are 24.1±5.3 nM and 25.6±1.9 nM respectively. Western Blot Analysis[1] Cell Types: RS4; 11 cells Tested Concentrations: 30, 100, 300, 1000 nM Incubation Duration: 24 hrs (hours) Experimental Results: c-Myc levels are downregulated in RS4, but at concentrations of 300-1000 nM; 11 cell line . |
| References |
[1]. Discovery of a Small-Molecule Degrader of Bromodomain and Extra-Terminal (BET) Proteins with Picomolar Cellular Potencies and Capable of Achieving Tumor Regression. J Med Chem. 2018 Jan 25;61(2):462-481. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~30 mg/mL (~59.93 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.99 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% 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 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 (4.99 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 | 1.9978 mL | 9.9890 mL | 19.9780 mL | |
| 5 mM | 0.3996 mL | 1.9978 mL | 3.9956 mL | |
| 10 mM | 0.1998 mL | 0.9989 mL | 1.9978 mL |