Physicochemical Properties
| Molecular Formula | C39H48FN9O4 |
| Molecular Weight | 725.854731559753 |
| Exact Mass | 725.381 |
| CAS # | 1799824-08-0 |
| PubChem CID | 91810345 |
| Appearance | White to off-white solid powder |
| LogP | 3.4 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 10 |
| Rotatable Bond Count | 11 |
| Heavy Atom Count | 53 |
| Complexity | 1280 |
| Defined Atom Stereocenter Count | 2 |
| SMILES | N1(CC=C)CC(=O)N2[C@@H](CC3=CC=C(O)C=C3F)C(=O)N(CC3=NC(N4CC(N5CCN(CC)CC5)C4)=CC=C3)C[C@]2([H])N1C(NCC1=CC=CC=C1)=O |
| InChi Key | ZGNKNLOBYFTGRG-GIWKVKTRSA-N |
| InChi Code | InChI=1S/C39H48FN9O4/c1-3-15-47-27-37(51)48-34(20-29-13-14-32(50)21-33(29)40)38(52)46(26-36(48)49(47)39(53)41-22-28-9-6-5-7-10-28)23-30-11-8-12-35(42-30)45-24-31(25-45)44-18-16-43(4-2)17-19-44/h3,5-14,21,31,34,36,50H,1,4,15-20,22-27H2,2H3,(H,41,53)/t34-,36-/m0/s1 |
| Chemical Name | (6S,9aS)-N-benzyl-8-[[6-[3-(4-ethylpiperazin-1-yl)azetidin-1-yl]pyridin-2-yl]methyl]-6-[(2-fluoro-4-hydroxyphenyl)methyl]-4,7-dioxo-2-prop-2-enyl-3,6,9,9a-tetrahydropyrazino[2,1-c][1,2,4]triazine-1-carboxamide |
| 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 Vivo | In a syngeneic mouse model of Wnt1 tumors, E-7386, an oral active modulator of CBP/β-catenin, increases the anti-tumor effectiveness of anti-PD-1 mAb and causes T cell infiltration into tumors. In the Wnt1 model, E-7386 shows strong anti-tumor efficacy. T cell infiltration into the tumor was minimal in the vehicle control group, but it was evident in the E-7386 therapy group [1]. |
| References |
[1]. E7386, an orally active CBP/beta-catenin modulator, induces T cells infiltration into tumor and enhances antitumor activity of anti-PD-1 mAb in Wnt1 tumor syngeneic mice model. Cancer Res 2017;77(13 Suppl):Abstract nr 5172. |
| Additional Infomation | CBP/beta-catenin Modulator E7386 is an orally bioavailable, specific inhibitor of the canonical Wnt/beta-catenin signaling pathway, with potential antineoplastic activity. Upon oral administration, CBP/beta-catenin modulator E7386 inhibits beta-catenin and prevents the interaction of beta-catenin with its transcriptional coactivator, CREB (cAMP response element-binding) binding protein (CBP). This prevents binding of beta-catenin/CBP to WRE (Wnt-responsive element), and inhibits the activation of transcription of a wide range of target genes of Wnt/beta-catenin signaling, thereby preventing gene expression of many Wnt-related, pro-survival proteins and suppressing tumor cell growth. The Wnt/beta-catenin signaling pathway regulates cell morphology, motility, and proliferation; aberrant regulation of this pathway leads to neoplastic proliferation. Beta-catenin is frequently mutated in various tumors. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~125 mg/mL (~172.21 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (2.87 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 20.8 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: ≥ 2.08 mg/mL (2.87 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 20.8 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: ≥ 2.08 mg/mL (2.87 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 20.8 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 | 1.3777 mL | 6.8885 mL | 13.7770 mL | |
| 5 mM | 0.2755 mL | 1.3777 mL | 2.7554 mL | |
| 10 mM | 0.1378 mL | 0.6888 mL | 1.3777 mL |