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BI-3406 (BI3406; SOS1-IN-2) is a novel, orally bioactive, and selective inhibitor of Son of Sevenless 1 (SOS1) with anticancer activity. It selectively binds to SOS1 and blocks KRAS and SOS1 interaction with an IC50 of 6 nM. BI-3406 is capable of lowering the production of GTP-bound KRAS, which blocks the signaling of the MAPK pathway.
Physicochemical Properties
| Molecular Formula | C23H25F3N4O3 |
| Molecular Weight | 462.4648 |
| Exact Mass | 462.19 |
| Elemental Analysis | C, 59.73; H, 5.45; F, 12.32; N, 12.11; O, 10.38 |
| CAS # | 2230836-55-0 |
| PubChem CID | 138911318 |
| Appearance | White to off-white solid powder |
| LogP | 4.3 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 10 |
| Rotatable Bond Count | 6 |
| Heavy Atom Count | 33 |
| Complexity | 643 |
| Defined Atom Stereocenter Count | 2 |
| SMILES | CC1=NC2=CC(=C(C=C2C(=N1)N[C@H](C)C3=CC(=CC(=C3)N)C(F)(F)F)O[C@H]4CCOC4)OC |
| InChi Key | XVFDNRYZXDHTHT-PXAZEXFGSA-N |
| InChi Code | InChI=1S/C23H25F3N4O3/c1-12(14-6-15(23(24,25)26)8-16(27)7-14)28-22-18-9-21(33-17-4-5-32-11-17)20(31-3)10-19(18)29-13(2)30-22/h6-10,12,17H,4-5,11,27H2,1-3H3,(H,28,29,30)/t12-,17+/m1/s1 |
| Chemical Name | N-[(1R)-1-[3-amino-5-(trifluoromethyl)phenyl]ethyl]-7-methoxy-2-methyl-6-[(3S)-oxolan-3-yl]oxyquinazolin-4-amine |
| Synonyms | BI3406; BI-3406; BI 3406; SOS1-IN2BI-3406; SOS1-IN-2BI 3406 |
| 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: 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
| Targets | KRAS-SOS1 ( IC50 = 6 nM ) |
| ln Vitro | BI-3406 is a response between KRAS and the guanine-binding factor (GEF) SOS1. BI-3406 does not elicit KRAS and SOS2 responses, but does elicit activity on a broad range of KRAS food variants, including all major G12 and G13 oncoproteins. In KRAS G12 or G13 mutant cells, dehydration of this signaling cascade by BI-3406 effectively limits cell proliferation [2]. |
| References |
[1]. Novel benzylamino substituted quinazolines and derivatives as sos1 inhibitors. WO2018115380A1. [2]. Abstract PL06-01: Discovery of BI-3406: A potent and selective SOS1::KRAS inhibitor opens a new approach for treating KRAS-driven tumors. December 2019. |
Solubility Data
| Solubility (In Vitro) |
Ethanol: ~100 mg/mL (~216.2 mM) DMSO: 92~100 mg/mL (198.9~216.2 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.41 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 (5.41 mM) 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; with ultrasonication. 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 (5.41 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. Solubility in Formulation 4: ≥ 2.5 mg/mL (5.41 mM) (saturation unknown) in 10% EtOH + 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 EtOH stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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 5: ≥ 2.5 mg/mL (5.41 mM) (saturation unknown) in 10% EtOH + 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 EtOH 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 6: ≥ 2.5 mg/mL (5.41 mM) (saturation unknown) in 10% EtOH + 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 EtOH stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 7: 5%DMSO + Corn oil: 5.0mg/ml (10.81mM) (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1623 mL | 10.8117 mL | 21.6235 mL | |
| 5 mM | 0.4325 mL | 2.1623 mL | 4.3247 mL | |
| 10 mM | 0.2162 mL | 1.0812 mL | 2.1623 mL |