| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| Other Sizes |
| Targets |
KRAS-SOS1 ( IC50 = 6 nM )
The primary target of BI-3406 is SOS1, a guanine nucleotide exchange factor (GEF) that activates KRAS. By binding to SOS1, BI-3406 blocks its interaction with KRAS, preventing the exchange of GDP for GTP on KRAS. This reduces the levels of GTP-loaded KRAS and inhibits MAPK signaling. It is effective irrespective of the KRAS mutation. |
|---|---|
| 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].
In vitro, BI-3406 is a highly potent and selective SOS1::KRAS inhibitor with an IC50 of 5-6 nM. It selectively binds to SOS1 and blocks its interaction with KRAS. It reduces GTP-loaded KRAS formation and inhibits MAPK signaling. It shows anticancer activity. Its activity makes it a valuable tool for studying KRAS-driven cancers. |
| ln Vivo |
In vivo, BI-3406 acts synergistically with the KRAS inhibitor adagrasib in KRAS G12C mutant lung and colorectal cancer models. It is orally active and has antitumor activity. Its ability to inhibit SOS1::KRAS interaction offers a new approach for treating KRAS-driven tumors. Further studies are needed to fully characterize its in vivo efficacy and safety.
|
| Enzyme Assay |
For SOS1::KRAS interaction assays, the binding between SOS1 and KRAS is measured using techniques like AlphaScreen or surface plasmon resonance. The compounds is incubated with the proteins, and the extent of interaction is measured. IC50 values are calculated. For cellular assays, the effect on downstream signaling (e.g., ERK phosphorylation) and cell proliferation is assessed.
|
| Cell Assay |
For cellular studies, KRAS-mutant cancer cells are cultured in appropriate medium. BI-3406 is dissolved in DMSO and diluted in culture medium. Cells are treated with the compound. Cell viability is assessed by MTT or CellTiter-Glo assays. KRAS-GTP levels are measured by pull-down assays. ERK and AKT phosphorylation are analyzed by Western blot.
|
| Animal Protocol |
For in vivo efficacy studies, immunodeficient mice are implanted with KRAS-mutant cancer cells. BI-3406 is formulated in vehicle and administered orally. Tumor growth is monitored. At study termination, tumors are excised and processed for analysis of KRAS-GTP levels, ERK phosphorylation, and proliferation markers. Pharmacokinetic studies would assess compound levels in plasma and tissues.
|
| ADME/Pharmacokinetics |
Pharmacokinetic data for BI-3406 indicate that it is orally active. It has good oral bioavailability and a favorable PK profile. Its half-life, Cmax, and AUC would be determined in dedicated PK studies. The compound's pharmacokinetic properties support its use in in vivo efficacy studies.
|
| Toxicity/Toxicokinetics |
Toxicological data for BI-3406 are limited, as it is a research compound. In preclinical studies, it has been shown to be well-tolerated at pharmacologically active doses. No acute toxicity, organ-specific toxicity, or mutagenicity data have been reported. As with all research compounds, appropriate safety precautions should be taken during handling.
|
| References | |
| Additional Infomation |
BI-3406 (CAS 2230836-55-0) is a potent, selective, and orally active SOS1::KRAS inhibitor with an IC50 of 5-6 nM. It reduces GTP-loaded KRAS and inhibits MAPK signaling. It acts synergistically with adagrasib. Its molecular formula is C₂₃H₂₅F₃N₄O₃, and its molecular weight is 462.46. It is strictly for research use.
|
| 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)
|
| 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. View More
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. 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) |
| 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 |
*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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
