BTX-6654 formate
Based on 1 Customer Validation
BTX-6654 formate is a SOS1 PROTAC degrader. BTX-6654 formate induces ubiquitination and degradation of SOS1 via the proteasomal pathway by bridging SOS1 with the E3 ligase CRBN to form a ternary complex, thereby blocking KRAS activation and downregulating the MAPK signaling pathway (pERK/pS6), and ultimately inhibiting tumor growth. BTX-6654 formate can be used in research on various cancers driven by KRAS mutations.
(Pink: SOS1 ligand (HY-175896); Blue: Cereblon ligand (HY-138881); Black: linker).
For research use only. We do not sell to patients.
- Purity : 98.85%
- Formula: C51H59F4N9O7
- Molecular Weight:986.06
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Protocols
- Purity & Documentation
- References
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Help & FAQs
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Biological Activity
Description
In Vitro
BTX-6654 (0.1 nM-10 µM; 24 h) formate induces significant, target-dependent and specific SOS1 degradation in MIA PaCa-2 and LoVo cells[1].
BTX-6654 (200 nM; eluted for 24 h after 24 h of treatment) formate sustains persistent degradation of SOS1 in MIA PaCa-2 and LoVo cells[1].
BTX-6654 (50-200 nM; 1-6 h) formate exhibits time-dependent and selective SOS1 degradation activity in MIA PaCa-2 and LoVo cells[1].
BTX-6654 (50-200 nM; 6 h) formate exhibits rescued SOS1 degradation when combined with CC-220 (HY-101291) (10 µM) in MIA PaCa-2 and LoVo cells, and shows blocked SOS1 degradation when combined with MG132 (HY-13259) (10 µM) or MLN4924 (HY-70062) (1 µM) in MIA PaCa-2 and LoVo cells[1].
BTX-6654 (50-200 nM; 6 h) formate induces degradation of wild-type SOS1 in H358 transgenic cells expressing FLAG-SOS1 WT, but exhibits no degradation activity in cells expressing the H905V or N879A/H905V mutants[1].
BTX-6654 (0.8-500 nM; 24 h) formate reduces the activity of downstream pERK, pS6 and pAKT signaling in MIA PaCa-2 cells, and inhibits pERK and pS6 phosphorylation in LoVo and A549 cells[1].
BTX-6654 (100-500 nM; 6 h) formate combines with CC-220 (10 µM) results in the rescue of pERK and pS6 inhibition in LoVo cells.[1].
BTX-6654 (0.01 pM-100 µM; 5-6 days in 3D culture or 3 days in 2D culture) formate significantly inhibites cell proliferation in EBC-1, NCI-H358, and MIA PaCa-2 cells, with IC50 values of 17.8 nM, 1.12 nM, and 7.5 nM, respectively, while exhibiting extremely low cytotoxicity in normal HEK293 and NHLF cell lines[1].
BTX-6654 (0.01 pM-10 µM; 5-6 days) formate does not reduce cell viability in MIA PaCa-2 (SOS1 KO) cells, indicating that its proliferation inhibitory activity is SOS1-dependent[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MIA PaCa-2, LoVo
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Concentration:50, 200 nM
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Incubation Time:1, 2, 4, 6 h
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Result:Resulted in time-dependent, maximal degradation of SOS1 within 6 hours.
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Cell Line:MIA PaCa-2, LoVo
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Concentration:50, 200 nmol/L (+ CC-220, MG132 or MLN4924)
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Incubation Time:6 h
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Result:Induced degradation of SOS1 was completely blocked by the CRBN ligand or proteasome/NEDD8 inhibitors.
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Cell Line:MIA PaCa-2 (3D)
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Concentration:0.8, 4, 20, 100, 500 nM
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Incubation Time:24 h
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Result:Significantly inhibited the downstream phosphorylation of pERK and pS6.
In Vivo
BTX-6654 (2-10 mg/kg; i.p.; twice daily; 28 days) formate exhibits significant, dose-dependent tumor growth inhibition in NCI-H358 and MIA PaCa-2 xenograft models[1].
BTX-6654 (10 mg/kg; i.p.; twice daily; 30 days) formate in combination with Sotorasib (HY-114277) (10 mg/kg; p.o.; once daily) or Trametinib ( HY-10999) (0.125 mg/kg; p.o.; twice daily) demonstrates significant synergistic tumor growth inhibition in MIA PaCa-2 xenograft models[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c nude mice (6-8 weeks old, female) were subcutaneously inoculated with NCI-H358 cells in the right flank[1]
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Dosage:10, 50 mg/kg
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Administration:i.p.; single dose; 2, 8, 24 h
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Result:Downregulated SOS1 and pERK proteins in histology.
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Animal Model:BALB/c nude mice (6-8 weeks old, female) were subcutaneously inoculated with NCI-H358 cells or MIA PaCa-2 cells in the right flank[1]
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Dosage:2, 10 mg/kg
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Administration:i.p.; twice daily; 28 days
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Result:Inhibited tumor growth in a dose-dependent manner.
No significant effect on animal body weight.
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Animal Model:BALB/c nude mice (6-8 weeks old, female) were subcutaneously inoculated with xMIA PaCa-2 cells in the right flank[1]
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Dosage:10 mg/kg (+ 10 mg/kg Sotorasib or 0.125 mg/kg Trametinib)
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Administration:i.p.; twice daily; 30 days
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Result:A trend toward profound tumor regression was observed in the combination therapy group.
Chemical Information
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Appearance Solid
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Molecular Weight 986.06
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Formula C51H59F4N9O7
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Color White to off-white
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SMILES
FC(F)(F)C1=C(C)C([C@@H](C)NC2=NN=C(C)C3=CC=C(N4CCN(C(C5CCN(C(CCN6CCC(C7=CC(CN(C8CCC(NC8=O)=O)C9=O)=C9C=C7F)CC6)=O)CC5)=O)CC4)C=C32)=CC=C1.O=CO
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvent & Solubility
In Vitro:
DMSO : 100 mg/mL (101.41 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (2.54 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (2.54 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation
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Data Sheet (281 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2659 KB)
References
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
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| DMSO | 1 mM | 1.0141 mL | 5.0707 mL | 10.1414 mL | 25.3534 mL |
| 5 mM | 0.2028 mL | 1.0141 mL | 2.0283 mL | 5.0707 mL | |
| 10 mM | 0.1014 mL | 0.5071 mL | 1.0141 mL | 2.5353 mL | |
| 15 mM | 0.0676 mL | 0.3380 mL | 0.6761 mL | 1.6902 mL | |
| 20 mM | 0.0507 mL | 0.2535 mL | 0.5071 mL | 1.2677 mL | |
| 25 mM | 0.0406 mL | 0.2028 mL | 0.4057 mL | 1.0141 mL | |
| 30 mM | 0.0338 mL | 0.1690 mL | 0.3380 mL | 0.8451 mL | |
| 40 mM | 0.0254 mL | 0.1268 mL | 0.2535 mL | 0.6338 mL | |
| 50 mM | 0.0203 mL | 0.1014 mL | 0.2028 mL | 0.5071 mL | |
| 60 mM | 0.0169 mL | 0.0845 mL | 0.1690 mL | 0.4226 mL | |
| 80 mM | 0.0127 mL | 0.0634 mL | 0.1268 mL | 0.3169 mL | |
| 100 mM | 0.0101 mL | 0.0507 mL | 0.1014 mL | 0.2535 mL |
BTX-6654 formate Related Classifications
HY-161233A Related Classifications
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