BBT-176
Based on 1 Customer Validation
BBT-176 is an orally active EGFR tyrosine kinase inhibitor. BBT-176 is a reversible ATP-competitive inhibitor with a unique binding mode, and it exhibits selectivity for mutant EGFR over wild-type EGFR. BBT-176 inhibits tumor growth, induces tumor regression, upregulates EGFR expression, and does not trigger secondary EGFR gene mutations. BBT-176 can be used in research related to non-small cell lung cancer.
For research use only. We do not sell to patients.
- Purity: 98.98%
- CAS No.: 2254805-44-0
- Formula: C28H37ClN8O3S
- Molecular Weight:601.16
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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
- Purity & Documentation
- References
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Help & FAQs
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Biological Activity
Description
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| BaF3 | IC50 |
27 nM
Compound: 8; BBT-176
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Inhibition of cell growth in mouse BaF3 cells harboring EGFR del19/T790M/C797S mutant incubated for 72 hrs by fluorescence based assay
Inhibition of cell growth in mouse BaF3 cells harboring EGFR del19/T790M/C797S mutant incubated for 72 hrs by fluorescence based assay
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[PMID: 38908104] |
In Vitro
BBT-176 (0.00001-10 μM; 1 h) is an ATP-competitive, reversible inhibitor that potently inhibits C797S-containing mutant EGFR proteins in biochemical assays, with single-digit nanomolar IC50 values against EGFR19Del/C797S, EGFR19Del/T790M/C797S, and EGFRL858R/C797S at Km ATP[1].
BBT-176 (0.01-10000 nM; 72 h) potently inhibits the growth of Ba/F3 cells expressing C797S-containing mutant EGFR, with greatest activity against 19Del-based mutants (IC50 < 50 nM) and reduced potency against L858R-based mutants and wild-type EGFR cells[1].
BBT-176 (0.01-1000 nM; 72 h)-resistant Ba/F3 clones (derived from EGFR 19Del, 19Del/C797S, and 19Del/T790M/C797S cells) show only 2- to 5-fold higher IC50 values for BBT-176 compared to parental cells, with resistance driven by increased EGFR signaling rather than secondary EGFR mutations[1].
BBT-176 (0.01-1000 nM, 12.35 nM, 13.7 nM; 72 h) combined with Cetuximab (HY-P99050) potently enhances growth inhibition of both parental and BBT-176-resistant EGFR19Del/T790M/C797S-expressing Ba/F3 cells, achieving sub-nanomolar to low-nanomolar IC50 values[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Engineered Ba/F3 cells expressing mutant EGFR (19Del/C797S, 19Del/T790M/C797S, L858R/C797S, L858R/T790M/C797S, wild-type), parental Ba/F3 cells, human NSCLC cell lines with wild-type EGFR (A-431, A549, LoVo, NCI-H1299, NCI-H2073)
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Concentration:0.1-1000 nM
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Incubation Time:72 h
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Result:Inhibited growth of Ba/F3 cells expressing EGFR 19Del/C797S with an IC50 of 42 nM.
Inhibited growth of Ba/F3 cells expressing EGFR 19Del/T790M/C797S with an IC50 of 49 nM.
Inhibited growth of Ba/F3 cells expressing EGFR L858R/C797S with an IC50 of 183 nM.
Inhibited growth of Ba/F3 cells expressing EGFR L858R/T790M/C797S with an IC50 of 202 nM.
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Cell Line:BBT-176-resistant Ba/F3 clones (derived from EGFR 19Del, 19Del/C797S, and 19Del/T790M/C797S-expressing cells via ENU mutagenesis), parental Ba/F3 cells
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Concentration:0.1-1000 nM
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Incubation Time:72 h
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Result:Inhibited growth of EGFR 19Del-resistant clones with IC50 values of 31 nM and 39 nM (parental IC50 = 18 nM).
Inhibited growth of EGFR 19Del/C797S-resistant clones with IC50 values of 109 nM and 113 nM (parental IC50 = 42 nM).
Inhibited growth of EGFR 19Del/T790M/C797S-resistant clones with IC50 values of 240 nM and 242 nM (parental IC50 = 49 nM).
Detected enhanced phosphorylated EGFR levels in EGFR 19Del/T790M/C797S-resistant clones via Western blot analysis.
Detected no secondary EGFR mutations in any resistant clones.
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Cell Line:EGFR 19Del/T790M/C797S-expressing Ba/F3 cells, BBT-176-resistant EGFR 19Del/T790M/C797S Ba/F3 clones
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Concentration:0.1-1000 nM (BBT-176 alone or with 10 μg/mL cetuximab); 12.35 nM, 13.7 nM (fixed BBT-176 with 10 μg/mL cetuximab)
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Incubation Time:72 h
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Result:Reduced IC50 of parental EGFR 19Del/T790M/C797S Ba/F3 cells from 49 nM to 0.63 nM when combined with 10 μg/mL cetuximab, a 78-fold decrease, and showed synergistic growth suppression.
Reduced IC50 values of BBT-176-resistant EGFR 19Del/T790M/C797S clones from 240 nM and 242 nM to 4.5 nM and 4.3 nM, respectively, when combined with 10 μg/mL cetuximab, and showed synergistic growth suppression.
In Vivo
BBT-176 (60-90 mg/kg; p.o.; daily) suppresses tumor growth in a dose-dependent manner in Ba/F3 xenograft models of Osimertinib (HY-15772)-resistant EGFR-mutant non-small cell lung cancer, with complete growth inhibition and 101.3% TGI at 90 mg/kg in the EGFR19Del/C797S model[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 (female, 35-42 days); nu/nu (female, 35-42 days)[1]
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Dosage:60 mg/kg (LU1235 EGFR 19Del PDX model); 90 mg/kg (LD1-0025-200717 EGFR 19Del/T790M/C797S PDX model)
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Administration:p.o.; daily; indicated time period
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Result:Induced complete tumor growth inhibition with 90% tumor growth index (TGI) in the LD1-0025-200717 EGFR 19Del/T790M/C797S PDX model.
Induced tumor regression with only a small decline in body weight in the LU1235 EGFR 19Del PDX model.
Inhibited phosphorylated EGFR (p-EGFR) by 66.5% to 77.5% in tumor samples from mice treated with 90 mg/kg.
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Animal Model:unstated[1]
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Dosage:60 mg/kg; 90 mg/kg
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Administration:p.o.; daily
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Result:Resulted in 64.4% TGI in Ba/F3 EGFR 19Del/C797S xenografts.
Achieved complete tumor growth inhibition with 101.3% TGI in Ba/F3 EGFR 19Del/C797S xenografts at 90 mg/kg.
Resulted in 66% TGI in Ba/F3 EGFR 19Del/T790M/C797S xenografts at 60 mg/kg.
Resulted in 77% TGI in Ba/F3 EGFR 19Del/T790M/C797S xenografts at 90 mg/kg.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 2254805-44-0
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Appearance Solid
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Molecular Weight 601.16
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Formula C28H37ClN8O3S
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Color White to off-white
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SMILES
O=S(NC1=C(NC2=NC(NC3=CC=C(N4CCC(CC4)N5CCN(CC5)C)C=C3OC)=NC=C2Cl)C=CC=C1)(C)=O
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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 : 50 mg/mL (83.17 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)
Purity & Documentation
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Data Sheet (297 KB)
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SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 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 |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.6635 mL | 8.3173 mL | 16.6345 mL | 41.5863 mL |
| 5 mM | 0.3327 mL | 1.6635 mL | 3.3269 mL | 8.3173 mL | |
| 10 mM | 0.1663 mL | 0.8317 mL | 1.6635 mL | 4.1586 mL | |
| 15 mM | 0.1109 mL | 0.5545 mL | 1.1090 mL | 2.7724 mL | |
| 20 mM | 0.0832 mL | 0.4159 mL | 0.8317 mL | 2.0793 mL | |
| 25 mM | 0.0665 mL | 0.3327 mL | 0.6654 mL | 1.6635 mL | |
| 30 mM | 0.0554 mL | 0.2772 mL | 0.5545 mL | 1.3862 mL | |
| 40 mM | 0.0416 mL | 0.2079 mL | 0.4159 mL | 1.0397 mL | |
| 50 mM | 0.0333 mL | 0.1663 mL | 0.3327 mL | 0.8317 mL | |
| 60 mM | 0.0277 mL | 0.1386 mL | 0.2772 mL | 0.6931 mL | |
| 80 mM | 0.0208 mL | 0.1040 mL | 0.2079 mL | 0.5198 mL |
BBT-176 Related Classifications
HY-153974 Related Classifications
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