BBT-176 free base · Synonyms: BBT 176 · BBT176

BBT-176 is an orally active EGFR tyrosine kinase inhibitor.

For research use only. Not for human or veterinary use.

Target EGFR Trk Receptor

Research area Cancer

Purity >98% Stock Inquire

Data Sheet SDS COA

BBT-176 structure

CAS No.: 2254805-44-0

Download structure (.mol)

Pack sizes & pricing

Size	Price	SKU	Stock
100 mg	USD 798.00	BP-02281-100mg	In stock	Get quote
250 mg	USD 1,685.00	BP-02281-250mg	In stock	Get quote
500 mg	USD 2,763.00	BP-02281-500mg	In stock	Get quote
1 g	Inquire	BP-02281-1g	In stock	Inquire
2 g	Inquire	BP-02281-2g	In stock	Inquire

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Description

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 .

Biological activity

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. 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. 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. 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. In Vivo BBT-176 (60-90 mg/kg; p.o.; daily; indicated time period) induces potent tumor growth inhibition, complete growth inhibition, or tumor regression in EGFR-mutant non-small cell lung cancer patient-derived xenograft models, with up to 90% TGI and significant suppression of p-EGFR at 90 mg/kg. 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.

Identifiers

SMILES: O=S(=O)(NC=1C=CC=CC1NC2=NC(=NC=C2Cl)NC3=CC=C(C=C3OC)N4CCC(N5CCN(C)CC5)CC4)C
InChIKey: MPISIZFSGAZROV-UHFFFAOYSA-N

Specifications

MW (average): 601.1630
Formula: C₂₈H₃₇ClN₈O₃S
CAS No.: 2254805-44-0
Physical state: Solid
Color: White to off-white
Shipping: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage: Powder -20℃, 3 years; 4℃, 2 years; In solvent -20℃, 1 month;

Solubility

soluble in DMSO

In vitro: DMSO : 50 mg/mL

Documents

References

[1].Lim SM, et al. BBT-176, a Novel Fourth-Generation Tyrosine Kinase Inhibitor for Osimertinib-Resistant EGFR Mutations in Non-Small Cell Lung Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research. 2023 Aug 15;29(16):3004-3016.

Same target

Search EGFR

Same research area

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