BI-3406

Catalog No.S8916 Batch:S891601

Technical Data

Formula	C₂₃H₂₅F₃N₄O₃
Molecular Weight	462.46	CAS No.	2230836-55-0
Solubility (25°C)*	In vitro	DMSO	92 mg/mL (198.93 mM)
		Ethanol	92 mg/mL (198.93 mM)
		Water	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description

BI-3406 (compound I-13) is a potent, selective and orally active inhibitor of the interaction between KRAS and Son of Sevenless 1 (SOS1) with IC50 of 5 nM. BI-3406 reduces the formation of GTP-loaded KRAS, and inhibits MAPK pathway signaling. BI-3406 exhibits anti-tumor activities.

Targets

K-ras ^[1]
(Cell-free assay)

5 nM

Biological Activity

Description

Targets

K-ras ^[1]
(Cell-free assay)

5 nM

In vitro

BI-3406, a selective SOS1 inhibitor, enhanced the AMG 510-induced growth suppression in MIA PaCa-2 cells. Treatment with 5 µM BI-3406 following the excision of endogenous mutant KRAS abolishes both ERK and AKT activation, consistent with the inhibition of WT RAS signaling.^[1]

In vivo

BI-3406, a potent and selective SOS1-KRAS Interaction Inhibitor, is effective in KRAS-driven cancers through combined MEK inhibition.^[2]

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines MIA PaCa-2, mT42 cells Concentrations 5 μM, 20 μM to 2 nM Incubation Time 4 days Method MIA PaCa-2 cells were seeded at 2,000 cells per well and treated 24 h after seeding with 5 μM BI-3406 or DMSO control and AMG 510 (from 5 μM to 0.1 nM). Cell viability was measured after 4 d with CellTiter-Glo. mT42 cells were seeded at 1,000 cells per well and treated with 4-OHT or DMSO control and BI-3406 in a dose–response manner (from 20 μM to 2 nM). Cell viability was measured using CellTiter-Glo Luminescence assay at day 4. FPC cell line mT42 cells were treated with 5 μM BI-3406, 20 nM trametinib, or DMSO vehicle control in the presence or absence of mutant KRAS by treatment with DMSO vehicle control or 4-OHT, respectively. Immunoblotting was performed for RAS pathways by phospho-ERK and phospho-AKT and the RSK1 substrate phospho-S6.
Animal Study:^{^[2]}	Animal Models NSG female mice of KRAS G12V and KRAS Q61K mutant pancreatic PDX model Dosages 50 mg/kg Administration p.o.

Cell Assay:^{^[1]}

Cell lines
MIA PaCa-2, mT42 cells
Concentrations
5 μM, 20 μM to 2 nM
Incubation Time
4 days
Method
MIA PaCa-2 cells were seeded at 2,000 cells per well and treated 24 h after seeding with 5 μM BI-3406 or DMSO control and AMG 510 (from 5 μM to 0.1 nM). Cell viability was measured after 4 d with CellTiter-Glo. mT42 cells were seeded at 1,000 cells per well and treated with 4-OHT or DMSO control and BI-3406 in a dose–response manner (from 20 μM to 2 nM). Cell viability was measured using CellTiter-Glo Luminescence assay at day 4. FPC cell line mT42 cells were treated with 5 μM BI-3406, 20 nM trametinib, or DMSO vehicle control in the presence or absence of mutant KRAS by treatment with DMSO vehicle control or 4-OHT, respectively. Immunoblotting was performed for RAS pathways by phospho-ERK and phospho-AKT and the RSK1 substrate phospho-S6.

Animal Study:^{^[2]}

Animal Models
NSG female mice of KRAS G12V and KRAS Q61K mutant pancreatic PDX model
Dosages
50 mg/kg
Administration
p.o.

References

Selleck's BI-3406 has been cited by 5 publications

RAS-dependent RAF-MAPK hyperactivation by pathogenic RIT1 is a therapeutic target in Noonan syndrome-associated cardiac hypertrophy [ Sci Adv, 2023, 9(28):eadf4766]	PubMed: 37450595
RAS-dependent RAF-MAPK hyperactivation by pathogenic RIT1 is a therapeutic target in Noonan syndrome-associated cardiac hypertrophy [ Sci Adv, 2023, 9(28):eadf4766]	PubMed: 37450595
Impaired proteolysis of non-canonical RAS proteins drives clonal hematopoietic transformation [ Cancer Discov, 2022, CD-21-1631]	PubMed: 35904492
In vivo genome-wide CRISPR screening identifies ZNF24 as a negative NF-κB modulator in lung cancer [ Cell Biosci, 2022, 12(1):193]	PubMed: 36457047
Profiling oncogenic KRAS mutant drugs with a cell-based Lumit p-ERK immunoassay [ SLAS Discov, 2022, S2472-5552(22)12517-7]	PubMed: 35288294

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SHIPPING AND STORAGE
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