SB590885

Catalog No.S2220 Batch:S222007

Technical Data

Formula

C₂₇H₂₇N₅O₂

Molecular Weight

453.54

CAS No.

405554-55-4

Solubility (25°C)*

In vitro

DMSO

23 mg/mL (50.71 mM)

Water

Insoluble

Ethanol

Insoluble

In vivo (Add solvents to the product individually and in order)

Clear solution

2% Cremophor EL 1 2% N 2 N-dimethylacetamide 3 pH 5.0

30.0mg/ml

* <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

SB590885 is a potent B-Raf inhibitor with K_i of 0.16 nM in a cell-free assay, 11-fold greater selectivity for B-Raf over c-Raf, no inhibition to other human kinases.

Targets

B-Raf ^[1]
(Cell-free assay)

0.16 nM(Ki)

In vitro

SB590885 displays significant selectivity for B-Raf over c-Raf with K_i of 0.16 nM over 1.72 nM. SB-590885 is a more potent inhibitor than the previously described Raf/VEGFR kinase inhibitor BAY 439006 (K_i = 38 nM for mutant B-Raf, 6 nM for c-Raf). SB590885 displays potent selectivity over 46 other kinases. Unlike the multi-kinase inhibitor BAY43-9006, SB590885 stabilizes the oncogenic B-Raf kinase domain in an active configuration. In Colo205, HT29, A375P, SKMEL28, and MALME-3M cells expressing oncogenic B-RafV600E, SB590885 treatment potently inhibits ERK phosphorylation with EC50 of 28 nM, 58 nM, 290 nM, 58 nM, and 190 nM, respectively, and consistently, inhibits the proliferation with EC50 of 0.1 μM, 0.87 μM, 0.37 μM, 0.12 μM, and 0.15 μM, respectively. SB590885 decreases anchorage-independent growth of melanoma cell lines in a BRAF mutant-selective manner. ^[1] SB590885 displays high affinity for B-Raf with Kd of 0.3 nM. ^[2] Most of the melanoma cell lines that harbor the BRAF V600E mutation and lack CDK4 mutations (451Lu, WM35, and WM983) are highly sensitive to SB590885 with IC50 of <1 μM. Increased levels of cyclin D1 resulting from genomic amplification mediate SB590885 resistance in B-Raf V600E-mutated melanomas. ^[3]

In vivo

Administration of SB590885 potently decreases tumorigenesis in murine xenografts established from mutant B-Raf-expressing A375P melanoma cells, and modestly inhibits tumor growth. ^[1]

Features

Displays significant selectivity for B-Raf over c-Raf.

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines Colo205, HT29, A375P, SKMEL28, and MALME-3M Concentrations Dissolved in DMSO, final concentrations ~10 μM Incubation Time 72 hours Method Cells are treated with increasing concentrations of SB590885 and incubated for 72 hours. Viable cells are quantified using CellTiter-Glo reagent and luminescence detection on a Victor 2V plate reader. Cells are prepared for cell cycle analysis on a Becton Dickinson FACScan. Data is acquired and analyzed using CellQuest v3.3 software.
Animal Study:^{^[1]}	Animal Models Female nude mice injected s.c. with of A375P cells Dosages 50 mg/kg/day Administration Injection i.p.

Cell Assay:^{^[1]}

Cell lines
Colo205, HT29, A375P, SKMEL28, and MALME-3M
Concentrations
Dissolved in DMSO, final concentrations ~10 μM
Incubation Time
72 hours
Method
Cells are treated with increasing concentrations of SB590885 and incubated for 72 hours. Viable cells are quantified using CellTiter-Glo reagent and luminescence detection on a Victor 2V plate reader. Cells are prepared for cell cycle analysis on a Becton Dickinson FACScan. Data is acquired and analyzed using CellQuest v3.3 software.

Animal Study:^{^[1]}

Animal Models
Female nude mice injected s.c. with of A375P cells
Dosages
50 mg/kg/day
Administration
Injection i.p.

References

Customer Product Validation

: Data from [Invest New Drugs, 2014, 32(4), 626-35]

: Data from [Data independently produced by , , Oncotarget, 2015, 6(17):15250-64.]

: Data from [Data independently produced by , , Chembiochem, 2018, doi:10.1002/cbic.201800359]

Selleck's SB590885 has been cited by 40 publications

Self-renewing human naïve pluripotent stem cells dedifferentiate in 3D culture and form blastoids spontaneously [ Nat Commun, 2024, 15(1):668]	PubMed: 38253551
A transient transcriptional activation governs unpolarized-to-polarized morphogenesis during embryo implantation [ Mol Cell, 2024, 84(14):2665-2681.e13]	PubMed: 38955180
Integrated drug response prediction models pinpoint repurposed drugs with effectiveness against rhabdomyosarcoma [ PLoS One, 2024, 19(1):e0295629]	PubMed: 38277404
Generation of a humanized mesonephros in pigs from induced pluripotent stem cells via embryo complementation [ Cell Stem Cell, 2023, 30(9):1235-1245.e6]	PubMed: 37683604
Modeling human pregastrulation development by 3D culture of blastoids generated from primed-to-naïve transitioning intermediates [ Protein Cell, 2023, 14(5):337-349]	PubMed: 37155315
Short C-terminal Musashi-1 proteins regulate pluripotency states in embryonic stem cells [ Cell Rep, 2023, 42(10):113308]	PubMed: 37858462
Chemical-induced epigenome resetting for regeneration program activation in human cells [ Cell Rep, 2023, 42(6):112547]	PubMed: 37224020
Discordance between chromatin accessibility and transcriptional activity during the human primed-to-naïve pluripotency transition process [ Cell Regen, 2023, 10.1186/s13619-023-00179-2]	PubMed: 37938437
Cell fate roadmap of human primed-to-naive transition reveals preimplantation cell lineage signatures [ Nat Commun, 2022, 13(1):3147]	PubMed: 35672317
Comprehensive Molecular Analysis Identified an SRSF Family-Based Score for Prognosis and Therapy Efficiency Prediction in Hepatocellular Carcinoma [ Cancers (Basel), 2022, 14(19)4727]	PubMed: 36230650

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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