SB-590885

Name: SB-590885
Brand: MedChemExpress
SKU: HY-10966
Rating: 5.0 (5 reviews)

Cat. No.: HY-10966 Purity: 99.77%: FAQs
Data Sheet SDS COA Handling Instructions

Molarity Calculator

SB-590885 is a potent?B-Raf?inhibitor with?K_i?of 0.16 nM, and has 11-fold greater selectivity for B-Raf over c-Raf, without inhibition to other human kinases.

For research use only. We do not sell to patients.

SB-590885 Chemical Structure

CAS No. : 405554-55-4

Size	Price	Stock	Quantity

Free Sample (0.1 - 0.5 mg)		Apply Now
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO ready for reconstitution	USD 182	In-stock	Estimated Time of Arrival: December 31
Solution
10 mM * 1 mL in DMSO	USD 182	In-stock	Estimated Time of Arrival: December 31
Solid
5 mg	USD 106	In-stock	Estimated Time of Arrival: December 31
10 mg	USD 165	In-stock	Estimated Time of Arrival: December 31
50 mg	USD 620	In-stock	Estimated Time of Arrival: December 31
100 mg	USD 960	In-stock	Estimated Time of Arrival: December 31
200 mg		Get quote
500 mg		Get quote

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Customer Review

Based on 5 publication(s) in Google Scholar

5 Publications Citing Use of MCE SB-590885

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BRaf c-Raf Raf

Biological Activity
Protocol
Purity & Documentation
References
Customer Review

Description

SB-590885 is a potent?B-Raf?inhibitor with?K_i?of 0.16 nM, and has 11-fold greater selectivity for B-Raf over c-Raf, without inhibition to other human kinases.

IC₅₀ & Target^[1]

B-Raf

0.16 nM (Ki)

c-Raf

1.72 nM (Ki)

Cellular Effect

Cell Line	Type	Value	Description	References
A-375	IC₅₀	370 nM Compound: 2; SB-590885	Cytotoxicity against human A375 cells harboring BRAF V600E mutant after 48 hrs by CellTiter-Glo assay Cytotoxicity against human A375 cells harboring BRAF V600E mutant after 48 hrs by CellTiter-Glo assay	[PMID: 29461827]
A549	EC₅₀	0.028 μM Compound: 6, SB-590885	Inhibition of B-Raf V600E mutant-mediated Erk phosphorylation in human A549 cells after 60 mins by Western blot analysis Inhibition of B-Raf V600E mutant-mediated Erk phosphorylation in human A549 cells after 60 mins by Western blot analysis	[PMID: 22222036]
COLO 205	EC₅₀	0.028 μM Compound: 6, SB-590885	Inhibition of B-Raf V600E mutant-mediated Erk phosphorylation in human Colo205 cells after 60 mins by Western blot analysis Inhibition of B-Raf V600E mutant-mediated Erk phosphorylation in human Colo205 cells after 60 mins by Western blot analysis	[PMID: 22222036]
HCT-116	EC₅₀	1.1 μM Compound: 6, SB-590885	Growth inhibition of human HCT116 cells expressing wild-type B-Raf and K-Ras2 G13D mutant after 72 hrs by WST-1 assay Growth inhibition of human HCT116 cells expressing wild-type B-Raf and K-Ras2 G13D mutant after 72 hrs by WST-1 assay	[PMID: 22222036]
HFF	EC₅₀	1.1 μM Compound: 6, SB-590885	Inhibition of B-Raf-mediated Erk phosphorylation in human HFF cells after 60 mins by Western blot analysis Inhibition of B-Raf-mediated Erk phosphorylation in human HFF cells after 60 mins by Western blot analysis	[PMID: 22222036]
HMEC	EC₅₀	1.1 μM Compound: 6, SB-590885	Inhibition of B-Raf-mediated Erk phosphorylation in human HMEC cells after 60 mins by Western blot analysis Inhibition of B-Raf-mediated Erk phosphorylation in human HMEC cells after 60 mins by Western blot analysis	[PMID: 22222036]
HT-29	EC₅₀	0.028 μM Compound: 6, SB-590885	Inhibition of B-Raf V600E mutant-mediated Erk phosphorylation in human HT-29 cells after 60 mins by Western blot analysis Inhibition of B-Raf V600E mutant-mediated Erk phosphorylation in human HT-29 cells after 60 mins by Western blot analysis	[PMID: 22222036]
PrEC	EC₅₀	1.1 μM Compound: 6, SB-590885	Inhibition of B-Raf-mediated Erk phosphorylation in human PREC cells after 60 mins by Western blot analysis Inhibition of B-Raf-mediated Erk phosphorylation in human PREC cells after 60 mins by Western blot analysis	[PMID: 22222036]
SK-MEL-2	EC₅₀	1.1 μM Compound: 6, SB-590885	Growth inhibition of human SK-MEL-2 cells expressing wild-type B-Raf and N-Ras2 Q61R mutant after 72 hrs by WST-1 assay Growth inhibition of human SK-MEL-2 cells expressing wild-type B-Raf and N-Ras2 Q61R mutant after 72 hrs by WST-1 assay	[PMID: 22222036]

In Vitro

SB-590885 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). SB-590885 displays potent selectivity over 46 other kinases. Unlike the multi-kinase inhibitor BAY43-9006, SB-590885 stabilizes the oncogenic B-Raf kinase domain in an active configuration. In Colo205, HT29, A375P, SKMEL28, and MALME-3M cells expressing oncogenic B-Raf^V600E, SB-590885 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. SB-590885 decreases anchorage-independent growth of melanoma cell lines in a BRAF mutant-selective manner^[1].?SB-590885 displays high affinity for B-Raf with K_d 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 SB-590885 with IC₅₀ of <1 μM. Increased levels of cyclin D1 resulting from genomic amplification mediate SB-590885 resistance in B-Raf V600E-mutated melanomas^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

Administration of SB-590885 potently decreases tumorigenesis in murine xenografts established from mutant B-Raf-expressing A375P melanoma cells, and modestly inhibits tumor growth^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Molecular Weight

453.54

Formula

C₂₇H₂₇N₅O₂

CAS No.

405554-55-4

Appearance

Solid

Color

White to yellow

SMILES

O/N=C1CCC2=CC(C3=C(NC(C4=CC=C(C=C4)OCCN(C)C)=N3)C5=CC=NC=C5)=CC=C/12

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	2 years
	-20°C	1 year

Solvent & Solubility

In Vitro:

DMSO : 10 mg/mL (22.05 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	2.2049 mL	11.0244 mL	22.0488 mL
5 mM	0.4410 mL	2.2049 mL	4.4098 mL
10 mM	0.2205 mL	1.1024 mL	2.2049 mL

View the 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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Molarity Calculator
Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

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.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (5.51 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.
Protocol 2

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (5.51 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.
Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.5 mg/mL (5.51 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

DMSO +

Tween-80 +

Saline

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.

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).

Calculation results:

Working solution concentration: mg/mL

Method for preparing stock solution: mg drug dissolved in μL DMSO (Stock solution concentration: mg/mL).

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).

Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.

If the continuous dosing period exceeds half a month, please choose this protocol carefully.

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

Purity: 99.77%

Select Batch:

Data Sheet (281 KB) SDS (251 KB)

COA (251 KB) HNMR (136 KB) RP-HPLC (138 KB) LCMS (251 KB)

Handling Instructions (2659 KB)

References

[1]. King AJ, et al. Demonstration of a genetic therapeutic index for tumors expressing oncogenic BRAF by the kinase inhibitor SB-590885. Cancer Res, 2006, 66(23), 11100-11105. [Content Brief]

[2]. Takle AK, et al. The identification of potent and selective imidazole-based inhibitors of B-Raf kinase. Bioorg Med Chem Lett, 2006, 16(2), 378-381. [Content Brief]

[3]. Smalley KS, et al. Increased cyclin D1 expression can mediate BRAF inhibitor resistance in BRAF V600E-mutated melanomas. Mol Cancer Ther, 2008, 7(9), 2876-2883. [Content Brief]

Cell Assay ^[1]	For proliferation assays, cells are treated with compounds in 0.1% DMSO and incubated for 72 hours at 37°C, 5% CO₂. 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, according to the manufacturer's instructions. Data is acquired and analyzed using CellQuest v3.3 software. Anchorage-independent growth assays are done as described elsewhere, with inhibitors or DMSO vehicle included in the agar layer. Cultures are re-fed with media and inhibitor or DMSO every 5 to 7 days for a total of 28 days. Colonies are visualized and photographed by conventional light microscopy and quantified by counting on a grid in triplicate. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration ^[1]	The pharmacokinetic properties and safety of SB-590885, following i.p. injection, are determined and 50 mg/kg daily injections are found to give therapeutic levels with minimal body weight changes. Tumors are initiated in 8- to 12-week-old female nude mice by s.c. injection of 5×10⁶ A375P cells in Matrigel suspension, and 3 weeks after tumor induction when the tumors had reached a volume of 150 to 250 mm³, mice are randomized into groups of eight prior to treatment. Animals are treated with vehicle [2% N,N-dimethylacetamide, 2% Cremophor EL, and 96% acidified water (pH 4-5)], or vehicle containing 50 mg/kg of SB-590885 daily for 21 days. A cohort of mice treated with SB-590885 are then observed an additional 14 days following cessation of treatment. Tumor volume is measured for 55 days by calipers twice weekly. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
References	[1]. King AJ, et al. Demonstration of a genetic therapeutic index for tumors expressing oncogenic BRAF by the kinase inhibitor SB-590885. Cancer Res, 2006, 66(23), 11100-11105. [Content Brief] [2]. Takle AK, et al. The identification of potent and selective imidazole-based inhibitors of B-Raf kinase. Bioorg Med Chem Lett, 2006, 16(2), 378-381. [Content Brief] [3]. Smalley KS, et al. Increased cyclin D1 expression can mediate BRAF inhibitor resistance in BRAF V600E-mutated melanomas. Mol Cancer Ther, 2008, 7(9), 2876-2883. [Content Brief]

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg

DMSO	1 mM	2.2049 mL	11.0244 mL	22.0488 mL	55.1219 mL
	5 mM	0.4410 mL	2.2049 mL	4.4098 mL	11.0244 mL
	10 mM	0.2205 mL	1.1024 mL	2.2049 mL	5.5122 mL
	15 mM	0.1470 mL	0.7350 mL	1.4699 mL	3.6748 mL
	20 mM	0.1102 mL	0.5512 mL	1.1024 mL	2.7561 mL

SB-590885 Related Classifications

Help & FAQs

Do most proteins show cross-species activity?
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

SB-590885405554-55-4SB590885SB 590885RafRaf kinasesInhibitorinhibitorinhibit

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SB-590885

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SB-590885 Related Antibodies

5 Publications Citing Use of MCE SB-590885

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•Related Screening Libraries:

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•Related Proteins:

View All Raf Isoform Specific Products:

Biological Activity

Protocol

Purity & Documentation

References

Customer Review

SB-590885 Related Antibodies

Molarity Calculator

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Complete Stock Solution Preparation Table

SB-590885 Related Classifications

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