2. MAPK/ERK Pathway
  3. Raf
  4. BI-882370

BI-882370 is a potent and selective RAF kinase inhibitor that binds to the ATP binding site of the kinase positioned in the DFG-out (inactive) conformation of the BRAF kinase. BI-882370 (BI 882370) inhibits the oncogenic BRAFV600E-mutant, the WT BRAF and CRAF kinases with IC50s of 0.4, 0.8, and 0.6 nM, respectively. BI-882370 also inhibits SRC family kinases.

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

BI-882370 Chemical Structure

BI-882370 Chemical Structure

CAS No. : 1392429-79-6

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Based on 1 publication(s) in Google Scholar

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Description

BI-882370 is a potent and selective RAF kinase inhibitor that binds to the ATP binding site of the kinase positioned in the DFG-out (inactive) conformation of the BRAF kinase. BI-882370 (BI 882370) inhibits the oncogenic BRAFV600E-mutant, the WT BRAF and CRAF kinases with IC50s of 0.4, 0.8, and 0.6 nM, respectively. BI-882370 also inhibits SRC family kinases[1].

IC50 & Target[1]

Braf

0.6 nM (IC50)

c-Raf

0.8 nM (IC50)

BRafV600E

0.4 nM (IC50)

Cellular Effect
Cell Line Type Value Description References
A-375 IC50
0.9 nM
Compound: 9; BI882370
Cytotoxicity against human A375 cells harboring BRAF V600E mutant after 72 hrs by alamar blue assay
Cytotoxicity against human A375 cells harboring BRAF V600E mutant after 72 hrs by alamar blue assay
[PMID: 29461827]
A-375 IC50
6.3 nM
Compound: 4; BI882370
Cytotoxicity in human A375 cells assessed as reduction in cell viability by Cell-titer-Lumi assay
Cytotoxicity in human A375 cells assessed as reduction in cell viability by Cell-titer-Lumi assay
[PMID: 32223235]
HT-29 IC50
1.7 nM
Compound: 4; BI882370
Cytotoxicity in human HT-29 cells assessed as reduction in cell viability by Cell-titer-Lumi assay
Cytotoxicity in human HT-29 cells assessed as reduction in cell viability by Cell-titer-Lumi assay
[PMID: 32223235]
In Vitro

BI-882370 (0.9-6000 nM; 3 days) inhibits the BRAF-mutant human melanoma and colorectal cancer cells proliferation with a EC50 range of 1-10 nM[1].
BI 882370 (0.1-100 nM, 0.1-3000 nM; 2 hours) results in a reduction of p-MEK1/2, p-ERK1/2 and cyclin D1/D2 expression in BRAFV600E-mutant A375 cells; induces phosphorylation of MEK1/2 and enhanced phosphorylation of ERK1/2 in WT BRO cells (3-300 nM)[1].
BI 882370 (0.1-100 nM, 0.1-3000 nM; 24 hours) suppresses cyclin D1/D2 expression, induces Kip1/p27 expression at concentrations of 1 nM or higher in BRAFV600E-mutant A375 cells, expression of cyclins D1/D2 or Kip1/p27 is not affected in WT BRO cells[1].

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

BI-882370 Related Antibodies

Cell Proliferation Assay[1]

Cell Line: BRAF-mutant and WT melanoma cell lines (A101D, A375, SK-MEL-28, G-361, and BRO); Colorectal cancer cell lines (COLO 205, HT-29, LS411N, and HCT-116)
Concentration: 0.9-6000 nM
Incubation Time: 3 days
Result: Showed a EC50 range of 1-10 nM in an extended panel of BRAF-mutant human melanoma and colorectal cancer cell; while proliferation of BRAF WT cells was inhibited with EC50 >1 μM.

Western Blot Analysis[1]

Cell Line: BRAFV600E-mutant A375 cells; BRAF WT, NRAS-mutant BRO (WT BRO) cells
Concentration: 0.1-100 nM; 0.1-3000 nM
Incubation Time: 2 hours; 24 hours
Result: Resulted in a reduction of phospho-MEK1/2 signals and cyclin D1/D2 expression in BRAFV600E-mutant A375 cells.
In Vivo

BI-882370 (deliver orally; 25 mg/kg, 50 mg/kg; twice daily; 2 weeks) is efficacious in multiple mouse models of BRAF-mutant melanomas and colorectal carcinomas, shows superior efficacy compared with Vemurafenib, Dabrafenib, or Trametinib[1].
BI-882370 (deliver orally; 25 mg/kg; twice daily; 40 days) developes resistance within 3 weeks, but resistance is not observed during 5 weeks of second-line therapy in combination with trametinib[1].
BI-882370 (deliver orally; 60 mg/kg; once daily; 2 weeks) indicates lack of toxicity in terms of clinical chemistry, hematology, pathology, and toxicogenomics in rats[1].

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

Animal Model: Human melanoma xenografts in nude mice with BRAF-mutant melanomas and colorectal carcinomas cells (A375, COLO 205; G-361, HT-29 cells)[1]
Dosage: 25 mg/kg; 50 mg/kg
Administration: Deliver orally; 25 mg/kg, 50 mg/kg; twice daily; 2 weeks
Result: Regressed tumors partially, upon discontinuation, tumor regrowth was markedly delayed.
Molecular Weight

569.67

Formula

C28H33F2N7O2S
CAS No.
Appearance

Solid

Color

Off-white to gray

SMILES

CCCS(=O)(NC1=CC=C(F)C(N2C=C(C3=CN=CN=C3)C4=NC(N(C5CCN(CC)CC5)C)=CC=C42)=C1F)=O
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 : 17.86 mg/mL (31.35 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

H2O : < 0.1 mg/mL (insoluble)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 1.7554 mL 8.7770 mL 17.5540 mL
5 mM 0.3511 mL 1.7554 mL 3.5108 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)

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

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start)

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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: ≥ 1.79 mg/mL (3.14 mM); Clear solution

    This protocol yields a clear solution of ≥ 1.79 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (17.9 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: ≥ 1.79 mg/mL (3.14 mM); Clear solution

    This protocol yields a clear solution of ≥ 1.79 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (17.9 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.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

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(per animal)

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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: 99.16%

SDS (252 KB)

COA (252 KB) HNMR (234 KB) LCMS (140 KB)

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, 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.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 1.7554 mL 8.7770 mL 17.5540 mL 43.8851 mL
5 mM 0.3511 mL 1.7554 mL 3.5108 mL 8.7770 mL
10 mM 0.1755 mL 0.8777 mL 1.7554 mL 4.3885 mL
15 mM 0.1170 mL 0.5851 mL 1.1703 mL 2.9257 mL
20 mM 0.0878 mL 0.4389 mL 0.8777 mL 2.1943 mL
25 mM 0.0702 mL 0.3511 mL 0.7022 mL 1.7554 mL
30 mM 0.0585 mL 0.2926 mL 0.5851 mL 1.4628 mL
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BI-882370 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:

BI-8823701392429-79-6BI882370BI 882370RafRaf kinasesInhibitorinhibitorinhibit

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