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Purity: ≥98%
BI-882370 (BI 882370), structurally similar to vermurafenib, is a novel, highly potent and selective BRAF inhibitor with anticancer activity. In the DFG-out (inactive) conformation of the BRAF kinase, it binds to the ATP site of the RAF kinase. Given that commercial BRAF inhibitors bind to the DFG-in conformation, its binding to the DFG-out conformation is special. With IC50 values of 0.4, 0.8, and 0.6 nM, respectively, BI-882370 inhibits the oncogenic BRAFV600E-mutant, WT BRAF, and CRAF kinases. SRC family kinases are also inhibited by BI-882370. With 100× higher potency (1-10 nmol/L) than vemurafenib, BI 882370 prevents the proliferation of human BRAF-mutant melanoma cells.
Targets |
Braf (Ki = 2 nM); JNK1 (IC50 = 45 nM); JNK2 (Ki = 4 nM); JNK2 (Ki = 160 nM); JNK3 (Ki = 52 nM)
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ln Vitro |
BI-882370 (0.9-6000 nM; 3 days) has an EC50 range of 1–10 nM and inhibits the proliferation of human melanoma and colorectal cancer cells that have the BRAF mutation[1].
BI 882370 (0.1-100 nM, 0.1-3000 nM; 2 hours) reduces the expression of p-MEK1/2, p-ERK1/2, and cyclin D1/D2 in BRAFV600E-mutant A375 cells; in WT BRO cells, it increases the phosphorylation of ERK1/2 and phosphorylates MEK1/2 (3–300 nM)[1]. In BRAFV600E-mutant A375 cells, BI 882370 (0.1-100 nM, 0.1-3000 nM; 24 hours) inhibits cyclin D1/D2 expression and increases Kip1/p27 expression at concentrations of 1 nM or higher. Expression of cyclins D1/D2 or Kip1/p27 is unaffected in WT BRO cells. |
ln Vivo |
BI-882370 (deliver orally; 25 mg/kg, 50 mg/kg; twice daily; 2 weeks) is more effective than Vemurafenib, Dabrafenib, or Trametinib in a number of mouse models of colorectal and BRAF-mutant melanoma[1].
BI-882370 (deliver orally; 25 mg/kg; twice daily; 40 days) develops resistance within three weeks, but trametinib-assisted second-line therapy for five weeks does not reveal resistance[1]. BI-882370 (deliver orally; 60 mg/kg; once daily; 2 weeks) shows no toxicity in rats when measured by clinical chemistry, hematology, pathology, and toxicogenomics[1]. |
Animal Protocol |
Human melanoma xenografts in nude mice with BRAF-mutant melanomas and colorectal carcinomas cells (A375, COLO 205; G-361, HT-29 cells)[1]
25 mg/kg; 50 mg/kg Deliver orally; 25 mg/kg, 50 mg/kg; twice daily; 2 weeks |
References |
Molecular Formula |
C28H33F2N7O2S
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Molecular Weight |
569.669131040573
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Exact Mass |
569.680
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Elemental Analysis |
C, 59.03; H, 5.84; F, 6.67; N, 17.21; O, 5.62; S, 5.63
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CAS # |
1392429-79-6
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Related CAS # |
1392429-79-6
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Appearance |
Solid powder
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SMILES |
CCCS(=O)(=O)NC1=C(C(=C(C=C1)F)N2C=C(C3=C2C=CC(=N3)N(C)C4CCN(CC4)CC)C5=CN=CN=C5)F
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InChi Key |
AEJACXAFHXBVHF-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C28H33F2N7O2S/c1-4-14-40(38,39)34-23-7-6-22(29)28(26(23)30)37-17-21(19-15-31-18-32-16-19)27-24(37)8-9-25(33-27)35(3)20-10-12-36(5-2)13-11-20/h6-9,15-18,20,34H,4-5,10-14H2,1-3H3
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Chemical Name |
N-[3-[5-[(1-ethylpiperidin-4-yl)-methylamino]-3-pyrimidin-5-ylpyrrolo[3,2-b]pyridin-1-yl]-2,4-difluorophenyl]propane-1-sulfonamide
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Synonyms |
BI882370; BI 882370; BI-882370
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HS Tariff Code |
2934.99.9001
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
DMSO : ~5 mg/mL (~8.78 mM)
H2O : < 0.1 mg/mL |
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Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 :Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400  (Please use freshly prepared in vivo formulations for optimal results.) |
Preparing Stock Solutions | 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 | |
10 mM | 0.1755 mL | 0.8777 mL | 1.7554 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Structure of BI 882370, dabrafenib, and their co-crystals with BRAF WT kinase. Mol Cancer Ther . 2016 Mar;15(3):354-65. td> |
First-line therapy of human melanoma xenografts in nude mice. A, mice bearing A375 tumors (BRAFV600E homozygous) were treated with BI 882370 at 25 mg/kg twice daily (bid), with vemurafenib at 120 mg/kg once daily (qd), or with dabrafenib at 60 mg/kg once daily. Mol Cancer Ther . 2016 Mar;15(3):354-65. td> |