Bemcentinib
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MedKoo CAT#: 401810

CAS#: 1037624-75-1

Description: Bemcentinib, also known as BGB-324 or R428, is a selective small molecule inhibitor of Axl kinase, which showed activity to blocks tumor spread and prolongs survival in models of metastatic breast cancer. The receptor tyrosine kinase Axl may play an important role in cancer progression, invasion, metastasis, drug resistance, and patient mortality. R428 inhibits Axl with low nanomolar activity and blocked Axl-dependent events, including Akt phosphorylation, breast cancer cell invasion, and proinflammatory cytokine production.


Chemical Structure

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Bemcentinib
CAS# 1037624-75-1

Theoretical Analysis

MedKoo Cat#: 401810
Name: Bemcentinib
CAS#: 1037624-75-1
Chemical Formula: C30H34N8
Exact Mass: 506.29064
Molecular Weight: 506.64
Elemental Analysis: C, 71.12; H, 6.76; N, 22.12

Price and Availability

Size Price Availability Quantity
25.0mg USD 150.0 Ready to ship
50.0mg USD 250.0 Ready to ship
100.0mg USD 450.0 Ready to ship
200.0mg USD 750.0 Ready to ship
500.0mg USD 1650.0 Ready to ship
1.0g USD 2950.0 Ready to ship
2.0g USD 5250.0 Ready to ship
5.0g USD 8650.0 Ready to ship
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Related CAS #: 1037624-75-1   1037624-91-1 (racemic)  

Synonym: BGB324; BGB-324; BGB 324; R 428; R-428; R428; Bemcentinib

IUPAC/Chemical Name: (S)-1-(6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl)-N3-(7-(pyrrolidin-1-yl)-6,7,8,9-tetrahydro-5H-benzo[7]annulen-2-yl)-1H-1,2,4-triazole-3,5-diamine

InChi Key: KXMZDGSRSGHMMK-VWLOTQADSA-N

InChi Code: InChI=1S/C30H34N8/c31-29-33-30(32-24-13-10-20-11-14-25(15-12-22(20)18-24)37-16-3-4-17-37)36-38(29)27-19-23-8-5-7-21-6-1-2-9-26(21)28(23)35-34-27/h1-2,6,9-10,13,18-19,25H,3-5,7-8,11-12,14-17H2,(H3,31,32,33,36)/t25-/m0/s1

SMILES Code: NC1=NC(NC2=CC=C3C(CC[C@@H](N4CCCC4)CC3)=C2)=NN1C5=NN=C6C(CCCC7=CC=CC=C76)=C5

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Biological target: Bemcentinib (R428) is a potent and selective inhibitor of Axl with an IC50 of 14 nM.
In vitro activity: To determine the effect of R428 on ESCC tumor cells, the expression levels of AXL in TE1 and KYSE150 cells were determined using western blotting. Both cell lines were found to express AXL and activated AXL (AXL phosphorylated at tyrosine residue 779; Fig. 1A). It was also confirmed that R428 treatment suppressed AXL activation in both TE1 and KYSE150 cells in a dose-dependent manner (Fig. 1B-E). AKT and ERK signaling are two major branches of AXL signaling, thus their responses to R428 were determined; it was identified that R428 treatment suppressed AKT and ERK signaling activation in a dose-dependent manner (Fig. 1B-E). Reference: Exp Ther Med. 2020 Nov; 20(5): 41. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480165/
In vivo activity: This study demonstrated the efficacy of R428, but not of BMS-777607 (Figure 1), in inhibiting ESCC cell growth. Although BMS-777607 has been found to inhibit cell growth in a xenograft model of gastric carcinoma and to suppress the metastatic phenotype of HGF-induced prostate cancer, this study did not observe a significant effect of BMS-777607 on the viability of either CE81T or KYSE-70 ESCC cells (Figure 1). In addition to viability, R428 also suppressed the migration activity of ESCC cells (Figure 4). R428 alone also significantly decreased ESCC tumor growth compared to vehicle in the mouse model (Figure 5), however, not as remarkably as cabozantinib did. Reference: Front Oncol. 2019; 9: 1138. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6851194/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 15.71 31.01

Preparing Stock Solutions

The following data is based on the product molecular weight 506.64 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Han S, Wang Y, Ge C, Gao M, Wang X, Wang F, Sun L, Li S, Dong T, Dang Z, Cui W, Zhang G, Liu N. Pharmaceutical inhibition of AXL suppresses tumor growth and invasion of esophageal squamous cell carcinoma. Exp Ther Med. 2020 Nov;20(5):41. doi: 10.3892/etm.2020.9169. Epub 2020 Sep 2. PMID: 32952632; PMCID: PMC7480165. 2. Zajac O, Leclere R, Nicolas A, Meseure D, Marchiò C, Vincent-Salomon A, Roman-Roman S, Schoumacher M, Dubois T. AXL Controls Directed Migration of Mesenchymal Triple-Negative Breast Cancer Cells. Cells. 2020 Jan 19;9(1):247. doi: 10.3390/cells9010247. PMID: 31963783; PMCID: PMC7016818. 3. Yang PW, Liu YC, Chang YH, Lin CC, Huang PM, Hua KT, Lee JM, Hsieh MS. Cabozantinib (XL184) and R428 (BGB324) Inhibit the Growth of Esophageal Squamous Cell Carcinoma (ESCC). Front Oncol. 2019 Nov 6;9:1138. doi: 10.3389/fonc.2019.01138. PMID: 31781483; PMCID: PMC6851194. 4. Landolt L, Furriol J, Babickova J, Ahmed L, Eikrem Ø, Skogstrand T, Scherer A, Suliman S, Leh S, Lorens JB, Gausdal G, Marti HP, Osman T. AXL targeting reduces fibrosis development in experimental unilateral ureteral obstruction. Physiol Rep. 2019 May;7(10):e14091. doi: 10.14814/phy2.14091. PMID: 31134766; PMCID: PMC6536582.
In vitro protocol: 1. Han S, Wang Y, Ge C, Gao M, Wang X, Wang F, Sun L, Li S, Dong T, Dang Z, Cui W, Zhang G, Liu N. Pharmaceutical inhibition of AXL suppresses tumor growth and invasion of esophageal squamous cell carcinoma. Exp Ther Med. 2020 Nov;20(5):41. doi: 10.3892/etm.2020.9169. Epub 2020 Sep 2. PMID: 32952632; PMCID: PMC7480165. 2. Zajac O, Leclere R, Nicolas A, Meseure D, Marchiò C, Vincent-Salomon A, Roman-Roman S, Schoumacher M, Dubois T. AXL Controls Directed Migration of Mesenchymal Triple-Negative Breast Cancer Cells. Cells. 2020 Jan 19;9(1):247. doi: 10.3390/cells9010247. PMID: 31963783; PMCID: PMC7016818.
In vivo protocol: 1. Yang PW, Liu YC, Chang YH, Lin CC, Huang PM, Hua KT, Lee JM, Hsieh MS. Cabozantinib (XL184) and R428 (BGB324) Inhibit the Growth of Esophageal Squamous Cell Carcinoma (ESCC). Front Oncol. 2019 Nov 6;9:1138. doi: 10.3389/fonc.2019.01138. PMID: 31781483; PMCID: PMC6851194. 2. Landolt L, Furriol J, Babickova J, Ahmed L, Eikrem Ø, Skogstrand T, Scherer A, Suliman S, Leh S, Lorens JB, Gausdal G, Marti HP, Osman T. AXL targeting reduces fibrosis development in experimental unilateral ureteral obstruction. Physiol Rep. 2019 May;7(10):e14091. doi: 10.14814/phy2.14091. PMID: 31134766; PMCID: PMC6536582.

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