Bemcentinib (R428)

CatalogusnummerS2841 Batch:S284108

Afdrukken

Technische gegevens

Formule

C30H34N8
Moleculair gewicht 506.64 CAS-nr. 1037624-75-1
Oplosbaarheid (25°C)* In vitro DMSO 9 mg/mL (17.76 mM)
Water Insoluble
Ethanol Insoluble
In vivo (Voeg oplosmiddelen afzonderlijk en in volgorde toe aan het product.)
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <1 mg/ml betekent licht oplosbaar of onoplosbaar.
* Houd er rekening mee dat Selleck de oplosbaarheid van alle verbindingen intern test en de werkelijke oplosbaarheid enigszins kan afwijken van gepubliceerde waarden. Dit is normaal en is te wijten aan lichte batch-tot-batch variaties.
* Verzending op kamertemperatuur (Stabiliteitstests tonen aan dat dit product zonder koelmaatregelen kan worden verzonden.)

Voorbereiden van stamoplossingen

Biologische activiteit

Beschrijving Bemcentinib (R428, BGB324) is een remmer van Axl met een IC50 van 14 nM, wat een >100-voudige selectiviteit voor Axl boven Abl aantoont. Deze verbinding is ook meer dan 50- tot 100-voudig selectief voor Axl versus Mer en Tyro3, en vertoont een 100-voudig grotere selectiviteit in vergelijking met InsR, EGFR, HER2 en PDGFR.
Doelen
Axl
(Cell-free assay)
14 nM
In vitro Bemcentinib (R428) blocks the catalytic and procancerous activities of Axl. It inhibits Axl with low nanomolar activity and blocks Axl-dependent events, including Akt phosphorylation, breast cancer cell invasion, and proinflammatory cytokine production. In a recent study, this compound shows a mean IC50 dose of ∼ 2.0μM for the primary CLL B cells after 24 hours of treatment and normal B-, T-, and natural killer (NK) cells show no significant amount of cell death at this dose of R428 (2.5 μM) under similar experimental conditions.
In vivo Pharmacologic investigations reveal favorable exposure after oral administration of Bemcentinib (R428), such that treated tumors display a dose-dependent reduction in expression of the cytokine granulocyte macrophage colony-stimulating factor and the epithelial-mesenchymal transition transcriptional regulator Snail. In support of an earlier study, it inhibits angiogenesis in corneal micropocket and tumor models. This compound also reduces metastatic burden and extends survival in MDA-MB-231 intracardiac and 4T1 orthotopic (median survival, >80 days compared with 52 days; P < 0.05) mouse models of breast cancer metastasis.

Protocol (uit referentie)

Dierstudie:

[1]
  • Dierlijke modellen

    MDA-MB-231-luc-D3H2LN Intracardiac Model

  • Doseringen

    125 mg/kg

  • Toediening

    Oral, twice daily

Referenties

  • https://pubmed.ncbi.nlm.nih.gov/20145120/
  • https://pubmed.ncbi.nlm.nih.gov/21135257/

Klantproductvalidatie

Cetuximab-resistant cells are sensitive to therapeutic blockade of AXL activity with the AXL TKI R428. Cells were treated with vehicle (-) or indicated doses of R428 for 24 hours before harvesting whole-cell lysate and immunoblotting for the indicated proteins. α-Tubulin was used as a loading control.

Gegevens van [ Cancer Res , 2014 , 74(18), 5152-64 ]

Axl inhibitor promotes the apoptosis induced by ALK-TKIs. (A) After treated with crizotinib (100 nM), BGB324 (300 nM) or their combination for 48 h, cell apoptosis was determined by flow cytometry. (B) The induction of apoptosis by ceritinib (100 nM), BGB324 (300 nM) or their combination was examined. (C and D) Cells were treated with crizotinib (100 nM), BGB324 (300 nM) or their combination for 48 h, then whole-cell lysates were collected and the levels of indicated protein were analyzed by Western blot in (C) NB1643 and (D) SHSY5Y cells. *P < 0.05 for the indicated comparisons; ns, not significant.

Gegevens van [ Biochem Bioph Res Co , 2014 , 10.1016/j.bbrc.2014.10.126 ]

<p>B) The processing of AXL is increased by an AXL kinase inhibitor. Panc-28 cells were incubated overnight with DMSO or 150 nM R428, a selective AXL kinase inhibitor, before examining by Western blot the levels of endogenous AXL-FL and AXL-CTF (C-20; left). Levels of AXL-CTF in DAPT-treated cells were quantified as described above and unpaired Student’s t test was employed for the analysis (right). Data are shown as means±SEM (n = 4). ***P<0.001.</p>

, , FASEB J, 2017, 31(4):1382-1397

Flow cytometry analysis showing band 3/α4 integrin expression of luciferase and TET2-knockdown CFU-E cells cultured for 13 days in the presence of DMSO or 0.2 μM R428.

Gegevens van [ , , Blood, 2018, doi:10.1182/blood-2018-05-853291 ]

Selleck's Bemcentinib (R428) Is geciteerd door 142 Publicaties

Pre-adaptation of stem cell-derived islet organoids to hypoxia via zinc transportation inhibition drives angiogenesis [ Cell Stem Cell, 2026, 33(4):676-694.e10] PubMed: 41932324
A pancreatic cancer organoid biobank links multi-omics signatures to therapeutic response and clinical evaluation of statin combination therapy [ Cell Stem Cell, 2025, S1934-5909(25)00265-6] PubMed: 40812300
Tumor initiating cells escape tumor immunity via CCL8 from tumor-associated macrophages in mice [ J Clin Invest, 2025, e180893] PubMed: 39774471
Axl inhibitor-mediated reprogramming of the myeloid compartment of the in vitro tumor microenvironment is influenced by prior targeted therapy treatment [ Front Immunol, 2025, 16:1601420] PubMed: 40539073
Synaptotagmin-7 deficit causes insulin hypoactivity and contributes to behavioral alterations in mice [ iScience, 2025, 28(5):112354] PubMed: 40330888
Geranylgeranyl diphosphate synthase deficiency impairs efferocytosis and resolution of acute lung injury [ Respir Res, 2025, 26(1):189] PubMed: 40380222
FRA1 drives melanoma metastasis through an actionable transcriptional network [ bioRxiv, 2025, 2025.06.07.658418] PubMed: 40661443
Directed differentiation of pancreatic δ cells from human pluripotent stem cells [ Nat Commun, 2024, 15(1):6344] PubMed: 39068220
CD276-dependent efferocytosis by tumor-associated macrophages promotes immune evasion in bladder cancer [ Nat Commun, 2024, 15(1):2818] PubMed: 38561369
AXL-specific single domain antibodies show diagnostic potential and anti-tumor activity in Acute Myeloid Leukemia [ Theranostics, 2024, 14(7):2656-2674] PubMed: 38773967

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NIET VOOR HUMANE, VETERINAIRE DIAGNOSTISCHE OF THERAPEUTISCHE DOELEINDEN.