Entrectinib (Rxdx-101)

CatalogusnummerS7998 Batch:S799803

Afdrukken

Technische gegevens

Formule

C31H34F2N6O2
Moleculair gewicht 560.64 CAS-nr. 1108743-60-7
Oplosbaarheid (25°C)* In vitro DMSO 100 mg/mL (178.36 mM)
Ethanol 75 mg/mL (133.77 mM)
Water 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 Entrectinib is een oraal biologisch beschikbare pan-TrkA/B/C-, ROS1- en ALK-remmer met IC50 variërend tussen 0,1 en 1,7 nM. Entrectinib (RXDX-101) induceert autophagy. Fase 2.
Doelen
TrkA TrkB TrkC ROS1 ALK
In vitro

Entrectinib blokkeert selectief de proliferatie van ALK-afhankelijke cellijnen en remt krachtig de ALK-afhankelijke signalering. Deze verbinding remt ook sterk de celgroei van de NSCLC-cellijn NCI-H2228 met de EML4-ALK-rearrangement.

In vivo

Bij muizen met Karpas-299- en SR-786-xenografts induceert Entrectinib (p.o.) volledige tumorregressie. Bij NPM-ALK-transgene muizen induceert deze verbinding volledige regressie van tumormassa's waargenomen in de thymus en in lymfeklieren.

In het NB-xenograftmodel verbeterde deze verbinding cotreatment de werkzaamheid van conventionele chemotherapie.

Protocol (uit referentie)

Referenties

  • https://pubmed.ncbi.nlm.nih.gov/26457764/
  • http://mct.aacrjournals.org/content/8/12_Supplement/A244.short
  • http://cancerres.aacrjournals.org/content/75/15_Supplement/5390
  • https://pubmed.ncbi.nlm.nih.gov/36101520/
  • https://pubmed.ncbi.nlm.nih.gov/33229458/

Klantproductvalidatie

Tumor cells were treated with entrectinib (10 nmol/L) for 4 hours or c-PARP for 48 hours, and harvested lysates were assessed by Western blotting. Data shown are representative of three independent experiments with similar results.

Gegevens van [ , , Clin Cancer Res, 2018, 24(10):2357-2369 ]

(A) We transfected the EGFP/Eluc gene into KM12SM cells to establish KM12SM/Eluc cells. KM12SM/Eluc cells were inoculated into the brain of SCID mice. The mice were treated daily with or without entrectinib (15 mg/kg) for 37 days until the bioluminescence increased. Mean ± SE of total flux are shown in the lower panel. Then, the entrectinib-treated brain tumor was harvested at the point indicated by the orange triangle and cultured in vitro. The expanded tumor cells were named KM12SM-ER. (B) The sensitivity of KM12SM-ER and KM12SM cells to entrectinib was determined through cell viability assays, using a CCK-8 kit. The data (mean ± standard deviation [SD] of triplicate cultures) shown are representative of three independent experiments with similar results. (C) Tumor cells were treated with entrectinib (10 nmol/L) for 4 h or c-PARP for 48 h, and harvested lysates were assessed by western blotting. Data shown are representative of three independent experiments with similar results.

Gegevens van [ , , Clin Cancer Res, 2018, doi: 10.1158/1078-0432.CCR-17-1623 ]

KM12C and KM12SM cells were treated with crizotinib (1 μmol/L) or entrectinib (1 μmol/L) for 2 h. Immunoblots of cell lysates from these treated cell lines are shown. The data are representative of three independent experiments, showing similar results.

Gegevens van [ , , Cancer Med, 2017, 6(12):2972-2983 ]

The effect of kinase inhibitors on signal transduction in human cancer cell lines in vitro. H1975 cells were treated with osimertinib (1 μmol/L) for 2 h. NUGC4 cells were treated with crizotinib (1 μmol/L) for 2 h, and then stimulated with HGF (50 ng/mL) for 10 min. KM12C and KM12SM cells were treated with crizotinib (1 μmol/L) or entrectinib (1 μmol/L) for 2 h. Immunoblots of cell lysates from these treated cell lines are shown.

Gegevens van [ , , Cancer Med, 2017, 6(12):2972-2983 ]

Sellecks Entrectinib (Rxdx-101) Is geciteerd door 61 Publicaties

Targeting proteostasis in multiple myeloma through inhibition of LTK [ Leukemia, 2025, 10.1038/s41375-025-02682-8] PubMed: 40634511
Methylstat sensitizes ovarian cancer cells to PARP-inhibition by targeting the histone demethylases JMJD1B/C [ Cancer Gene Ther, 2025, 10.1038/s41417-025-00874-z] PubMed: 39915607
Zidesamtinib Selective Targeting of Diverse ROS1 Drug-Resistant Mutations [ Mol Cancer Ther, 2025, 10.1158/1535-7163.MCT-25-0025] PubMed: 40299789
Development of PROTACs for targeted degradation of oncogenic TRK fusions [ bioRxiv, 2025, 2025.06.18.660465] PubMed: 40666929
Clinical efficacy and identification of factors confer resistance to afatinib (tyrosine kinase inhibitor) in EGFR-overexpressing esophageal squamous cell carcinoma [ Signal Transduct Target Ther, 2024, 9(1):153] PubMed: 38937446
Pharmacological inhibition of PDGF-C/neuropilin-1 interaction: A novel strategy to reduce melanoma metastatic potential [ Biomed Pharmacother, 2024, 176:116766] PubMed: 38788599
Acquired NF2 mutation confers resistance to TRK inhibition in an ex vivo LMNA::NTRK1-rearranged soft-tissue sarcoma cell model [ J Pathol, 2024, 10.1002/path.6282] PubMed: 38613194
Acquired NF2 mutation confers resistance to TRK inhibition in an ex vivo LMNA::NTRK1-rearranged soft-tissue sarcoma cell model [ J Pathol, 2024, 263(2):257-269] PubMed: 38613194
LTK mutations responsible for resistance to lorlatinib in non-small cell lung cancer harboring CLIP1-LTK fusion [ Commun Biol, 2024, 7(1):412] PubMed: 38575808
Patient-derived rhabdomyosarcoma cells recapitulate the genetic and transcriptomic landscapes of primary tumors [ iScience, 2024, 27(10):110862] PubMed: 39319271

RETOURBELEID
Selleck Chemicals onvoorwaardelijke retourbeleid zorgt voor een soepele online winkelervaring voor onze klanten. Als u op enigerlei wijze ontevreden bent met uw aankoop, kunt u elk artikel(en) binnen 7 dagen na ontvangst retourneren. In geval van problemen met de productkwaliteit, zowel protocolgerelateerde als productgerelateerde problemen, kunt u elk artikel(en) binnen 365 dagen na de oorspronkelijke aankoopdatum retourneren. Volg de onderstaande instructies bij het retourneren van producten.

VERZENDING EN OPSLAG
Selleck producten worden bij kamertemperatuur vervoerd. Als u het product op kamertemperatuur ontvangt, wees dan gerust, de Selleck kwaliteitsinspectieafdeling heeft experimenten uitgevoerd om te controleren of de normale temperatuurplaatsing van één maand de biologische activiteit van poederproducten niet beïnvloedt. Na ontvangst dient u het product op te slaan volgens de vereisten beschreven in het gegevensblad. De meeste Selleck producten zijn stabiel onder de aanbevolen omstandigheden.

NIET VOOR HUMANE, VETERINAIRE DIAGNOSTISCHE OF THERAPEUTISCHE DOELEINDEN.