Name: Entrectinib (Rxdx-101)
Brand: Selleck Chemicals
SKU: S7998
Rating: 5 (60 reviews)

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Kvalitetskontroll (Quality Control)

Batch: Renhet: 99.93%

99.93

Relaterade mål	EGFR VEGFR FGFR PDGFR c-Met Src MEK CSF-1R HER2 FLT3
Övrigt Trk receptor Inhibitorer	ANA-12 GW441756 7,8-Dihydroxyflavone GNF-5837 Selitrectinib (LOXO-195) LM22B-10 Altiratinib PF-06273340 CH7057288 N-Acetyl-5-hydroxytryptamine

Cellodling, behandling & arbetskoncentration
(Cell Culture, Treatment & Working Concentration)

Cellinjer	Analystyp	Koncentration	Inkubationstid	Aktivitetsbeskrivning	PMID
BAF3	Function assay		72 hrs	Inhibition of human TEL (336 residues) fused-TRKB (455 to 822 residues) (unknown origin) expressed in mouse BAF3 cells assessed as cell growth inhibition after 72 hrs by cell titer-glo assay, IC50 = 0.003 μM.	27003761
BAF3	Function assay		72 hrs	Inhibition of human TEL (336 residues) fused-TRKA (440 to 796 residues) (unknown origin) expressed in mouse BAF3 cells assessed as cell growth inhibition after 72 hrs by cell titer-glo assay, IC50 = 0.003 μM.	27003761
BAF3	Function assay		72 hrs	Inhibition of human TEL (336 residues) fused-TRKC (454 to 825 residues) (unknown origin) expressed in mouse BAF3 cells assessed as cell growth inhibition after 72 hrs by cell titer-glo assay, IC50 = 0.003 μM.	27003761
BAF3	Function assay		72 hrs	Inhibition of human TEL (336 residues) fused-ROS1 (1891 to 2347 residues) (unknown origin) expressed in mouse BAF3 cells assessed as cell growth inhibition after 72 hrs by cell titer-glo assay, IC50 = 0.005 μM.	27003761
KM12	Antiproliferative assay		72 hrs	Antiproliferative activity against human KM12 cells expressing TRKA protein incubated for 72 hrs by cell titer-glo assay, IC50 = 0.017 μM.	27003761
SU-DHL1	Antiproliferative assay		72 hrs	Antiproliferative activity against human SU-DHL1 cells expressing ALK protein incubated for 72 hrs by cell titer-glo assay, IC50 = 0.024 μM.	27003761
BAF3	Function assay		72 hrs	Inhibition of wild type EML4-ALK (unknown origin) expressed in mouse BAF3 cells assessed as cell growth inhibition after 72 hrs by cell titer-glo assay, IC50 = 0.028 μM.	27003761
KARPAS299	Antiproliferative assay		72 hrs	Antiproliferative activity against human KARPAS299 cells incubated for 72 hrs by cell titer-glo assay, IC50 = 0.031 μM.	27003761
SUP-M2	Antiproliferative assay		72 hrs	Antiproliferative activity against human SUP-M2 cells expressing ALK protein incubated for 72 hrs by cell titer-glo assay, IC50 = 0.041 μM.	27003761
BAF3	Function assay		72 hrs	Inhibition of EML4-ALK L1196M mutant (unknown origin) expressed in mouse BAF3 cells assessed as cell growth inhibition after 72 hrs by cell titer-glo assay, IC50 = 0.067 μM.	27003761
NCI-H2228	Antiproliferative assay		72 hrs	Antiproliferative activity against human NCI-H2228 cells expressing ALK protein incubated for 72 hrs by cell titer-glo assay, IC50 = 0.068 μM.	27003761
MV411	Antiproliferative assay		72 hrs	Antiproliferative activity against human MV411 cells incubated for 72 hrs by cell titer-glo assay, IC50 = 0.081 μM.	27003761
SR786	Antiproliferative assay		72 hrs	Antiproliferative activity against human SR786 cells expressing ALK protein incubated for 72 hrs by cell titer-glo assay, IC50 = 0.081 μM.	27003761
BAF3	Function assay		72 hrs	Inhibition of EML4-ALK G1202R mutant (unknown origin) expressed in mouse BAF3 cells assessed as cell growth inhibition after 72 hrs by cell titer-glo assay, IC50 = 0.897 μM.	27003761
BA/F3	Cytotoxicity assay		72 hrs	Cytotoxicity against mouse IL-3 dependent BA/F3 cells incubated for 72 hrs by cell titer-glo assay, IC50 = 2.104 μM.	27003761
KM12	Function assay		2 hrs	Inhibition of TPM3-TRKA phosphorylation in human KM12 cells at low concentration after 2 hrs by Western blot analysis	27003761
KM12	Function assay		2 hrs	Inhibition of TPM3-TRKA phosphorylation in human KM12 cells assessed as suppression of MAPK phosphorylation at low concentration after 2 hrs by Western blot analysis	27003761
KM12	Function assay		2 hrs	Inhibition of TPM3-TRKA phosphorylation in human KM12 cells assessed as suppression of PLCgamma1 phosphorylation at low concentration after 2 hrs by Western blot analysis	27003761
KM12	Function assay		2 hrs	Inhibition of TPM3-TRKA phosphorylation in human KM12 cells assessed as suppression of AKT phosphorylation at low concentration after 2 hrs by Western blot analysis	27003761
KM12	Function assay		2 hrs	Inhibition of TPM3-TRKA phosphorylation in human KM12 cells assessed as suppression of S6 phosphorylation at low concentration after 2 hrs by Western blot analysis	27003761
KARPAS299	Function assay	60 mg/kg	12 hrs	Ex vivo inhibition of NPM-ALK phosphorylation in SCID mouse xenografted with human KARPAS299 cells at 60 mg/kg, po administered as single dose measured after 12 hrs by Western blot analysis	27003761
KARPAS299	Function assay	60 mg/kg	18 hrs	Ex vivo inhibition of NPM-ALK phosphorylation in SCID mouse xenografted with human KARPAS299 cells at 60 mg/kg, po administered as single dose measured after 18 hrs by Western blot analysis	27003761
KARPAS299	Function assay	60 mg/kg	12 hrs	Ex vivo inhibition of NPM-ALK phosphorylation in SCID mouse xenografted with human KARPAS299 cells assessed as suppression of STAT3 phosphorylation at 60 mg/kg, po administered as single dose measured after 12 hrs by Western blot analysis	27003761
KARPAS299	Function assay	60 mg/kg	18 hrs	In vivo inhibition of NPM-ALK phosphorylation in SCID mouse xenografted with human KARPAS299 cells assessed as suppression of STAT3 phosphorylation at 60 mg/kg, po administered as single dose measured after 18 hrs by Western blot analysis	27003761
NCI-H2228	Antitumor assay	30 to 60 mg/kg	10 days	Antitumor activity against human NCI-H2228 cells xenografted in athymic nu/nu mouse assessed as tumor growth inhibition at 30 to 60 mg/kg, po bid administered for 10 days	27003761
NCI-H2228	Function assay	60 mg/kg	12 hrs	Ex vivo inhibition of EML4-ALK phosphorylation in athymic nu/nu mouse xenografted with human NCI-H2228 cells at 60 mg/kg, po administered as single dose measured after 12 hrs by Western blot analysis	27003761
NCI-H2228	Function assay	60 mg/kg	18 hrs	Ex vivo inhibition of EML4-ALK phosphorylation in athymic nu/nu mouse xenografted with human NCI-H2228 cells at 60 mg/kg, po administered as single dose measured after 18 hrs by Western blot analysis	27003761
NCI-H2228	Function assay	60 mg/kg	12 hrs	Ex vivo inhibition of EML4-ALK phosphorylation in athymic nu/nu mouse xenografted with human NCI-H2228 cells assessed as suppression of AKT phosphorylation at 60 mg/kg, po administered as single dose measured after 12 hrs by Western blot analysis	27003761
NCI-H2228	Function assay	60 mg/kg	18 hrs	Ex vivo inhibition of EML4-ALK phosphorylation in athymic nu/nu mouse xenografted with human NCI-H2228 cells assessed as suppression of AKT phosphorylation at 60 mg/kg, po administered as single dose measured after 18 hrs by Western blot analysis	27003761
KARPAS299	Antitumor assay	30 to 60 mg/kg	10 days	Antitumor activity against human KARPAS299 cells xenografted in SCID mouse assessed as tumor growth inhibition at 30 to 60 mg/kg, po bid administered for 10 days	27003761
KARPAS299	Antitumor assay	30 to 60 mg/kg	10 days	Antitumor activity against human KARPAS299 cells xenografted in SCID mouse assessed as tumor free cured mouse at 30 to 60 mg/kg, po bid administered for 10 days measured on day 90	27003761
KARPAS299	Function assay		2 hrs	Inhibition of NPM/ALK autophosphorylation in human KARPAS299 cells at very low concentration after 2 hrs by Western blot analysis	27003761
NCI-H2228	Function assay		2 hrs	Inhibition of NPM/ALK autophosphorylation in human NCI-H2228 cells at very low concentration after 2 hrs by Western blot analysis	27003761
Klicka för att visa mer experimentella data för cellinjer

Kemisk information, lagring & stabilitet (Chemical Information, Storage & Stability)

Molekylvikt	560.64	Formel	C₃₁H₃₄F₂N₆O₂	Lagring (från mottagningsdatumet)	3 år-20°Cpulver
CAS-nr	1108743-60-7	Ladda ner SDF		Lagring av stamlösningar	1 år-80°Ci lösningsmedel 1 månad-20°Ci lösningsmedel
Synonymer	RXDX-101, NMS-E628			Smiles	CN1CCN(CC1)C2=CC(=C(C=C2)C(=O)NC3=NNC4=C3C=C(C=C4)CC5=CC(=CC(=C5)F)F)NC6CCOCC6

Löslighet (Solubility)

In vitro
Batch:

DMSO : 100 mg/mL (178.36 mM)
(Fuktkontaminerad DMSO kan minska lösligheten. Använd färk, vattenfri DMSO.)

Ethanol : 100 mg/mL

Water : Insoluble

Molaritetsräknare

Massa	Koncentration	Volym	Molekylvikt
=	×	×

Utspädningsräknare Molekylviktsräknare

In vivo Batch:
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.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validerad av Selleck-laboratorier. Om du behöver justeringar av denna formulering, kontakta vårt säljteam för skräddarsydd testning.	5.000mg/ml (8.92mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to make it clear; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
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.
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.
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.
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.

In vivo-formuleringsräknare (Klar lösning)

Steg 1: Ange information nedan (Rekommenderas: Ett extra djur för att ta hänsyn till förluster under experimentet)

Dosering: mg/kg Djurens medelvikt: g Doseringsvolym per djur:μL Antal djur:

Steg 2: Ange in vivo-formuleringen (Detta är endast räknaren, inte formuleringen. Vänligen kontakta oss först om det inte finns någon in vivo-formulering i löslighetsavsnittet.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Beräkningsresultat:

Arbetskoncentration: mg/ml;

Metod för att bereda DMSO-stamlösning: mg substans förlöst i μL DMSO ( Stamlösningskoncentration mg/mL, Vänligen kontakta oss först om koncentrationen överskrider DMSO-lösligheten för denna batch av substansen. )

Metod för att bereda in vivo-formulering: Ta μL DMSO stamlösning, tillsätt sedanμL PEG300, blanda och klarna, tillsätt sedanμL Tween 80, blanda och klarna, tillsätt sedan μL ddH₂O, blanda och klarna.

Metod för att bereda in vivo-formulering: Ta μL DMSO stamlösning, tillsätt sedan μL Majsolja, blanda och klarna.

Obs: 1. Se till att vätskan är klar innan du tillsätter nästa lösningsmedel.
2. Se till att tillsätta lösningsmedlet/lösningsmedlen i ordning. Du måste se till att lösningen som erhålls i föregående tillsats är en klar lösning innan du fortsätter att tillsätta nästa lösningsmedel. Fysiska metoder som vortex, ultraljud eller varmt vattenbad kan användas för att underlätta upplösningen.

Verkningsmekanism (Mechanism of Action)

Targets/IC₅₀/Ki	TrkA TrkB TrkC ROS1 ALK
In vitro	Entrectinib selectively blocks proliferation of ALK-dependent cell lines and potently inhibits ALK‐dependent signaling. This compound also highly inhibits cell growth of the NSCLC cell line NCI‐H2228 bearing the EML4-ALK rearrangement.
In vivo	In mice bearing Karpas-299 and SR-786 xenografts, Entrectinib (p.o.) induces complete tumor regression. In NPM-ALK transgenic mice, this compound induces complete regression of tumor masses observed in the thymus and in lymph nodes. In the NB xenograft model, this compound cotreatment enhanced the efficacy of conventional chemotherapy.
Referenser	[1] https://pubmed.ncbi.nlm.nih.gov/26457764/ [2] http://mct.aacrjournals.org/content/8/12_Supplement/A244.short [3] http://cancerres.aacrjournals.org/content/75/15_Supplement/5390 [4] https://pubmed.ncbi.nlm.nih.gov/36101520/ [5] https://pubmed.ncbi.nlm.nih.gov/33229458/

Applikationer (Applications)

Metoder	Biomarkörer	Bilder	PMID
Western blot	Cyclin A1 / Cyclin E1 / p27 / p21 p-ALK / ALK / p-ERK / ERK / p-STAT3 / STAT3 pTrkA-Y490 / TrkA / p-PLCγ-Y783 / PLCγ pAKT / AKT		26735175
Growth inhibition assay	Cell viability		26172300

Klinisk prövningsinformation (Clinical Trial Information)

(data från https://clinicaltrials.gov, uppdaterad den 2024-05-22)

NCT-nummer	Rekrytering	Tillstånd	Sponsor/Samarbetspartners	Startdatum	Faser
NCT05770544	Recruiting	Solid Tumor\|Haematological Malignancy\|Malignancy\|Malignant Neoplasm\|Lymphoproliferative Disorders\|Neoplasms by Histologic Type\|Neoplasms by Site\|Cancer\|Brain Neoplasms\|Melanoma\|Glioma	Cancer Research UK\|University of Manchester\|University of Birmingham\|Royal Marsden NHS Foundation Trust\|Hoffmann-La Roche	June 2024	Phase 2\|Phase 3
NCT04551495	Recruiting	Invasive Lobular Breast Carcinoma\|ER+ Breast Cancer\|HER2-negative Breast Cancer	Jules Bordet Institute\|Hoffmann-La Roche	January 14 2021	Phase 2
NCT04226833	Completed	Hepatic Insufficiency	Hoffmann-La Roche	February 11 2020	Phase 1
NCT03796013	Completed	Healthy Volunteers	Genentech Inc.	January 10 2019	Phase 1

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

Entrectinib (Rxdx-101) Trk receptor Hämmare

Molekylvikt: 560.64

Kvalitetskontroll (Quality Control)

Cellodling, behandling & arbetskoncentration
(Cell Culture, Treatment & Working Concentration)

Kemisk information, lagring & stabilitet (Chemical Information, Storage & Stability)

Löslighet (Solubility)

Molaritetsräknare

In vivo-formuleringsräknare (Klar lösning)

Verkningsmekanism (Mechanism of Action)

Applikationer (Applications)

Klinisk prövningsinformation (Clinical Trial Information)

Entrectinib (Rxdx-101) Trk receptor Hämmare

Molekylvikt: 560.64

Kvalitetskontroll (Quality Control)

Cellodling, behandling & arbetskoncentration (Cell Culture, Treatment & Working Concentration)

Kemisk information, lagring & stabilitet (Chemical Information, Storage & Stability)

Löslighet (Solubility)

Molaritetsräknare

In vivo-formuleringsräknare (Klar lösning)

Verkningsmekanism (Mechanism of Action)

Applikationer (Applications)

Klinisk prövningsinformation (Clinical Trial Information)

Cellodling, behandling & arbetskoncentration
(Cell Culture, Treatment & Working Concentration)