GLPBio

LOXO-101 (Larotrectinib) sulfate

Catalog No.: GC15282Purity:>99.50%
COASDSData Sheet
LOXO-101 (Larotrectinib) Sulfat (LOXO-101 Sulfat; ARRY-470 Sulfat) ist ein ATP-kompetitiver oraler, selektiver Inhibitor der Rezeptoren der Tropomyosin-Related Kinase (TRK)-Familie mit niedrigen nanomolaren 50 % Hemmkonzentrationen gegen alle drei Isoformen (TRKA, B und C).

Die Produkte sind ausschließlich für Forschungszwecke bestimmt. Nicht zur Anwendung am Menschen. Wir verkaufen nicht an Patienten.

LOXO-101 (Larotrectinib) sulfate
Cas No.: 1223405-08-0
10mM (in 1mL DMSO)In Stock
$46.00
1
5mgIn Stock
$40.00
1
10mgIn Stock
$62.00
1
25mgIn Stock
$119.00
1
50mgIn Stock
$197.00
1
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    618, 1017–1023 (2023)
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    610, 366–372 (2022)
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    187(9):2288-2304 (2024)
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    183(7):1867-1883 (2020)
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Beschreibung (Description)

LOXO-101 (Larotrectinib) sulfate is orally available, ATP-competitive pan-TRK inhibitor, with IC50 values of 0.9nM and 2.8nM for TRKA and TRKC, respectively [1]. LOXO-101 sulfate preferentially blocks the ATP-binding site of TRKA, TRKB, and TRKC, thereby inhibiting the TRK catalytic activity, the autophosphorylation, and the activation of downstream pathways [2]. LOXO-101 sulfate has been widely used in preclinical models to inhibit tumor growth[3].

In vitro, LOXO-101 sulfate treatment for 72 hours significantly inhibited the proliferation of CUTO-3.29 cells, KM12 cells and MO-91 cells, with IC50 values of 59nM, 3.5nM and 1nM, respectively[4]. Treatment with 300nM LOXO-101 sulfate for 24 hours significantly upregulated the expression of the epithelial marker E-cadherin in HCT116 cells, decreased the expression of mesenchymal markers (including vimentin and MMP2), and inhibited cell migration[5]. Treatment of T98G cells with 1μM LOXO-101 sulfate for 24 hours induced apoptosis, disrupted mitochondrial membrane potential and upregulated the activities of caspase 3, 8 and 9[6].

In vivo, LOXO-101 sulfate treatment via oral administration at a dose of 200mg/kg/day for 6 weeks significantly reduced the levels of leukemic infiltration in the bone marrow and spleen of the patient-derived xenograft (PDX) mouse model of ETV6-NTRK3 [7]. Oral administration of LOXO-101 sulfate (50mg/kg) three times a week for 5 weeks can significantly inhibit the growth of tumors in a 143B/NGF (overexpressed NGF) cell-xenograft mouse model, without affecting the weight of the mice[8].

References:
[1] Drilon A, Nagasubramanian R, Blake J F, et al. A next-generation TRK kinase inhibitor overcomes acquired resistance to prior TRK kinase inhibition in patients with TRK fusion–positive solid tumors[J]. Cancer discovery, 2017, 7(9): 963-972.
[2] Berger S, Martens U M, Bochum S. Larotrectinib (LOXO-101)[J]. Small Molecules in Oncology, 2018: 141-151.
[3] Hong D S, Brose M S, Doebele R C, et al. Abstract PR13: Clinical safety and activity from a phase 1 study of LOXO-101, a selective TRKA/B/C inhibitor, in solid-tumor patients with NTRK gene fusions[J]. Molecular Cancer Therapeutics, 2015, 14(12_Supplement_2): PR13-PR13.
[4] Doebele R C, Davis L E, Vaishnavi A, et al. An oncogenic NTRK fusion in a patient with soft-tissue sarcoma with response to the tropomyosin-related kinase inhibitor LOXO-101[J]. Cancer discovery, 2015, 5(10): 1049-1057.
[5] Kong W, Zhu H, Zheng S, et al. Larotrectinib induces autophagic cell death through AMPK/mTOR signalling in colon cancer[J]. Journal of cellular and molecular medicine, 2022, 26(21): 5539-5550.
[6] Zając A, Sumorek-Wiadro J, Maciejczyk A, et al. The engagement of Ras/Raf/MEK/ERK and PLCγ1/PKC pathways regulated by TrkB receptor in resistance of glioma cells to elimination upon apoptosis induction[J]. Neuropharmacology, 2025, 262: 110204.
[7] Roberts K G, Bridges O, Janke L J, et al. Genetic Modeling and Therapeutic Targeting of ETV6-NTRK3 with Loxo-101in Acute Lymphoblastic Leukemia[J]. Blood, 2016, 128(22): 278.
[8] Hou C H, Chen W L, Lin C Y. Targeting nerve growth factor-mediated osteosarcoma metastasis: mechanistic insights and therapeutic opportunities using larotrectinib[J]. Cell Death & Disease, 2024, 15(5): 381.

Protokoll (Protocol)

Cell experiment [1]:

Cell lines

KM12 cells

Preparation Method

KM12 cells were maintained in DMEM medium supplemented with, 100units/ml penicillin plus 100µg/ml streptomycin, and heat-inactivated fetal calf serums to a final concentration of 10% in humidified atmosphere with 5% CO2 at 37°C. Cells were seeded in 96-well plates at a density of 1000 cells per well. After 24h, cells were incubated in the presence of different concentrations of LOXO-101 sulfate (0, 1, 10, 100, 1000, and 10000nM), or the vehicle alone (DMSO) for 72h. Cell proliferation was measured.

Reaction Conditions

0, 1, 10, 100, 1000, and 10000nM; 72h

Applications

LOXO-101 sulfate treatment inhibited the cell viability of KM12 cells in a dose-dependent manner.
Animal experiment [2]:

Animal models

Male BALB/c nude mice

Preparation Method

Male BALB/c nude mice (4 weeks old, weighing 24±2g) were housed in an SPF animal facility with 12/12h light/dark cycle (25±1℃, humidity 60±10%), and fed with laboratory regular diet and sterilized water ad libitum. Under 1.5–2.5% isoflurane anesthesia, 5×106 143B/NGF cells were implanted into the right tibia of each mouse using a solution comprising 50% serum-free DMEM and 50% matrigel (total volume of 100μl). The mice in the 143B/NGF+LOXO-101 sulfate group were administered LOXO-101 sulfate (50mg/kg) orally three times a week for five weeks. Body weights and tumor volumes were assessed regularly.

Dosage form

50mg/kg; three times a week for five weeks; p.o.

Applications

LOXO-101 sulfate treatment significantly inhibited 143B/NGF tumor growth without affecting the body weight of the mice.

References:
[1] Doebele R C, Davis L E, Vaishnavi A, et al. An oncogenic NTRK fusion in a patient with soft-tissue sarcoma with response to the tropomyosin-related kinase inhibitor LOXO-101[J]. Cancer discovery, 2015, 5(10): 1049-1057.
[2] Hou C H, Chen W L, Lin C Y. Targeting nerve growth factor-mediated osteosarcoma metastasis: mechanistic insights and therapeutic opportunities using larotrectinib[J]. Cell Death & Disease, 2024, 15(5): 381.

Produktdokumente (Product Documents)

Purity:>99.50%Appearance:A solid
COASDSData Sheet

Chemische Eigenschaften (Chemical Properties)

CAS-Nr.
1223405-08-0
Chemischer Name
(S)-N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide sulfate
SMILES
O=S(O)(O)=O.O=C(N1C[C@@H](O)CC1)NC2=C3N=C(N4[C@@H](C5=CC(F)=CC=C5F)CCC4)C=CN3N=C2
Summenformel
C21H24F2N6O6S
Molekulargewicht
526.51
Löslichkeit
DMSO : 100mg/mL
Lagerung
Store at -20°C
Allgemeine Hinweise
Wählen Sie anhand der Löslichkeitsdaten des Produkts ein geeignetes Lösungsmittel. Aliquotieren Sie die Stammlösung nach der Herstellung, um wiederholte Gefrier-Auftau-Zyklen zu vermeiden.
Verwenden Sie Stammlösungen bei Lagerung bei -80°C innerhalb von 6 Monaten bzw. bei -20°C innerhalb von 1 Monat.
Zur Verbesserung der Löslichkeit das Röhrchen auf 37°C erwärmen und für eine angemessene Dauer beschallen.
Versandbedingungen
Evaluierungsmuster werden mit Kühlakkus versandt. Andere verfügbare Größen werden bei Raumtemperatur oder auf Anfrage mit Kühlakkus versandt.

Rechner (Calculators)Molarität / Verdünnung / Molekulargewicht / Einheitenumrechnung / In-vivo-Formulierung / Löslichkeit

g/mol

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