GLPBio

LOXO-101 (Larotrectinib) sulfate

Catalog No.: GC15282Purity:>99.50%
COASDSData Sheet
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.

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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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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.

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.

Product Documents

Purity:>99.50%Appearance:A solid
COASDSData Sheet

Chemical Properties

CAS No.
1223405-08-0
Chemical 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
Molecular Formula
C21H24F2N6O6S
Molecular Weight
526.51
Solubility
DMSO : 100mg/mL
Storage
Store at -20°C
General tips
Select a suitable solvent according to the product solubility data. Once prepared, aliquot the stock solution to avoid repeated freeze-thaw cycles.
Use stock solutions within 6 months when stored at -80°C or within 1 month when stored at -20°C.
To improve solubility, warm the tube to 37°C and sonicate it for an appropriate period.
Shipping Condition
Evaluation samples are shipped with blue ice. Other available sizes are shipped at room temperature or with blue ice upon request.

CalculatorsMolarity / Dilution / Molecular Weight / Unit Conversion / In Vivo Formulation / Solubility

g/mol

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