Description

Product Description

Larotrectinib Sulfate (CAS 1223405-08-0) is a highly selective, orally bioavailable small-molecule inhibitor of tropomyosin receptor kinases TRKA, TRKB, and TRKC. These kinases, encoded by the NTRK1, NTRK2, and NTRK3 genes, are key oncogenic drivers in tumors harboring NTRK gene fusions. Larotrectinib has demonstrated profound anti-proliferative effects in preclinical models by blocking TRK-mediated signaling cascades, including MAPK/ERK, PI3K/AKT, and PLCγ pathways.

The solution formulation allows precise dosing for in vitro assays, xenograft models, and pharmacodynamic studies. This high-purity solution is particularly suitable for preclinical cancer research focused on NTRK fusion-positive cell lines, including solid tumors, sarcomas, and rare pediatric malignancies.

Chemical and Structural Features

Larotrectinib Sulfate is the sulfate salt form of Larotrectinib, enhancing aqueous solubility and stability. The molecular formula is C29H30ClN7O3S·H2SO4, with a molecular weight of 584.1 g/mol (sulfate salt). Structurally, it contains a pyrrolopyrimidine core linked to aromatic and heterocyclic groups, allowing high-affinity binding to the ATP-binding site of TRK kinases. This selectivity is crucial for minimizing off-target effects and maintaining potent inhibition of NTRK fusion-driven oncogenic pathways.

Pharmacological Significance

Larotrectinib Sulfate acts as a pan-TRK inhibitor with IC50 values in the low nanomolar range for TRKA, TRKB, and TRKC. By suppressing kinase activity, it prevents phosphorylation of downstream effectors such as MEK, ERK, PI3K, and AKT, ultimately leading to:

• Inhibition of cell proliferation and survival in NTRK fusion-positive cancer cells

• Induction of cell-cycle arrest, predominantly at G1/S phase

• Activation of intrinsic apoptotic pathways

• Suppression of tumor growth and angiogenesis in xenograft models

The Larotrectinib Sulfate compound has been extensively validated in vitro using NTRK fusion-positive cancer cell lines and in vivo using mouse xenograft models, demonstrating dose-dependent tumor regression, high selectivity, and manageable preclinical toxicity profiles.

Preclinical Applications

Larotrectinib Sulfate solution is particularly useful for:

• TRK Signaling Studies: Investigating TRKA/B/C kinase activity, downstream MAPK/ERK and PI3K/AKT pathways.

• NTRK Fusion Cancer Research: Exploring tumor dependency on NTRK fusions in solid tumors and sarcomas.

• Apoptosis and Cytotoxicity Studies: Evaluating intrinsic and extrinsic apoptotic pathways via caspase activation, mitochondrial depolarization, and ROS generation.

• Combination Therapy Studies: Testing synergy or antagonism with chemotherapy, targeted inhibitors, or immunotherapy in preclinical models.

• Resistance Mechanism Investigations: Studying acquired resistance through TRK kinase domain mutations, alternative signaling activation, or drug efflux modulation.

• Pharmacokinetic and Pharmacodynamic Evaluations: Using solution formulation for dose titration in in vivo studies and PK/PD modeling.

  

Product Specifications

Larotrectinib Sulfate Mechanism of Action

TRK Kinase Inhibition

Larotrectinib Sulfate selectively binds to the ATP-binding pocket of TRKA, TRKB, and TRKC kinases, preventing autophosphorylation and downstream signaling. Inhibition of TRK kinases blocks:

• MAPK/ERK pathway: Reduces proliferation and survival signals in tumor cells

• PI3K/AKT pathway: Promotes apoptosis and decreases cell viability

• PLCγ signaling: Modulates calcium-dependent signaling and cytoskeletal dynamics

Apoptosis Induction

• Mitochondrial depolarization and cytochrome c release

• Caspase-3 and caspase-9 activation

• ROS generation and oxidative stress contributing to cell death

• G1/S cell-cycle arrest in NTRK fusion-positive cells

Preclinical Research Applications

• Mechanistic studies in TRK fusion-positive cell lines

• Evaluation of tumor regression in xenograft models

• Combination therapy assays with chemotherapeutics or kinase inhibitors

• Resistance mechanism analysis, including kinase domain mutations and bypass pathway activation

  

Side Effects (Preclinical Observations)

Cellular Effects

• Reduced proliferation of TRK-driven cancer cells

• G1/S phase cell-cycle arrest

• ROS-mediated stress responses

• Modulation of intracellular signaling networks

Apoptotic Effects

• Activation of caspase-dependent intrinsic apoptotic pathways

• Mitochondrial depolarization

• p53-dependent and independent apoptosis

Laboratory Handling

• Handle with appropriate PPE in a fume hood

• Store at 2–8 °C, protect from light

• Avoid repeated freeze-thaw cycles

Larotrectinib Sulfate Follow institutional biosafety guidelines due to cytotoxic properties

Keywords

Larotrectinib Sulfate, LOXO-101 Sulfate, TRK inhibitor, TRKA inhibitor, TRKB inhibitor, TRKC inhibitor, NTRK fusion cancer research, angiogenesis studies, apoptosis research, cytotoxicity assays, preclinical oncology, high-purity research chemical, factory small-molecule supplier, China chemical manufacturer, OEM & bulk production, laboratory research reagent

Shipping Guarantee

All Larotrectinib Sulfate shipments of Larotrectinib Sulfate solution are handled with validated cold-chain logistics to ensure compound stability. Packages are sealed with secondary protective wrapping and shipped via express international couriers with tracking and insurance. Conditions are monitored to maintain solution integrity during transit.

Trade Assurance

We Larotrectinib Sulfate guarantee the authenticity and quality of all Larotrectinib Sulfate batches. Purity is verified at ≥99% via HPLC, MS, and NMR. Certificates of Analysis (CoA) are provided for each batch. Replacement or refund is assured for any deviation from listed specifications.

Payment Support

Larotrectinib Sulfate Flexible global payment options include:

• PayPal

• Major credit cards (Visa, MasterCard, American Express)

• Bank transfer (T/T)

• Cryptocurrencies (USDT, Bitcoin, Ethereum)

All Larotrectinib Sulfate transactions are encrypted to ensure security and confidentiality.

Disclaimer

Larotrectinib Sulfate is supplied strictly for laboratory research purposes. Not for human or veterinary use. Researchers must follow institutional safety and chemical handling protocols. Supplier assumes no liability for misuse.

References

• PubChem: Larotrectinib Sulfate (CID 46220546)

• ChEMBL: Larotrectinib Bioactivity Summary (CHEMBL3981132)

• DrugBank: Larotrectinib – DB14755

• PubMed: Larotrectinib Mechanism and Preclinical Studies (PMID 30773525)

• IUPHAR/BPS Guide to Pharmacology: TRK Inhibitors