PriceList for Atenolol Hydrochlorothiazide - LOXO-101 1223403-58-4 – CPF
PriceList for Atenolol Hydrochlorothiazide - LOXO-101 1223403-58-4 – CPF Detail:
IC50: low nanomolar range for inhibition of all TRK family members
LOXO-101 is a tropomyosin receptor kinases (TRK) inhibitor.
The TRK family of neurotrophin receptors and their neurotrophin ligands regulate neuron growth, differentiation and survival.
In vitro: In previous study, LOXO-101 was evaluated for off-target kinase enzyme inhibition against a panel of non-TRK kinases at a concentration of 1,000 nM and ATP concentrations around the Km. Results showed that LOXO-101 had greater than 50% inhibition for only one non-TRK kinase, which was TNK2 with IC50 of 576 nM. Moreover, there were neither relevant hERG inhibition nor prolonged QT observation .
In vivo: Animal study found that LOXO-101 was able to inhibit in vivo tumor growth. Athymic nude mice injected with KM12 cells were orally treated with LOXO-101 daily for 2 weeks, and dose-dependent tumor inhibition was observed, indicating the ability of LOXO-101 to inhibit in-vivo tumor growth .
Clinical trial: A multicenter phase I dose-escalation study in patients with advanced solid tumors (ClinicalTrials.gov no. NCT02122913) was conducted in 2014 to evaluate the safety and PK of LOXO-101. Patients are dosed once or twice daily for 28 days of continuous dosing in escalating cohorts. Preliminary PK and safety data indicate that the free plasma levels of LOXO-101 are at biologically relevant concentrations to inhibit TRK oncogenes. In this study, the first and only patient showed TRK fusion and the rapid clinical tumor regression seen with the treatment of LOXO-101 .
 Doebele RC et al. An Oncogenic NTRK Fusion in a Patient with Soft-Tissue Sarcoma with Response to the Tropomyosin-Related Kinase Inhibitor LOXO-101. Cancer Discov.2015 Oct;5(10):1049-57.
Larotrectinib (LOXO-101) is an ATP-competitive oral, selective inhibitor of the tropomyosin-related kinase (TRK) family receptors, with low nanomolar 50% inhibitory concentrations against all three isoforms (TRKA, B, and C).
|NCT Number||Sponsor||Condition||Start Date||
|NCT03025360||Bayer||Tumors Harboring NTRK Fusion||
|NCT02637687||Bayer||Solid Tumors Harboring NTRK Fusion||December 16, 2015||
Phase 1|Phase 2
|NCT02122913||Bayer||Solid Tumors Harboring NTRK Fusion||May 4, 2014||
|NCT03213704||National Cancer Institute (NCI)||Advanced Malignant Solid Neoplasm|Recurrent Ependymoma|Recurrent Ewing Sarcoma+Peripheral Primitive Neuroectodermal Tumor|Recurrent Glioma|Recurrent Hepatoblastoma|Recurrent Langerhans Cell Histiocytosis|Recurrent Malignant Germ Cell Tumor|Recurrent Malignant Glioma|Recurrent Malignant Solid Neoplasm|Recurrent Medulloblastoma|Recurrent Neuroblastoma|Recurrent Non-Hodgkin Lymphoma|Recurrent Osteosarcoma|Recurrent Rhabdoid Tumor|Recurrent Rhabdomyosarcoma|Recurrent Soft Tissue Sarcoma|Refractory Ependymoma|Refractory Ewing Sarcoma+Peripheral Primitive Neuroectodermal Tumor|Refractory Glioma|Refractory Hepatoblastoma|Refractory Langerhans Cell Histiocytosis|Refractory Malignant Germ Cell Tumor|Refractory Malignant Glioma|Refractory Malignant Solid Neoplasm|Refractory Neuroblastoma|Refractory Non-Hodgkin Lymphoma|Refractory Osteosarcoma|Refractory Primary Central Nervous System Neoplasm|Refractory Rhabdoid Tumor|Refractory Rhabdomyosarcoma|Wilms Tumor||July 24, 2017||
|NCT02465060||National Cancer Institute (NCI)||Advanced Malignant Solid Neoplasm|Bladder Carcinoma|Breast Carcinoma|Cervical Carcinoma|Colon Carcinoma|Colorectal Carcinoma|Endometrial Carcinoma|Esophageal Carcinoma|Gastric Carcinoma|Glioma|Head and Neck Carcinoma|Kidney Carcinoma|Liver and Intrahepatic Bile Duct Carcinoma|Lung Carcinoma|Lymphoma|Malignant Uterine Neoplasm|Melanoma|Ovarian Carcinoma|Pancreatic Carcinoma|Plasma Cell Myeloma|Prostate Carcinoma|Rectal Carcinoma|Recurrent Bladder Carcinoma|Recurrent Breast Carcinoma|Recurrent Cervical Carcinoma|Recurrent Colon Carcinoma|Recurrent Colorectal Carcinoma|Recurrent Esophageal Carcinoma|Recurrent Gastric Carcinoma|Recurrent Glioma|Recurrent Head and Neck Carcinoma|Recurrent Liver Carcinoma|Recurrent Lung Carcinoma|Recurrent Lymphoma|Recurrent Malignant Solid Neoplasm|Recurrent Melanoma|Recurrent Ovarian Carcinoma|Recurrent Pancreatic Carcinoma|Recurrent Plasma Cell Myeloma|Recurrent Prostate Carcinoma|Recurrent Rectal Carcinoma|Recurrent Skin Carcinoma|Recurrent Thyroid Gland Carcinoma|Recurrent Uterine Corpus Cancer|Refractory Lymphoma|Refractory Malignant Solid Neoplasm|Refractory Plasma Cell Myeloma|Skin Carcinoma|Thyroid Gland Carcinoma|Uterine Corpus Cancer||August 12, 2015||
|NCT03834961||Children´s Oncology Group|National Cancer Institute (NCI)||Central Nervous System Neoplasm|Infantile Fibrosarcoma|Recurrent Acute Leukemia|Refractory Acute Leukemia|Solid Neoplasm||September 18, 2019||
|NCT04142437||Bayer||Locally Advanced or Metastatic Solid Tumor Harboring an NTRK Gene Fusion||April 3, 2020||
|NCT03155620||National Cancer Institute (NCI)||Advanced Malignant Solid Neoplasm|Ann Arbor Stage III Non-Hodgkin Lymphoma|Ann Arbor Stage IV Non-Hodgkin Lymphoma|Histiocytic Sarcoma|Juvenile Xanthogranuloma|Langerhans Cell Histiocytosis|Malignant Glioma|Recurrent Childhood Rhabdomyosarcoma|Recurrent Ependymoma|Recurrent Ewing Sarcoma|Recurrent Glioma|Recurrent Hepatoblastoma|Recurrent Langerhans Cell Histiocytosis|Recurrent Malignant Germ Cell Tumor|Recurrent Malignant Solid Neoplasm|Recurrent Medulloblastoma|Recurrent Neuroblastoma|Recurrent Non-Hodgkin Lymphoma|Recurrent Osteosarcoma|Recurrent Peripheral Primitive Neuroectodermal Tumor|Recurrent Primary Central Nervous System Neoplasm|Recurrent Rhabdoid Tumor|Recurrent Soft Tissue Sarcoma|Refractory Ewing Sarcoma|Refractory Glioma|Refractory Hepatoblastoma|Refractory Langerhans Cell Histiocytosis|Refractory Malignant Germ Cell Tumor|Refractory Malignant Solid Neoplasm|Refractory Medulloblastoma|Refractory Neuroblastoma|Refractory Non-Hodgkin Lymphoma|Refractory Osteosarcoma|Refractory Peripheral Primitive Neuroectodermal Tumor|Refractory Primary Central Nervous System Neoplasm|Refractory Rhabdoid Tumor|Refractory Rhabdomyosarcoma|Rhabdoid Tumor|Stage III Osteosarcoma AJCC v7|Stage III Soft Tissue Sarcoma AJCC v7|Stage IV Osteosarcoma AJCC v7|Stage IV Soft Tissue Sarcoma AJCC v7|Stage IVA Osteosarcoma AJCC v7|Stage IVB Osteosarcoma AJCC v7|Wilms Tumor||July 24, 2017||
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