Saina LOXO-101 1223403-58-4 gaosi oloa ma tagata sapalai

LOXO-101 1223403-58-4

Faʻamatalaga puʻupuʻu:

Igoa ole API	Faailoga	Tagata fou	Pateni Aso Uma (Le US)
LOXO-101 1223403-58-4	Vailaʻau oncology	Loxo Oncology	Oketopa 21,2029

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Oloa Faʻamatalaga

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Talaʻaga

IC50: maualalo nanomolar laina mo le taofiofia o TRK uma tagata o le aiga

LOXO-101 o se tropomyosin receptor kinases (TRK) taofi.

O le TRK aiga o neurotrophin talimalo talimalo ma latou neurotrophin ligands faʻatonutonu tuputupu ae neuron, eseesega ma ola.

In vitro: I le suʻesuʻega talu ai, LOXO-101 na iloiloina mo le faʻamutaina o le kinase enzyme taofiofi faasaga i le vaega o le non-TRK kinase i le faʻatauaina o 1,000 nM ma ATP faʻasologa faʻataʻamilomilo le Km. O iʻuga na faʻaalia ai o LOXO-101 na sili atu i le 50% taofi mo naʻo le tasi le TRK kinase, o le TNK2 ma le IC50 o le 576 nM. E le gata i lea, e leai se fesoʻotaʻiga talafeagai hERG poʻo le faʻaumiumi QT mataʻituina [1].

In vivo: O suesuega a manu na maua ai e le LOXO-101 na mafai ona taofia le tuputupu aʻe o le tuma o le vivo. O isumu ninii ole Athymic na tuiina ile sela o le KM12 na togafiti tuʻufofoga ma LOXO-101 i aso uma mo le 2 vaiaso, ma na vaʻaia le faʻatupulaia ole tumo e faʻalagolago ile tui, e faʻailoa mai ai le mafaia e LOXO-101 ona taofia le tuputupu aʻe ole tuma i totonu [1].

Faʻataʻitaʻiga faʻataʻitaʻi: O le multicenter phase I fualaʻau-faʻateleina suʻesuʻega i tagata mamaʻi ma le alualu i luma tuma (ClinicalTrials.gov Nu. NCT02122913) na faia i le 2014 e iloilo ai le saogalemu ma PK o LOXO-101. Tagata gasegase e faia faʻatasi pe faʻalua i aso uma mo le 28 aso o le faʻaauau pea i le faʻateleina o kulupu. Faʻamatalaga muamua PK ma le saogalemu faʻamatalaga faʻailoa mai o le maua fua o le plasma tulaga o le LOXO-101 o loʻo i mea faʻapitoa fesoʻotaʻiga faʻapitoa e taofia ai TRK oncogenes. I lenei suʻesuʻega, o le muamua ma naʻo le tagata maʻi na faʻaalia le TRK fusion ma le vave o le falemaʻi tumo faʻafuaseʻi vaaia ma le togafitiga o LOXO-101 [1].

Tusitusiga:
[1] Doebele RC et al. O le Oncogenic NTRK Fusion i le Tagata Onosaʻi ma le Soft-Tissue Sarcoma ma le Tali atu i le Tropomyosin-related Kinase Inhibitor LOXO-101. Kanesa Discov.2015 Oketopa; 5 (10): 1049-57.

Faʻamatalaga

Larotrectinib (LOXO-101) o se ATP-tauvaga tautala, filifilia filifili o le tropomyosin-related kinase (TRK) aiga mauaina, ma maualalo nanomolar 50% taofiofia taofi faasaga i uma tolu isoforms (TRKA, B, ma C).

Tofotofoina le Falemai

Numera NCT	Lagolago	Tulaga	Aso amata	Vaega
NCT03025360	Bayer	Tumors Harbouring NTRK Fusion
NCT02637687	Bayer	Solid Tumors Harbouring NTRK Fusion	Tesema 16, 2015	Vaega 1 \| Vaega 2
NCT02122913	Bayer	Solid Tumors Harbouring NTRK Fusion	Me 4, 2014	Vaega 1
NCT03213704	National Cancer Institute (NCI)	Advanced Malignant Solid Neoplasm \| Ependymoma Toe \| Faʻafuaseʻi Ewing Sarcoma + Peripheral Primitive Neuroectodermal Tumor \| Reclient Glioma \| Faʻaaoga Hepatoblastoma \| Recurrent Langerhans Cell Histiocytosis \| Recurrent Malignant Germ Cell Tumor \| Recurrent Malignant Gorrant \| Reopent Malignant Non-Hodgkin Lymphoma \| Osteosarcoma Toe Faʻafuaseʻi \| Toe Faʻafuaseʻi Rhabdoid \| Faʻasolosolo Rhabdomyosarcoma \| Toe Faʻafofilemu Filifili Sarcoma \| Refractory Ependymoma \| Refractory Ewing Sarcoma + Peripheral Primitive Neuroectodermal Tumor \| Refractory Refractory Refractory 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	Iulai 24, 2017	Vaega 2
NCT02465060	National Cancer Institute (NCI)	Advanced Malignant Solid Neoplasm \| Carbéroma o le susu \| Pepe o le kanesa \| Cervical Carcinoma \| Colon Carcinoma \| Colorectal Carcinoma \| Endometrial Carcinoma \| Esophageal Carcinoma \| Gastric Carcinoma \| Glioma \| Head and Neck Carcinoma \| Fatugaʻa o le Tino \| Loma kanesa \| Loma Kanesa \| Malignant Uterine Neoplasm \| Melanoma \| Ovarian Carcinoma \| Pancreatic Carcinoma \| Plasma Cell Myeloma \| O le Carostoma Carostoma \| Tafaʻi Glioma \| Tafaʻi Toe ma le ua o le kanesa \| Taʻua o le ate o le fatu \| Toe maua o le mama i le va Paʻu Paʻu Kanesa Faʻafu Carcinoma \| Kanesa Uterine Corpus Kanesa \| Refractory Lymphoma \| Refractory Malignant Solid Neoplasm \| Refractory Plasma Cell Myeloma \| Paʻu Carcinoma \| Thyroid Gland Carcinoma \| Uterine Corpus Kanesa	Aukuso 12, 2015	Vaega 2
NCT03834961	Tamaiti Oncology Group \| National Cancer Institute (NCI)	Neoplasm Neervlasm Central System	Setema 18, 2019	Vaega 2
NCT04142437	Bayer	Lotoifale alualu i luma poʻo Metastatic Solid Tumor Harbouring a NTRK Gene Fusion	Aperila 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 Goma \| Recurrent Ependymoma Hepatoblastoma toe tupu \| Faʻafuaseʻi Langerhans Cell Histiocytosis \| Toe oso Malignant Siama sela Tumau \| Faʻafuaseʻi Malignant mautu Neoplasm \| Faʻafitauli Medulloblastoma \| Faʻaaoga Neuroblastoma \| Faʻaaoga Non-Hodgkin Lymphoma \| Faʻaopoopo Osteosarcoma \| Faʻaaoga Peripheral Tumua Neuro \| Toe Faʻamalulu Filemu Sarcoma \| Refractory Ewing Sarcoma \| Refractory Glioma \| Refractory Hepatoblastoma \| Refractory Langerhans Cell Histiocytosis \| Refractory Malignant Germ Cell Tumor \| Refractory Malignant Solid Neoplasm \| Refractory Medulloblastoma \| Refractory Refractory ctory 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 Osteosisses \| Vaega IVA Osteosarcoma AJCC v7 \| Vaega IVB Osteosarcoma AJCC v7 \| Wilms Tumor	Iulai 24, 2017	Vaega 2