LOXO-101 1223403-58-4
Papa kāʻei kua
IC50: pae nanomolar haʻahaʻa no ka pāpā ʻana i nā lālā ʻohana TRK āpau
ʻO LOXO-101 kahi mea hoʻoiho tropicyosin kinases (TRK) mea kāohi.
ʻO kaʻohana TRK o nā mea loaʻa nā neurotrophin a me kā lākou mau ligands neurotrophin e hoʻoponopono i ka ulu ʻana o ka neuron, ka ʻokoʻa a me ke ola
In vitro: I ke aʻo ʻana ma mua, loiloi ʻia ʻo LOXO-101 no ka pāpā ʻana o ka ʻenima kinase i waho i ka pahuhopu o nā kinase non-TRK ma kahi kūmole o ka 1000 nM a me ka ATP no ka Km. Ua hōʻike ʻia nā hopena i loaʻa ʻo LOXO-101 i ʻoi aku ma mua o 50% kaohi no hoʻokahi non-TRK kinase, ʻo ia ʻo TNK2 me IC50 o 576 nM. Eia kekahi, ʻaʻohe pili kūpono hERG a i ʻole nānā QT hoʻolōʻihi ʻia [1].
In vivo: ʻIke ʻia ka ʻike holoholona i hiki i ka LOXO-101 ke kāohi i ka ulu ulu vivo. Ua mālama waha ʻia nā ʻiole nude Athymic me nā hunaola KM12 me LOXO-101 i kēlā me kēia lā no 2 mau pule, a ua mālama ʻia ke kaohi ʻana o ka tumo pili i ka lāʻau, e hōʻike ana i ka hiki o LOXO-101 ke kāohi i ka ulu ulu ulu vivo [1].
Hoʻokolohua hoʻokolohua: Ua mālama ʻia kahi mahele multicenter I i hoʻopaʻa ʻia i nā maʻi me nā tumors paʻa holomua (ClinicalTrials.gov no. NCT02122913) i ka makahiki 2014 e loiloi i ka palekana a me PK o LOXO-101. Hoʻokomo ʻia nā mea maʻi i hoʻokahi a i ʻole ʻelua mau lā i kēlā me kēia lā no 28 mau lā o ka hana mau ʻana i nā cohorts e piʻi nei. Hōʻike ka PK mua a me ka ʻikepili palekana i nā pae plasma manuahi o LOXO-101 ma nā kikoʻī e pili ana i ka biologically e kāohi i nā oncogenes TRK. I kēia noi ʻana, ua hōʻike ka mea maʻi mua a hoʻokahi wale nō TRK fusion a me ka wikiwiki o ke kūpikipiki maʻi ʻōniu i ʻike ʻia me ka mālama ʻana iā LOXO-101 [1].
Kuhikuhi:
[1] Doebele RC et al. ʻO kahi Oncogenic NTRK Fusion i kahi mea maʻi me ka Sarcoma Soft-Tissue me ka pane i ka Tropomyosin-pili Kinase Inhibitor LOXO-101. Cancer Discov. 2015 ʻOkakopa; 5 (10): 1049-57.
Wehewehe
ʻO Larotrectinib (LOXO-101) he mea hoʻokūkū waha ATP, mea hōʻoki koho o nā kinase ʻohana e pili ana i ka tropomyosin (TRK), me nā nanomolar haʻahaʻa 50% hoʻoikaika kūwaho e kūʻē i nā isoforms ʻekolu (TRKA, B, a me C).
Hoʻokolohua Lapaʻau
Helu NCT | Kākoʻo | Kūlana | Lā Hoʻomaka |
ʻĀpana |
NCT03025360 | Bayer | Tumors Harboring NTRK Hoʻohui |
|
|
NCT02637687 | Bayer | Pākuʻi Tumors Harbour NTRK Fusion | Kekemapa 16, 2015 |
Papa 1 | Papa 2 |
NCT02122913 | Bayer | Pākuʻi Tumors Harbour NTRK Fusion | 4 Mei 2014 |
Papa 1 |
NCT03213704 | Ke Keʻena Luna ʻInikena National (NCI) | ʻO Neoplasm Mākaʻi Mākaʻikaʻi Advanced | Ependymoma Kūʻai Hou | Ewing Sarcoma + Peripheral Primitive Neuroectodermal Tumor | ʻO Glioma hou | Hepatoblastoma hou | Recurrent Langerhans Cell Histiocytosis | Hoʻohui Malignant Germ Cell Tumor | Recurrent Malignant Grooma | Recopent Malignant | Non-Hodgkin Lymphoma | ʻO ka hou Osteosarcoma | ʻO Rhabdoid Tumor kū hou | ʻO Rhabdomyosarcoma kū hou | ʻO Recomment Soft Tissue Sarcoma | Refractory Ependymoma | Refractory Ewing Sarcoma + Peripheral Primitive Neuroectodermal Tumor | Refractory Glioma Reactory 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 | Lulai 24, 2017 |
Kau 2 |
NCT02465060 | Ke Keʻena Luna ʻInikena National (NCI) | ʻO Advanced Neignlas Solid Neoplasm | ʻO ka maʻi ʻaʻai | ʻO ka maʻi kanulau | ʻO ka maʻi maʻi | ʻOihana kāne | ʻO ka maʻi maʻi maʻi | Endometrial Carcinoma | ʻO Esophageal Carcinoma | ʻO Gastric Carcinoma | Glioma | ʻO ke poʻo poʻo a me ka ʻāʻī maʻi | Ka maʻi kīhāhā | Līkū pūhū | Malignant Uterine Neoplasm | Melanoma | Ovarian Carcinoma | Pancreatic Car cancer | Kāleka Glioma | Ke poʻo hou a me ka maʻi kanikau | Ka maʻi kanesa kū hou | Ka maʻi ʻaʻa maʻi | Lymphoma kū hou | Ka neʻe hou malignant neoplasm | Melanoma kū hou | Ka maʻi kanesa Ovarian | Ka maʻi kanesa hou | Ka maʻi kanesa maʻi | | ʻO ka maʻi kanesa o ka ʻili hou | Kelepona thyroid hou Ka maʻi ʻaʻai | Ka maʻi ʻaʻai Uterine Corpus maʻi ʻaʻai | Refractory Lymphoma | Refractory Malignant Solid Neoplasm | Refractory Plasma Cell Myeloma | ʻIli maʻi ʻaʻai | ʻO ka thyroid gland carcinoma | kōpū maʻi ʻōpū | ʻAukake 12, 2015 |
Kau 2 |
NCT03834961 | ʻOihana Oncology Children | National Cancer Institute (NCI) | ʻO Neoplasm Pūnaewele Nervous Waena | Fibrosarcoma Infantile | Leukemia Acute Hou | ʻO Leukemia Refractory Acute | Neoplasm paʻa | Kepakemapa 18, 2019 |
Kau 2 |
NCT04142437 | Bayer | ʻO ka pae kiʻekiʻe a i ʻole Metastatic Solid Tumor Harbouring a NTRK Gene Fusion | ʻApelila 3, 2020 |
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NCT03155620 | Ke Keʻena Luna ʻInikena National (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 Epoma ʻO Hepatoblastoma hou hou | ʻO Langerhans Cell Histiocytosis Pūnaewele | ʻO ka Neoplasm Maʻemaʻe Malignant | Kūleʻa Malignant Solid Neoplasm | ʻO Medulloblastoma hou | ʻO Neuroblastoma hou | ʻO Non-Hodgkin Lymphoma | ʻO Osteosarcoma Pūnaewele Nūhou Neuro | | ʻO Recomment 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 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 Osteoscomue | Kahua IVA Osteosarcoma AJCC v7 | kahua IVB Osteosarcoma AJCC v7 | Wilms Tumor | Lulai 24, 2017 |
Kau 2 |
ʻAno kemika
Palapala Noi 18 Nā papahana loiloi e like me ka Consistency i ʻae ʻia 4, a 6 ke ʻae ʻia nei nā papahana.
Ua hoʻokumu ʻia ka ʻōnaehana hoʻokele kūlana kiʻekiʻe kiʻekiʻe loa no ke kūʻai aku.
Holo ka nānā ʻana i ka maikaʻi ma waena o ke ola holoʻokoʻa o ka huahana e hōʻoia i ka maikaʻi a me ka hopena therapeutic.
Kākoʻo ka ʻoihana Hoʻokele ʻoihana ʻoihana i nā koi maikaʻi i ka wā o ka noi a me ke kau inoa.