Haina LOXO-101 1223403-58-4 kaihanga me nga kaihoko

LOXO-101 1223403-58-4

Whakaahuatanga Poto:

Ingoa o API	Tohu	Kaiwhiwhi	Te Ra Paunga o te Patent (Te US)
LOXO-101 1223403-58-4	Tarukino Oncology	Loxo Oncology	Oketopa 21,2029

Tukuna imeera ki a maatau

Taipitopito Hua

Tohu Hua

WHAKAWEHE KOREUTU

Papamuri

IC50: awhe nanomolar iti hei aukati i nga mema katoa o te whanau TRK

Ko te LOXO-101 he kaiwhakawhiwhi i te kaikohi tropicyosin kinases (TRK) hei aukati.

Ko te whanau TRK o nga kaiwhakawhiwhi neurotrophin me a ratau hononga neurotrophin e whakahaere ana i te tipu o te neuron, te rereketanga me te oranga.

I roto i te vitro: I roto i nga rangahau o mua, i arotakehia a LOXO-101 mo te aukati i te wharoke a te kinase kore ki te papa o nga kinase kore-TRK i te kukume o te 1,000 nM me te ATP kukū huri noa i te Km. I whakaatuhia nga kitenga ko te LOXO-101 he nui ake i te 50% aukati mo te kotahi noa ehara i te TRK kinase, ko te TNK2 me te IC50 o te 576 nM. Ano hoki, kaore he kaupapa aukati i te HERG kaore ano kia roa te kitenga o te QT [1].

In vivo: I kitea e te rangahau kararehe ka taea e LOXO-101 te aukati i te tipu puku puku. Ko nga kiore tahanga o Athymic i werohia ki nga pūtau KM12 i rongohia-waha ki a LOXO-101 ia ra mo nga wiki e 2, a i kitea te aukati i te puku tumo-tiimata, e tohu ana i te kaha o te LOXO-101 ki te aukati i te tipu puku puku-vivo [1].

Whakamatau Haumanu: Ko te waahanga maha-maha o te rangahau horopeta-whakaniko i nga tuuroro me nga pukupuku pakari o mua (ClinicalTrials.gov nama. NCT02122913) i whakahaerehia i te 2014 hei arotake i te ahuru me te PK o LOXO-101. Ko nga tuuroro ka tutuki i te wa e rua ranei i ia ra mo nga ra 28 o te tohatoha haere tonu i roto i nga roopu piki haere. Ko te timatanga PK me nga raraunga haumaru e tohu ana ko nga taumata plasma koreutu o LOXO-101 kei nga waahanga koiora e haangai ana ki te aukati i nga oncogenes TRK. I roto i tenei rangahau, ko te manawanui tuatahi me te kotahi noa i whakaatu i te TRK honohono me te tere o te puku pukupuku haumanu kua kitea me te maimoatanga o LOXO-101 [1].

Tohutoro:
[1] Doebele RC et al. He Oncogenic NTRK Fusion i roto i te Tuuroro me te Hara-Koura Sarcoma me te Whakautu ki te Kaihaututu Kinase e Pa ana ki te Tropomyosin LOXO-101. Discov Mate Mate. 2015 Oketopa; 5 (10): 1049-57.

Whakaahuatanga

Larotrectinib (LOXO-101) he ATP-whakataetae waha, aukati whiriwhiri i nga kaiwhakawhiwhi o te whanau kinase (TRK) e pa ana ki te tropomyosin, me te iti o te nanomolar 50% te aukati i nga whakaahurutanga katoa ki nga isoform e toru (TRKA, B, me C)

Whakamatau Haumanu

Tau NCT	Kaitautoko	Tikanga	Ra Timata	Wāhanga
NCT03025360	Bayer	Tumors Harbouring NTRK Fusion
NCT02637687	Bayer	Nga Tumoro Tuturu Te Whakauru NTRK Fusion	Tihema 16, 2015	Wahanga 1 \| Wahanga 2
NCT02122913	Bayer	Nga Tumoro Tuturu Te Whakauru NTRK Fusion	Mei 4, 2014	Wahanga 1
NCT03213704	National Cancer Institute (NCI)	Neoplasm Mārō Mārō Atu Anō \| Ependymoma Huringa \| Huringa Ewing Sarcoma + Waahi Neuroectodermal Tumine Takitahi \| Taapara Glioma \| Hepatoblastoma Auau \| Tuarua Langerhans Cell Histiocytosis \| Taapiripiri Maapuku Tumutahi \| Puku Maamaa Kore Non-Hodgkin Lymphoma \| Osteosarcoma Recurrent \| Tumutu Rhabdoid \| Recurrent Rhabdomyosarcoma \| Recomment Soft Tissue Sarcoma \| Refractory Ependymoma \| Refractory Ewing Sarcoma + Peripheral Primitive Neuroectodermal Tumor \| Refractory Grefractory Refractory Glioma Malignant \| Refractory Malignant Solid Neoplasm \| Refractory Neuroblastoma \| Refractory Non-Hodgkin Lymphoma \| Refractory Osteosarcoma \| Refractory Kura Tuatahi Nervous System Neoplasm \| Refractory Rhabdoid Tumor \| Refractory Rhabdomyosarcoma \| Wilms Tumor	Hurae 24, 2017	Wahanga 2
NCT02465060	National Cancer Institute (NCI)	He Neoplasma Maataha Tino Maamaa \| Paa Mate Mate Uru \| Waa Kanui \| Whiu Waahi Tuuturu \| Tuku Mate Taha \| Waahorangi Tauhokohoko \| Waimarie Endometrial \| Waa Hakinakina \| Waimarie Hauhau \| Waimarie \| Pouaka Poutu me te Kiwi \| Waimarie Tinana \| Hinengaro Mate ate \| Malignant Uterine Neoplasm \| Melanoma \| Ovarian Carcinoma \| Pancreatic Carcinoma \| Plasma Cell Myeloma \| Carcinoma Prostate \| Huaketo Rectal \| Carcoma Uru Uru \| Waa Kanui Huringa \| Waa Huringa Haurangi \| Glioma Auau \| Taauru Tuarua me te Taha Kaha \| Mate Whiwhi Hainamana \| Kaahuahua Lung Carcinoma \| Lymphoma Huringa \| Neoplasma Maataha Maatahi \| Melanoma Huringa \| Huringa Okioki Ovarian \| Waimarie Hukapuku Huringa \| Waa Huringa Huringa Te Taakapa o te Kiri Hokiwaa \| Paa Taakaro Taa Carcinoma \| Mate Uru Korerotia Uterine \| Refractory Lymphoma \| Refractory Malignant Solid Neoplasm \| Refractory Plasma Cell Myeloma \| Taakaro Whaaiao \| Taakaro Koura Taakiko \| Mate Mate Mate Tuuwhenua	Akuhata 12, 2015	Wahanga 2
NCT03834961	Ropu Oncology Tamariki \| National Cancer Institute (NCI)	Neoplasm Pūnaha Nervous Central \| Fibrosarcoma Infantile \| Leukemia Puta Auahi \| Te Leukemia Mate Refractory \| Neoplasm Maama	Mahuru 18, 2019	Wahanga 2
NCT04142437	Bayer	Ko te Tumor o te Motu, o te Metastatic Tumor / Tumor ranei e mau ana i te NTRK Gene Fusion	Paenga-whāwhā 3, 2020
NCT03155620	National Cancer Institute (NCI)	Neoplasma Maaro Tino Maaro \| Ann Arbor Stage III Non-Hodgkin Lymphoma \| Ann Arbor Stage IV Non-Hodgkin Lymphoma \| Histcomcytic Sarcoma \| Juvenile Xanthogranuloma \| Langerhans Cell Histiocytosis \| Malignant Glioma \| Huringa Tamariki Rhabdomyosarcoma \| Recurrent Ependymoma Hepatoblastoma auau \| Haurangi Langerhans Cell Histiocytosis \| Huringa Malignant Maaka Puku Puku \| Huringa Malignant Maakiri Neoplasm \| Huringa Medulloblastoma \| Neuroblastoma Haurangi \| Haurangi Kore-Hodgkin Lymphoma \| Huringa Osteosarcoma \| Sarcoma Tissue ngohengohe toutouu \| 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 Paraimere Central Nervous System Neoplasm \| Refractory Rhabdoid Tumor \| Refractory Rhabdomyosarcoma \| Rhabdoid Tumor \| Atamira III Osteosarcoma AJCC v7 \| Atamira III Taapiri Tissue Sarcoma AJCC v7 \| Atamira IV Osteosarc \| Atamira IVA Osteosarcoma AJCC v7 \| Atamira IVB Osteosarcoma AJCC v7 \| Wilms Tumor	Hurae 24, 2017	Wahanga 2