China LOXO-101 1223403-58-4 ndị na-emepụta ihe na ndị na-enye ngwaahịa

LOXO-101 1223403-58-4

Nkọwa nkenke:

Aha API	Ngosipụta	Onye mmepụta ihe	Patent Expbọchị mmebi (US)
LOXO-101 1223403-58-4	Oncology ọgwụ	Loxo Oncology	Ọkt 21,2029

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IC50: ala nanomolar di ala maka igbochi ndi TRK nile

LOXO-101 bụ onye na-emechi ihe na-eme ka ihe na-eme ihe ike (TRK).

Ezinụlọ TRK nke ndị nabatara neurotrophin na njikọ ha na-ahụ maka ntanetị na-achịkwa uto neuron, ọdịiche na nlanarị.

In vitro: Na ọmụmụ ihe gara aga, a na-enyocha LOXO-101 maka mgbochi enzyme kinase lekwasịrị anya na ngalaba nke ndị na-abụghị TRK kinases na mgbatị nke 1,000 nM na uche ATP gburugburu Km. Nsonaazụ gosiri na LOXO-101 nwere ihe karịrị 50% mgbochi maka naanị otu onye na-abụghị TRK kinase, nke bụ TNK2 na IC50 nke 576 nM. Ọzọkwa, enweghị mgbochi ọ bụla ma ọ bụ nchọpụta QT dị ogologo [1].

Na ndụ: Nnyocha nke anụmanụ chọpụtara na LOXO-101 nwere ike igbochi uto tumo na vivo. A na-eji ọnụ ekwu okwu na ụmụ irighiri agba ọtọ na-agba ume na mkpụrụ ndụ KM12 na LOXO-101 kwa ụbọchị maka izu 2, a na-ahụkwa mgbochi ọgwụ na-adabere na dose, na-egosi ike nke LOXO-101 iji gbochie uto tumo-vivo [1].

Ọnwụnwa ahụike: A na-eme nchọpụta ọmụmụ na-arịwanye elu nke ọtụtụ ndị ọrịa nwere akpụ siri ike (ClinicalTrials.gov no. NCT02122913) na 2014 iji nyochaa nchekwa na PK nke LOXO-101. A na-agwọ ndị ọrịa otu ugboro ma ọ bụ ugboro abụọ kwa ụbọchị maka ụbọchị iri abụọ na abụọ nke na-aga n’ihu na-arị elu. Oge mbụ PK na nchekwa data na-egosi na ọkwa plasma n'efu nke LOXO-101 nọ na ntanetị dị mkpa iji gbochie TRK oncogenes. N'ime ọmụmụ ihe a, onye mbụ nwere naanị ndidi gosipụtara njikọta TRK na ngwangwa ngwa ngwa na-ahụ maka ọgwụgwọ nke LOXO-101 [1].

Ntughari:
[1] Doebele RC et al. Oncogenic NTRK Fusion na Onye Ndidi na Soft-Tissue Sarcoma nwere Nzaghachi na Kinrop Inhibitor Tropomyosin metụtara LOXO-101. Ọrịa Cancer. 2015 Ọkt; 5 (10): 1049-57.

Nkọwa

Larotrectinib (LOXO-101) bụ onye na-asọ asọmpi ATP, onye na-emechi ihe nchịkwa nke ndị na-anabata ezinụlọ kinase (TRK) nke tropomyosin, na-enwe obere ihe na-egbochi 50% na-egbochi ihe mgbochi atọ (TRKA, B, na C).

Ọnwụnwa nyocha

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NCT03155620	National Cancer Institute (NCI)	Nnukwu Neoplasm siri ike \| Ann Arbor Stage III nke na-abụghị Hodgkin Lymphoma \| Ann Arbor Stage IV Non-Hodgkin Lymphoma \| Sarcoma Histiocytic \| Juvenile Xanthogranuloma \| Langerhans Cell Histiocytosis \| Ọrịa Glioma \| Ntanye urrentmụaka Rhabdomyosarcoma \| Ntugharị Ejegharị \| Ntughari Hepatoblastoma ugboro ugboro \| Ntighari Langerhans Cell Histiocytosis \| Ntighari Malignant Germ Cell Tumor \| Ntighari Malignant Solid Neoplasm \| Ntughari Medulloblastoma \| Ntughari Neuroblastoma \| Ntughari-non-Hodgkin Lymphoma \| Ntughari Osteosarcoma \| Ntugharị Peripheral Primitive Neuroectodum Tromorum \| Issudị anụ ahụ na-agagharị agagharị Sarcoma \| Refractory Ewing Sarcoma \| Refractory Glioma \| Refractory Hepatoblastoma \| Refractory Langerhans Cell Histiocytosis \| Refractory Ọrịa Germ Tumor Na-adịghị Mma \| Ọrịa Na-adịghị Mma Ọkpụkpụ \| Refractory Medulloblastoma \| Ọrịa Neuroblastoma Refractory \| ctory Peripheral Primitive Neuroectodermal Tumor \| Refractory Primary Central Nervous System Neoplasm \| Refractory Rhabdoid Tumor \| Refractory Rhabdomyosarcoma \| Rhabdoid Tumor \| Oge III Osteosarcoma AJCC v7 \| Stage III Soft Tissue Sarcoma AJCC v7 \| nkeji III \| Nkeji IVA Osteosarcoma AJCC v7 \| Nkeji IVB Osteosarcoma AJCC v7 \| Wilms Tumor	Ọnwa Asaa 24, 2017	Oge 2