Kina LOXO-101 1223403-58-4 nā mea hana a me nā mea hoʻolako

LOXO-101 1223403-58-4

Hōʻike Pōkole:

Ka inoa o API	Hōʻike	Mea Hoʻohou Hou	Palapala Hoʻoholo Patent (The US)
LOXO-101 1223403-58-4	Laau ʻona Oncology	Loxo Oncology	ʻOkakopa 21,2029

E hoʻouna leka uila iā mākou

ʻIke kikoʻī

Nā huahana huahana

ʻIkepili Huahana

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

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