China LOXO-101 1223403-58-4 awọn olupese ati awọn olupese

LOXO-101 1223403-58-4

Apejuwe Kukuru:

Orukọ API	Itọkasi	Onitumọ	Ọjọ Itọsi Itọsi (AMẸRIKA)
LOXO-101 1223403-58-4	Onkoloji oogun	Loxo Onkoloji	Oṣu Kẹwa. 21,2029

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Lẹhin

IC50: ibiti nanomolar kekere fun ihamọ gbogbo awọn ọmọ ẹbi TRK

LOXO-101 jẹ onidena olugba olugba olugba pupọ (TRK).

Idile TRK ti awọn olugba iṣan neurotrophin ati awọn ligand wọn ti neurotrophin ṣe itọsọna idagba neuron, iyatọ ati iwalaaye.

In vitro: Ninu iwadi iṣaaju, LOXO-101 ni a ṣe ayẹwo fun idena imukuro enzymu ti kii-fojusi lodi si nronu ti kii-TRK kinases ni ifọkansi ti 1,000 nM ati awọn ifọkansi ATP ni ayika Km. Awọn abajade fihan pe LOXO-101 ti ni idena pupọ ju 50% fun ọkan ti kii ṣe TRK kinase, eyiti o jẹ TNK2 pẹlu IC50 ti 576 nM. Pẹlupẹlu, ko si idena hERG ti o yẹ tabi akiyesi QT gigun [1].

Ni vivo: Iwadi eranko ri pe LOXO-101 ni anfani lati dojuti idagba tumo ara vivo. Awọn eku ihoho Athymic ti a fi abẹrẹ pẹlu awọn sẹẹli KM12 ṣe itọju ni ẹnu pẹlu LOXO-101 lojoojumọ fun awọn ọsẹ 2, ati pe a ṣe akiyesi idena ti o da lori iwọn lilo, ti o tọka agbara ti LOXO-101 lati dẹkun idagbasoke idagbasoke-in vivo [1].

Iwadii ile-iwosan: Ikẹkọ imunadoko iwọn lilo multicenter I I Study-escalation ni awọn alaisan ti o ni awọn èèmọ to ti ni ilọsiwaju (ClinicalTrials.gov No. A gba awọn alaisan ni ẹẹkan tabi lẹmeji lojoojumọ fun awọn ọjọ 28 ti dosing lemọlemọfún ni awọn olukọni ti n pọ si. Alakoko PK ati data aabo tọka pe awọn ipele pilasima ọfẹ ti LOXO-101 wa ni awọn ifọkansi ti o baamu nipa ẹda lati dojuti awọn oncogenes TRK. Ninu iwadi yii, alaisan akọkọ ati alaisan nikan ṣe afihan idapọ TRK ati ifasẹyin tumọ tumo si iyara ti a rii pẹlu itọju LOXO-101 [1].

Itọkasi:
[1] Doebele RC et al. An Fusion Oncogenic NTRK ni Alaisan pẹlu Soft-Tissue Sarcoma pẹlu Idahun si Olutọju Kinase ibatan ibatan Tropomyosin LOXO-101. Aarun Aarun .2015 Oṣu Kẹwa; 5 (10): 1049-57.

Apejuwe

Larotrectinib (LOXO-101) jẹ ẹnu ifigagbaga ATP kan, oluṣayan yiyan ti awọn olugba ẹbi ti ibatan ibatan ti tropomyosin (TRK), pẹlu awọn ifọkansi ifunni 50% nanomolar kekere si gbogbo awọn isoform mẹta (TRKA, B, ati C).

Iwadii Iwosan

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