China LOXO-101 1223403-58-4 opanga ndi ogulitsa

LOXO-101 1223403-58-4

Kufotokozera Kwachidule:

Dzina la API	Zikuonetsa	Wosintha	Tsiku Lotsiriza la Maluso (US)
LOXO-101 1223403-58-4	Mankhwala a oncology	Loxo Oncology	Ogasiti 21,2029

Tumizani imelo kwa ife

Mankhwala Mwatsatanetsatane

Zogulitsa

MFUNDO ZOFUNIKA KWAMBIRI

Mbiri

IC50: otsika nanomolar osiyanasiyana poletsa mamembala onse a TRK

LOXO-101 ndi choletsa tropomyosin receptor kinases (TRK) choletsa.

Banja la TRK la ma neurotrophin receptors ndi ma neurotrophin ligands amawongolera kukula kwa minyewa, kusiyanitsa ndi kupulumuka.

In vitro: Pakafukufuku wam'mbuyomu, LOXO-101 idayesedwa kuti isagwiritsidwe ntchito ndi kinase enzyme poletsa gulu la omwe si a TRK kinases pamlingo wa 1,000 nM ndi ATP wozungulira Km. Zotsatira zinawonetsa kuti LOXO-101 inali yayikulu kuposa 50% yoletsa kwa non-TRK kinase imodzi yokha, yomwe inali TNK2 yokhala ndi IC50 ya 576 nM. Kuphatikiza apo, kunalibe zoletsa za HERG kapena kuyang'anitsitsa kwa QT [1].

Mu vivo: Kafukufuku wazinyama adapeza kuti LOXO-101 idatha kuletsa kukula kwa chotupa cha vivo. Mbewa zamaliseche za Athymic zoyikiridwa ndi maselo a KM12 amathandizidwa pakamwa ndi LOXO-101 tsiku lililonse kwamasabata awiri, ndipo kuwonetseredwa kwa chotupa kumayesedwa, kuwonetsa kuthekera kwa LOXO-101 kuletsa kukula kwa chotupa cha-vivo [1].

Kuyesedwa kwachipatala: Kafukufuku wopitilira muyeso wa kuchuluka kwa kuchuluka kwa odwala omwe ali ndi zotupa zolimba (ClinicalTrials.gov no. NCT02122913) idachitika mu 2014 kuwunika chitetezo ndi PK ya LOXO-101. Odwala amathiridwa kamodzi kapena kawiri tsiku lililonse kwa masiku 28 atadwala mosalekeza m'magulu owonjezeka. Zambiri zoyambirira za PK ndi chitetezo zikuwonetsa kuti magawo am'magazi aulere a LOXO-101 ali pazigawo zogwirizana ndi chilengedwe kuti zilepheretse oncogenes a TRK. Pakafukufukuyu, wodwala woyamba komanso yekhayo adawonetsa kusakanikirana kwa TRK ndikuwonongeka kwamatenda mwachangu komwe kumawoneka ndi chithandizo cha LOXO-101 [1].

Buku:
[1] Doebele RC neri Al. Kusakanikirana kwa Oncogenic NTRK mu Wodwala Wofewa-Tissue Sarcoma Woyankha ku Tropomyosin-Related Kinase Inhibitor LOXO-101. Khansa Discov. 2015 Oct; 5 (10): 1049-57.

Kufotokozera

Larotrectinib (LOXO-101) ndi mpikisano wokonda mpikisano wa ATP, inhibitor yosankha ya tropomyosin-related kinase (TRK) yolandila mabanja, yokhala ndi nanomolar low 50% yoletsa motsutsana ndi ma isoform onse atatu (TRKA, B, ndi C).

Kuyesa Kwachipatala

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