Shiinaha LOXO-101 1223403-58-4 saarayaasha iyo alaabada

LOXO-101 1223403-58-4

Sharax Gaaban:

Magaca API	Tilmaam	Hal abuure	Taariikhda Waqtiga Patent uu dhacayo (Mareykanka)
LOXO-101 1223403-58-4	Daawada Oncology	Loxo Oncology	Oktoobar 21,2029

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IC50: kala duwanaanta nanomolar ee ka hortagga dhammaan xubnaha qoyska ee TRK

LOXO-101 waa xakamaysade xakameeye qaata (TRK).

Qoyska TRK ee soo dhaweeyayaasha neurotrophin iyo jilciyayaashooda neurotrophin ayaa nidaamiya koritaanka neerfaha, kala duwanaanta iyo badbaadada.

In vitro: Daraasadii hore, LOXO-101 waxaa lagu qiimeeyay ka hortagga bartilmaameedka kinase enzyme ee kahortaga guddi aan kinsi ahayn TRK iyadoo la fiirinayo 1,000 nM iyo uruurinta ATP ee agagaarka Km. Natiijooyinka waxay muujiyeen in LOXO-101 uu ka weynaaday 50% ka hortag kaliya hal aan ahayn TRK kinase, taasoo ahayd TNK2 oo leh IC50 ee 576 nM. Intaa waxaa sii dheer, ma jirin wax xakameyn ah oo loo yaqaan 'hERG inhibition' ama indho indheyn QT dheeri ah [1].

In vivo: Daraasada xayawaanku waxay ogaatay in LOXO-101 ay awood u leedahay inay joojiso koritaanka burooyinka vivo. Jiirarka qaawan ee jimicsiga lagu duray ee unugyada KM12 waxaa afka laga mariyey LOXO-101 maalin kasta 2 usbuuc, waxaana la arkay ka hortagga burooyinka ku tiirsan qiyaasta, taasoo muujineysa awooda LOXO-101 ee ka hortagga koritaanka burada-in-vivo [1].

Tijaabinta bukaan socodka: Daraasad heer sare ah oo kordhinta wajiga badan ee bukaanada leh burooyinka adag ee adag (ClinicalTrials.gov no. NCT02122913) ayaa lagu qabtay 2014 si loo qiimeeyo amniga iyo PK ee LOXO-101. Bukaanka waxaa la cabirayaa hal ama labo jeer maalin kasta 28 maalmood oo ah qadar qaadasho joogto ah oo ku sii kordheysa wadahalada. Hordhaca PK iyo xogta badbaadada waxay muujinayaan in heerarka plazma-ka ee bilaashka ah ee LOXO-101 ay yihiin uruurinta bayooloji ahaan ee khuseeya joojinta TRK oncogenes. Daraasaddan, bukaanka ugu horreeya iyo kan keliya ayaa muujiyay isugeynta 'TRK fusion' iyo dib-u-dhiska burooyinka bukaan-socodka ee degdegga ah ee lagu arkay daaweynta LOXO-101 [1].

Tixraac:
[1] Doebele RC et al. Fududeeyaha 'Oncogenic NTRK Fusion' ee bukaan-socodka leh Sarcoma-Cadka jilicsan oo leh Jawaab-celinta Tropomyosin-Related Kinase Inhibitor LOXO-101. Kansarka Kansarka. 2015 Oktoobar; 5 (10): 1049-57.

Sharaxaad

Larotrectinib (LOXO-101) waa hadal afka ah oo loo yaqaan 'ATP-tartame', xulista ka-hortagga qaboojiyeyaasha qoyska ee loo yaqaan 'troomyosin-kinase (TRK)', oo leh nanomolar 50% xoogsaarid xaddidan oo ka dhan ah dhammaan saddexda isbarbar dhigga (TRKA, B, iyo C).

Tijaabada Caafimaadka

Lambarka NCT	Kafaalasho	Xaaladda	Taariikhda billowga	Wejiga
NCT03025360	Baay	Burooyinka ku xareysan NTRK Fusion
NCT02637687	Baay	Burooyinka Adag ee Lagu Xannaaneeyo NTRK Fusion	Diisambar 16, 2015	Wajiga 1 \| Wajiga 2
NCT02122913	Baay	Burooyinka Adag ee Lagu Xannaaneeyo NTRK Fusion	4-ta May, 2014	Wajiga 1
NCT03213704	Machadka Kansarka Qaranka (NCI)	Cudurka Neoplasm Xanuun daran \| Soo noqnoqda Ependymoma \| Ewing Sarcoma soo noqnoqda + Peripheral Primitive Neuroectodermal Tumor \| Glioma soo noqnoqday \| Hepatoblastoma soo noqnoqda \| Soo noqnoqda Langerhans Cell Histiocytosis \| Dhibaatada soo noqnoqota ee Jeermiska Jeermiska Dareemka \| Lymphoma-aan Hodgkin \| Cudurka Osteosarcoma ee soo noqnoqda \| Soo noqnoqda Rumo Tumoor \| Rhabdomyosarcoma oo soo noqnoqota \| Cadka jilicsan ee soo noqnoqda Sarcoma \| Qalbi jabinta Ependymoma \| Buro Eigh Sarcoma + Gawaarida Gawaarida Gawaarida \| Cudurka Cudurka Qaaxada \| Cudurka Qalitaanka \| Cillad-xumo Glioma \| Neefsasho Xanuun daran oo Neoplasm \| Refractory Neuroblastoma \| Refractory Non-Hodgkin Lymphoma \| Osteosarcoma Refractory \| Nidaamka neerfaha ee aasaasiga ah ee neoplasm \| Bugta Rhabdoid Tumor \| Rhabdomyosarcoma oo diidan \| Wilms Tumor	24-Luulyo, 2017	Wajiga 2
NCT02465060	Machadka Kansarka Qaranka (NCI)	Neoplasm Xanuun Xanuun Leh \| Kaadiheysta Kaadiheysta \| Carcinoma Naaska \| Carcinoma ilmo galeenka \| Colon Carcinoma \| Carcinoma Colorectal \| Endometrial Carcinoma \| Esophageal Carcinoma \| Kansarka caloosha \| Glioma \| Madaxa iyo Neck Carcinoma \| Kilinji Kelyaha \| Beerka iyo Intrahepatic Bile Ductin \| Xanuunka Uterine Neoplasm \| Melanoma \| Carcinoma Ovarian \| Carcano Pancreatic \| Plasma Cell Myeloma \| Prostate Carcinoma \| Kaadi goynta kaadiheysta \| Carcinoma soo noqnoqota \| Carcinoma soo noqnoqota \| Carcinoma soo noqnoqota \| Carcinoma soo noqnoqota \| \| Glioma soo noqnoqota \| Madaxa soo noqnoqda iyo qoorta carcinoma \| carcinoma beerka soo noqnoqota \| carbinoma soo noqnoqota \| soo noqnoqda Lymphoma \| soo noqnoqda malignant Solid neoplasm \| soo noqnoqda melanoma \| soo noqnoqodka cudurka kansarka ovarian carcinoma Kansarka maqaarka ee soo noqnoqda \| Qanjirka 'Thyroid Gland' Carcinoma \| Cudurka Kansarka Ilmo-galeenka ee Soo noqnoqda \| Lymphoma Refractory \| Cudurka 'Neoplasm Solid' oo liidata \| Myeloma Cell Plasma oo diidan \| Carcinoma Maqaarka \| Kansarka qanjirka 'Thyroid Gland' \| Kansarka Uterine Corpus	Ogast 12, 2015	Wajiga 2
NCT03834961	Kooxda Kansarka Carruurta \| Machadka Kansarka Qaranka (NCI)	Nidaamka neerfaha ee neoplasm \| Fibrosarcoma dhallaanka ah \| Leukemia Xanuun Ba'an \| Neefsasho Xanuun Leukemia \| Xanuun Neoplasm	Sebtember 18, 2019	Wajiga 2
NCT04142437	Baay	Maxalliga Horukacsan ama Burooyinka adag ee Mastarka ah ee Lagu Xaraysto NTRK Gene Fusion	3 Abriil, 2020
NCT03155620	Machadka Kansarka Qaranka (NCI)	Neoplasm Xanuun Xanuun Leh \| Ann Arbor Stage III Non-Hodgkin Lymphoma \| Ann Arbor Stage IV Non-Hodgkin Lymphoma \| Sarcoma Histiocytic \| Juvenile Xanthogranuloma \| Langerhans Cell Histiocytosis \| Malignant Glioma \| Rhabdomyosarcoma Caruurnimada Soo noqnoqota \| Gelitaanka Ento \| Soo noqnoqda Hepatoblastoma \| Soo noqnoqodka Langerhans Cell Histiocytosis \| Soo noqnoqda Malmogta Germ Cell Tumor \| Soo noqnoqda Malignant Solid Neoplasm \| Soo noqnoqda Medulloblastoma \| Soo noqnoqda Neuroblastoma \| Soo noqnoqda Non-Hodgkin Lymphoma \| Soo noqnoqodka Osteosarcoma \| Nidaamka Nidaamka Nidaamka Cudurka Dabeecadeed ee caadiga ah \| \| Cadka jilicsan ee soo noqnoqda Sarcoma \| Ewing Sarcoma jilicsan \| Refractory Glioma \| Refractory Hepatoblastoma \| Refractory Langerhans Cell Histiocytosis \| Neefsashada Qalitaanka Jeermiska Jeermiska Jecel \| Qalitaanka Xanuunka Xanuunka Xun ee Qaldan \| Qalitaanka Neuroblastoma \| Refractory Neuroblastoma \| Refractory Neuroblastoma \| xuubka 'Peripheral Primitive Neuroectodermal Tumo' \| Nidaamka neerfaha ee aasaasiga ah ee neoplasm \| barar Rhabdoid barar \| Rhabdomyosarcoma diidan \| Tumor Rhabdoid \| Marxaladda III Osteosarcoma AJCC v7 \| Heerka III Cadka jilicsan Sarcoma AJCC v7 \| Stage III \| Marxaladda IVA Osteosarcoma AJCC v7 \| Marxaladda IVB Osteosarcoma AJCC v7 \| Wilms Tumor	24-Luulyo, 2017	Wajiga 2