I-China LOXO-101 1223403-58-4 abavelisi kunye nabathengisi

I-LOXO-101 1223403-58-4

Inkcazo emfutshane:

Igama le-API	Uphawu	Umvelisi	Umhla wokuphelelwa kwepatent (iUS)
I-LOXO-101 1223403-58-4	Iziyobisi ze-Oncology	ILoxo Oncology	Oktobha 21, 2029

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I-IC50: uluhlu oluphantsi lwe-nanomolar yokuthintela onke amalungu osapho lwe-TRK

I-LOXO-101 yi-tropomyosin receptor kinases (TRK) inhibitor.

Usapho lwe-TRK lwee-receptors ze-neurotrophin kunye ne-neurotrophin ligands yazo ilawula ukukhula kwe-neuron, umahluko kunye nokusinda.

In vitro: Kwisifundo sangaphambili, i-LOXO-101 yavavanywa kwi-enaseme ye-kinase ye-inaseme ekugxilwe kuyo ngokuchasene nephaneli ye-non-TRK kinases kuxinzelelo lwe-1,000 nM kunye ne-ATP yokugxila kwi-Km. Iziphumo zabonisa ukuba i-LOXO-101 yayinkulu kune-50% yokuthintela inye kuphela engeyiyo-TRK kinase, eyayiyi-TNK2 ene-IC50 ye-576 nM. Ngaphaya koko, bekungekho kuthintelwa kwe-hERG efanelekileyo okanye ukubonwa kwe-QT ixesha elide [1].

Kwi-vivo: Uphando lwezilwanyana lufumanise ukuba i-LOXO-101 ikwazile ukuthintela ukukhula kwe-vivo tumor. Iimpuku ze-Athymic ze-injude ezijojowe ngeeseli ze-KM12 zazinyangwa ngomlomo nge-LOXO-101 yonke imihla kwiiveki ze-2, kwaye kwaqwalaselwa ithosi yokuxhomekeka kwidosi, ebonisa amandla e-LOXO-101 ukuthintela ukukhula kwe-in-vivo tumor [1].

Uvavanyo lwezonyango: Isigaba sokufunda esinyukayo sokunyusa idosi kwizigulana ezinamathumba aqinileyo (ClinicalTrials.gov no. NCT02122913) yenziwa kwi-2014 ukuvavanya ukhuseleko kunye ne-PK ye-LOXO-101. Izigulana zitshiswa kanye okanye kabini imihla ngemihla kwiintsuku ezingama-28 zokuqhubeka kwedosi kwii-cohorts ezikhulayo. Idatha yokuqala ye-PK kunye neenkcukacha zokhuseleko zibonisa ukuba amanqanaba e-plasma asimahla e-LOXO-101 akwimixholo efanelekileyo yezinto eziphilayo ukuthintela ii-oncogenes ze-TRK. Kolu phando, isigulana sokuqala kunye nesinye kuphela sibonise i-TRK fusion kunye nokukhawuleza kokuphazamiseka kwethumba okubonakalayo kunyango lwe-LOXO-101 [1].

Isalathiso:
[1] I-Doebele RC et al. I-Oncogenic NTRK Fusion kwisigulana esineSoft-Tissue Sarcoma eneMpendulo kwiTropomyosin-ehambelana neKinase Inhibitor LOXO-101. Umhlaza Discov. 2015 Okt; 5 (10): 1049-57.

Inkcazo

I-Larotrectinib (i-LOXO-101) ngumlomo okhuphisanayo we-ATP, i-inhibitor ekhethiweyo ye-tropomyosin enxulumene ne-kinase (TRK) ye-receptors yosapho, ene-nanomolar ephantsi ye-50% yokugxininisa kwi-isoforms (TRKA, B, kunye no-C).

Uvavanyo lweKlinikhi

Inombolo ye-NCT	Umxhasi	Imeko	Umhla wokuqala	Isigaba
I-NCT03025360	Bayer	Amathumba Ukugcina i-NTRK Fusion
I-NCT02637687	Bayer	Amathumba aQhelekileyo aGcina i-NTRK Fusion	UDisemba 16, 2015	Isigaba 1 \| Isigaba 2
I-NCT02122913	Bayer	Amathumba aQhelekileyo aGcina i-NTRK Fusion	Nge-4 kaMeyi 2014	Isigaba 1
I-NCT03213704	IZiko leSizwe loMhlaza (i-NCI)	I-Advanced Malignant Solid Neoplasm \| I-Ependymoma ephindaphindayo \| I-Ewing Sarcoma + yePeripheral Primitive Neuroectodermal Tumor \| I-Glioma ephindaphindayo \| I-Hepatoblastoma ephindaphindayo \| I-Langerhans Cell Histiocytosis \| Isifo esiPhindaphindiweyo seLungu leSeli \| Isifo esibuhlungu esibuhlungu esiphindaphindiweyo \| Isifo esibuhlungu esibuhlungu esiphindaphindiweyo \| I-non-Hodgkin Lymphoma \| I-Osteosarcoma ephindaphindayo \| Rhabdoid Tumor ephindaphindayo \| Rhabdomyosarcoma ephindaphindayo \| I-Sarcoma yeTissue ephindaphindayo \| I-Refendory ye-Ependymoma \| I-Refractory Ewing Sarcoma + I-Peripheral Primitive Neuroectodermal Tumor \| I-Refractory Glioma ye-Refractory Isifo se-Refractory Isifo se-Refractory. I-Malignant Glioma \| I-Refractory Malignant Solid Neoplasm \| I-Refractory Neuroblastoma \| I-Refractory engeyiyo i-Hodgkin Lymphoma \| I-Osteosarcoma ye-Refractory \| I-Neoplasm ye-Nevmosis yeNtsholongwane \| I-Refractory Rhabdoid Tumor \| I-Refractory Rhabdomyosarcoma \| i-Wilms Tumor	Julayi 24, 2017	Isigaba 2
I-NCT02465060	IZiko leSizwe loMhlaza (i-NCI)	I-Advanced Malignant Solid Neoplasm \| Bladder Carcinoma \| Breast Carcinoma \| Cervical Carcinoma \| Colon Carcinoma \| Colorectal Carcinoma \| Endometrial Carcinoma \| Esophageal Carcinoma \| Gastric Carcinoma \| Glioma \| Head and Neck Carcinoma \| Izintso I-Carcinoma \| Isibindi ne-Intrahepatic Bile Duct Carcinoma \| Isibindi kunye ne-Intrahepatic Bile Duct Carcinoma \| \| Isisu esibuhlungu se-Uterine Neoplasm \| I-Melanoma \| I-Ovarian Carcinoma \| I-Pancreatic Carcinoma \| I-Plasma Cell Myeloma \| I-Prostate Carcinoma \| I-Rectal Carcinoma \| I-Bladder Carcinoma eQhelekileyo \| I-Breast Carcinoma ephindaphindayo \| I-Carcinoma ephindayo yomlomo wesibeleko \| I-Colon Carcinoma ephindaphindayo \| I-Carcinoma eqhubekayo yaso rhoqo \| \| I-Glioma ephindaphindayo \| INtloko eQhubekayo kunye neNtamo yeCarcinoma \| Isibindi seCarcinoma esiqhelekileyo \| I-Lung Carcinoma ephindaphindayo \| I-Lymphoma ephindaphindayo \| I-Neoplasm eQinisekayo eQhelekileyo \| I-Melanoma ephindayo Ulusu oluphindaphindeneyo lweCarcinoma \| Ukuphindaphinda kweTyroid Gland ICarcinoma \| Umhlaza wesibeleko seCortus \| I-Refractory Lymphoma \| I-Refractory Malignant Solid Neoplasm \| I-Refractory Plasma Cell Myeloma \| Ulusu lweCarcinoma \| I-Thyroid Gland Carcinoma \| I-Uterine Corpus Cancer	Nge-12 ka-Agasti ka-2015	Isigaba 2
I-NCT03834961	Iqela le-Oncology yaBantwana \| IZiko leSizwe loMhlaza (i-NCI)	INervous System yeNeoplasm \| I-Infantile Fibrosarcoma \| Ileukemia ePhinda phindeneyo \| Ileptemia ebukekayo \| I-Neoplasm eqinileyo	NgoSeptemba 18, 2019	Isigaba 2
I-NCT04142437	Bayer	Ekuhlaleni okuPhucukileyo okanye kweMetastatic Solor Tumor Ukugcina i-NTRK Gene Fusion	Nge-3 ka-Epreli 2020
I-NCT03155620	IZiko leSizwe loMhlaza (i-NCI)	I-Advanced Malignant Solid Neoplasm \| Ann Arbor Stage III Non-Hodgkin Lymphoma \| Ann Arbor Stage IV Non-Hodgkin Lymphoma \| Histiocytic Sarcoma \| Juvenile Xanthogranuloma \| I-Langerhans Cell Histiocytosis \| I-Malignant Glioma \| Ukuphindaphinda kweRhabdomyosarcoma \| I-Recurrent Recoma \| I-Recurrentoma yaseRoma Ukuphindaphinda kweHepatoblastoma \| I-Langerhans Cell Histiocytosis eQhubekayo \| Isilonda esibuhlungu esibuhlungu seGerm Cell \| I-Neoplasm eQinisekayo eQhubekayo \| I-Medulloblastoma ephindaphindayo \| I-Neuroblastoma eqhubekayo \| I-Recurrent non-Hodgkin Lymphoma \| I-Osteosarcoma yaphindaphindeka \| I-Recurative Recurrent Recurrent \| Ukuphindaphinda iTissue Sarcoma \| I-Refractory Ewing Sarcoma \| I-Refractory Glioma \| I-Refractory Hepatoblastoma \| I-Refractory Langerhans Cell Histiocytosis \| I-Refractory Malignant Germ Cell Tumor \| I-Refractory Malignant Solid Neoplasm \| I-Refractory Medulloblastoma \| I-Refractory Neuroblastoma \| Refractory Neuroblastoma \| I-ctory Peripheral Primitive Neuroectodermal Tumor \| Inkqubo ye-Refractory Primary Central Nervous System Neoplasm \| Refractory Rhabdoid Tumor \| Refractory Rhabdomyosarcoma \| Rhabdoid Tumor \| Stage III Osteosarcoma AJCC v7 \| Isigaba III Isisisi Esithambileyo I-Sarcoma AJCC v7 \| Isigaba IV Isithsaba \| Inqanaba le-IVA Osteosarcoma AJCC v7 \| Inqanaba IVB Osteosarcoma AJCC v7 \| I-Wilms Tumor	Julayi 24, 2017	Isigaba 2