I-LOXO-101 1223403-58-4
Ingemuva
I-IC50: ibanga le-nanomolar eliphansi lokuvimbela wonke amalungu omndeni we-TRK
I-LOXO-101 iyi-tropomyosin receptor kinases (TRK) inhibitor.
Umndeni we-TRK wama-receptors we-neurotrophin kanye ne-neurotrophin ligands yawo ilawula ukukhula kwe-neuron, ukwahlukanisa nokusinda.
In vitro: Ocwaningweni olwedlule, i-LOXO-101 ihlolwe nge-off-target kinase enzyme yokuvimbela iphaneli lama-kinase angewona ama-TRK ekugxileni kwe-1,000 nM kanye ne-ATP lokugxila kwe-Km. Imiphumela ikhombise ukuthi i-LOXO-101 yayinokuvinjelwa okungaphezulu kokungu-50% nge-non-TRK kinase eyodwa kuphela, eyayiyi-TNK2 ene-IC50 ka-576 nM. Ngaphezu kwalokho, bekungekho ukuvinjelwa kwe-hERG efanelekile noma ukubonwa kwe-QT okude [1].
Ku-vivo: Ucwaningo lwezilwane luthole ukuthi i-LOXO-101 ikwazile ukuvimbela ukukhula kwe-vivo isimila. Amagundane anqunu e-Athymic ajojowe ngamaseli we-KM12 ayelashwa ngomlomo nge-LOXO-101 nsuku zonke amasonto ama-2, futhi kwabonwa ukuvinjelwa kwesimila esincike kumthamo, okukhombisa amandla we-LOXO-101 ukuvimbela ukukhula kwe-in-vivo tumor [1].
Isivivinyo somtholampilo: Isifundo se-multicenter phase I-escalation Study ezigulini ezinamathumba aqinile (ClinicalTrials.gov no. NCT02122913) yenziwa e-2014 ukuhlola ukuphepha ne-PK ye-LOXO-101. Iziguli zikhishwa kanye noma kabili nsuku zonke izinsuku ezingama-28 zokulandelwa okuqhubekayo kumaqoqo akhulayo. Idatha yokuqala ye-PK nokuphepha ikhombisa ukuthi amazinga we-plasma wamahhala we-LOXO-101 asezingxenyeni ezifanele zezinto eziphilayo ukuvimbela ama-oncogene e-TRK. Kulolu cwaningo, isiguli sokuqala futhi okuwukuphela kwaso esikhombise ukuhlanganiswa kwe-TRK kanye nokuhlehla okusheshayo kwesimila somtholampilo okubonwe ngokwelashwa kwe-LOXO-101 [1].
Inkomba:
[1] IDoebele RC et al. I-Oncogenic NTRK Fusion esigulini esineSoft-Tissue Sarcoma enempendulo kwiTropomyosin-Related Kinase Inhibitor LOXO-101. I-Cancer Discov. 2015 Okthoba; 5 (10): 1049-57.
Incazelo
I-Larotrectinib (i-LOXO-101) i-ATP-yokuncintisana ngomlomo, i-inhibitor ekhethiwe ye-tropomyosin-related kinase (TRK) yomndeni yokwamukela, ene-nanomolar low 50% yokugxila kokulwa nawo womathathu ama-isoforms (TRKA, B, no-C).
Isivivinyo Somtholampilo
| Inombolo ye-NCT | Umxhasi | Isimo | Usuku okuqalwa ngalo |
Isigaba |
| I-NCT03025360 | Bayer | Izimila Ezigcina Ukuhlanganiswa kwe-NTRK |
|
|
| I-NCT02637687 | Bayer | Izicubu Eziqinile Zifukamela I-NTRK Fusion | Disemba 16, 2015 |
Isigaba 1 | Isigaba 2 |
| I-NCT02122913 | Bayer | Izicubu Eziqinile Zifukamela I-NTRK Fusion | Meyi 4, 2014 |
Isigaba 1 |
| I-NCT03213704 | Isikhungo Somdlavuza Kazwelonke (i-NCI) | I-Advanced Malignant Solid Neoplasm | I-Ependymoma Ephindaphindayo | I-Ewing Sarcoma + Yesipelingi YasePeripheral Primitive Neuroectodermal Tumor | I-Glioma Ephindaphindayo | I-Hepatoblastoma Ephindaphindayo | I-Langerhans Cell Histiocytosis Ephindaphindayo | I-Recurrent Malignant Germ Cell Tumor | I-Recurrent Malignant Recurrent Recurrent | I-Non-Hodgkin Lymphoma | I-Osteosarcoma Ephindaphindayo | Isicubu SaseRhabdoid Esiphindaphindayo | I-Rhabdomyosarcoma Ephindaphindayo | I-Sarcoma Yesicubu Esiphindaphindayo | I-Refendory Ependymoma | I-Refractory Ewing Sarcoma + I-Peripheral Primitive Neuroectodermal Tumor | I-Refractory Glioma I-Refractory I-Refractory ye-Refractory I-Refractory I-Refractory ye-Refractory I-Malignant Glioma | I-Neoplasm Solid Solid Refractory | I-Refractory Neuroblastoma | I-Refractory Non-Hodgkin Lymphoma | I-Osteosarcoma Ekhanyelayo | I-Refractory Primary Central Nervous System Neoplasm | I-Refractory Rhabdoid Tumor | I-Refractory Rhabdomyosarcoma | I-Wilms Tumor | Julayi 24, 2017 |
Isigaba 2 |
| I-NCT02465060 | Isikhungo Somdlavuza Kazwelonke (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 | Izinso I-Carcinoma | Isibindi Ne-Intrahepatic Bile Duct Carcinoma | Isibindi Ne-Intrahepatic Bile Duct Carcinoma | | I-Neoplasm yesibeletho esibi | I-Glioma Ephindaphindayo | I-Head and Neck Carcinoma Ephindaphindayo | I-Carcinoma Yesibindi Esiphindaphindayo | I-Lung Carcinoma Ephindaphindayo | I-Lymphoma Ephindaphindayo | I-Neoplasm Eqinile Yesibindi Esiphindayo | I-Melanoma Ephindayo Isikhumba Esikhunjulwayo Esiphindaphindayo | Indlala Yegilo Ephindiwe I-Carcinoma | Umdlavuza Ophindaphindayo Wesibeletho Womzimba | I-Refractory Lymphoma | I-Reflectory Malignant Solid Neoplasm | I-Refractory Plasma Cell Myeloma | Isikhumba I-Carcinoma | I-Thyroid Gland Carcinoma | I-Uterine Corpus Cancer | Agasti 12, 2015 |
Isigaba 2 |
| I-NCT03834961 | Iqembu Lezingane le-Oncology | I-National Cancer Institute (NCI) | I-Central Neervasm System Neoplasm | I-Infantile Fibrosarcoma | I-Leukemia Ephindaphindekayo Ye-Leukemia | I-Refuseory Leukemia Ebukhali | I-Neoplasm Eqinile | Septhemba 18, 2019 |
Isigaba 2 |
| I-NCT04142437 | Bayer | Isimila Esishubile Sendawo Esiphezulu noma EsineMetastatic Ukugcina i-NTRK Gene Fusion | Ephreli 3, 2020 |
|
| I-NCT03155620 | Isikhungo Somdlavuza Kazwelonke (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 | Langerhans Cell Histiocytosis | I-Malignant Glioma | I-Recurrent Childhood Rhabdomyosarcoma | I-Recurrentoma yaseRoma I-Hepatoblastoma Ephindaphindayo | I-Langerhans Cell Histiocytosis Ephindaphindayo | Isigaxa Esibuhlungu Esiphindaphindayo Se-Germ Cell | I-Neoplasm Eqinile Yesibindi Esiphindaphindayo | I-Medulloblastoma Ephindaphindayo | I-Neuroblastoma Ephindaphindayo | I-Recurrent Non-Hodgkin Lymphoma | I-Recurrent Recuror Recurrent Recurrent Recurrent Recurrent Recurrent | Phindaphinda Soft Tissue Sarcoma | Refractory Ewing Sarcoma | Refractory Glioma | Refractory Hepatoblastoma | Refractory Langerhans Cell Histiocytosis | Refractory ebulalayo Amagciwane Engeke Esaba Cell isimila | Refractory ebulalayo Solid Neoplasm | Refractory Medulloblastoma | Refractory unesimila ebuchosheni | Refractory Non-Hodgkin Lymphoma | Refractory Osteosarcoma | Refra ctory Peripheral Primitive Neuroectodermal Tumor | Refractory Primary Central Nervous System Neoplasm | Refractory Rhabdoid Tumor | Refractory Rhabdomyosarcoma | Rhabdoid Tumor | Stage III Osteosarcoma AJCC v7 | Isigaba III Isishubhu Esithambile Sarcoma AJCC v7 | Isiteji IV Astoma St I-OCCS | Isigaba IVA Osteosarcoma AJCC v7 | Isigaba IVB Osteosarcoma AJCC v7 | I-Wilms Tumor | Julayi 24, 2017 |
Isigaba 2 |
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