China LOXO-101 1223403-58-4 vagadziri uye vanotengesa

LOXO-101 1223403-58-4

Tsananguro Pfupi:

Zita re API	Chiratidzo	Mugadziri	Patent Kupera Zuva (Iyo US)
LOXO-101 1223403-58-4	Oncology mushonga	Loxo Oncology	Gumiguru 21,2029

Tumira neindaneti kwatiri

Chigadzirwa Chigadzirwa

Chigadzirwa Mateki

CHIDZIDZO CHIDZIDZO

Mhemberero

IC50: yakaderera nanomolar renji yekudzivirira yeese mitezo yemhuri yeTrK

LOXO-101 inonzi tropomyosin receptor kinases (TRK) inhibitor.

Mhuri yeTRK yemaurotrophin receptors uye yavo neurotrophin ligands inodzora kukura kweiyo neuron, kusiyanisa uye kurarama.

In vitro: Muchidzidzo chekare, LOXO-101 yakaongororwa ye-off-target kinase enzyme inhibition inopesana nedanho reasina-TRK kinases pakumisikidzwa kwe1,000 nM uye ATP kutenderera kwakatenderedza Km. Mhedzisiro yakaratidza kuti LOXO-101 yaive nepamusoro pe50% inhibition yeimwe chete isiri-TRK kinase, yaive TNK2 ine IC50 ye576 nM. Zvakare, pakange pasina akakodzera hERG inhibition kana yakareba QT yekutarisa [1].

Mu vivo: Chidzidzo chemhuka chakawana kuti LOXO-101 yakakwanisa kudzivisa mu vivo bundu kukura. Athymic mbeva dzisina kupfeka dzakabayiwa nemaKM12 maseru aibatwa nemuromo neLoXO-101 zuva rega rega kwemavhiki maviri, uye dhosi-inoenderana nethumba inhibition yakaonekwa, zvichiratidza kugona kweLOXO-101 kudzivirira in-vivo bundu kukura [1].

Clinical kutongwa: Chikamu chakasiyana-siyana I dose-kukwira kudzidza mune varwere vane advanced tumors yakasimba (ClinicalTrials.gov no. NCT02122913) yakaitwa mu2014 kuongorora kuchengetedzeka uye PK yeLOXO-101. Varwere vanoiswa kamwe chete kana kaviri zuva nezuva kwemazuva makumi maviri nemasere ekuenderera mberi kwedhosi mumakirabhu anowedzera. Yekutanga PK uye data rekuchengetedza zvinoratidza kuti mahara emahara eplasma eLOXO-101 ari pazvinhu zvinoenderana nehupenyu kutadzisa TRK oncogenes. Muchidzidzo ichi, wekutanga uye wega murwere akaratidza TRK fusion uye nekukurumidza kliniki bundu regression rakaonekwa nekurapwa kweLOXO-101 [1].

Referensi:
[1] Doebele RC et al. Iyo Oncogenic NTRK Fusion muMurwere ane Soft-Tissue Sarcoma ine Mhinduro kune iyo Tropomyosin-Inoenderana Kinase Inhibitor LOXO-101. Kenza Discov. 2015 Oct; 5 (10): 1049-57.

Tsananguro

Larotrectinib (LOXO-101) ndeye ATP-inokwikwidza muromo, inosarudza inhibitor yeiyo tropomyosin-yakabatana kinase (TRK) mitezo yemhuri, ine yakaderera nanomolar 50% inhibitory concentrations against all three isoforms (TRKA, B, and C).

Kliniki Kuedzwa

NCT Nhamba	Sponsor	Mamiriro	Kutanga Zuva	Chikamu
NCT03025360	Bayer	Tumors Kuchengeta NTRK Fusion
NCT02637687	Bayer	Solor Tumors Kuchengeta NTRK Fusion	Zvita 16, 2015	Phase 1 \| Chikamu 2
NCT02122913	Bayer	Solor Tumors Kuchengeta NTRK Fusion	Chivabvu 4, 2014	Chikamu 1
NCT03213704	National Cancer Institute (NCI)	Yepamberi Yakakomba Yakashata Neoplasm \| Yazvino Ependymoma \| Yazvino Ewing Sarcoma + Peripheral Primitive Neuroectodermal Tumor \| Dzokororo Glioma \| Dzokororo Hepatoblastoma \| Dzokororo Langerhans Cell Histiocytosis \| Dzokororo Yakakomba YeGerm Cell Tumor \| Kudzokororazve Malignant Guroma Kupora \| Kudzokorora \| Kwete-Hodgkin Lymphoma \| Osteosarcoma Yakadzokororwa \| Rhabdoid Tumor Inodzokororwa \| Rhabdomyosarcoma Inodzokororwa \| Dzokororo Tissue Sarcoma \| Refractory Ependymoma \| Refractory Ewing Sarcoma + Peripheral Primitive Neuroectodermal Tumor \| Refractory Glioma \| Refractory Chironda cheRepistorioma Reopistorioma Malignant Glioma \| Refractory Malignant Solid Neoplasm \| Refractory Neuroblastoma \| Refractory Isiri-Hodgkin Lymphoma \| Refractory Osteosarcoma \| Refractory Primary Central Nervous System Neoplasm \| Refractory Rhabdoid Tumor \| Refractory Rhabdomyosarcoma \| Wilms Tumor.	Chikunguru 24, 2017	Chikamu 2
NCT02465060	National Cancer Institute (NCI)	Yepamberi Malignant Solid Neoplasm \| Bladder Carcinoma \| Breast Carcinoma \| Cervical Carcinoma \| Colon Carcinoma \| Colorectal Carcinoma \| Endometrial Carcinoma \| Esophageal Carcinoma \| Gastric Carcinoma \| Glioma \| Musoro uye Neck Carcinoma \| Itsvo Carcinoma \| Chiropa uye Intrahepatic Bile Duct Carcinoma \| Chiropa uye Intrahepatic Bile Duct Carcinoma \| \| Malignant Uterine Neoplasm \| Melanoma \| Ovarian Carcinoma \| Pancreatic Carcinoma \| Plasma Cell Myeloma \| Prostate Carcinoma \| Rectal Carcinoma \| Dzokororo Bladder Carcinoma \| Dzokororo Breast Carcinoma \| Dzokororo Cervical Carcinoma \| Dzokororo Colon Carcinoma \| Dzokorororomarara Gomarara Gomarara \| \| Dzokororo Glioma \| Musoro Unodzokororwa uye Neck Carcinoma \| Dzokororo Chiropa Carcinoma \| Dzokororo Lung Carcinoma \| Dzokororo Lymphoma \| Dzokororo Yakakomba Solid Neoplasm \| Dzokororo Melanoma \| Dzokororo Ovarian Carcinoma \| Dzokororo Pancreatic Carcinoma \| Dzokororo Plasma Cell Myeloma \| Inodzokorodza \| Dzokororo Ganda Carcinoma \| Dzokororo Glandi Gland Carcinoma \| Yazvino Uterine Corpus Cancer \| Refractory Lymphoma \| Refractory Inokanganisa Solid Neoplasm \| Refractory Plasma Cell Myeloma \| Ganda Carcinoma \| Thyroid Gland Carcinoma \| Uterine Corpus Cancer	Nyamavhuvhu 12, 2015	Chikamu 2
NCT03834961	Yevana Oncology Boka \| National Cancer Institute (NCI)	Central Nervous System Neoplasm \| Infantile Fibrosarcoma \| Inowanzoitika Leukemia \| Refractory Acute Leukemia \| Solid Neoplasm	Nyamavhuvhu 18, 2019	Chikamu 2
NCT04142437	Bayer	Munzvimbo Yepamberi kana Metastatic Solid Tumor Kuchengeta iyo NTRK Gene Fusion	Kubvumbi 3, 2020
NCT03155620	National Cancer Institute (NCI)	Yepamberi Yakashata Yakasimba Neoplasm \| Ann Arbor Stage III Isiri-Hodgkin Lymphoma \| Ann Arbor Stage IV Isiri-Hodgkin Lymphoma \| Histiocytic Sarcoma \| Juvenile Xanthogranuloma \| Langerhans Cell Histiocytosis \| Malignant Glioma \| Dzokororo Yevacheche Rhabdomyosarcoma \| Sarurudzo Dzokororo Hepatoblastoma \| Dzokororo Langerhans Cell Histiocytosis \| Dzokororo Yakakomba Germ Cell Tumor \| Dzokororo Yakakomba Neoplasm Yakasimba \| Dzokororo Medulloblastoma \| Dzokororo Neuroblastoma \| Dzokororo Isiri-Hodgkin Lymphoma \| Dzokororo Osteosarcoma \| Dzokorodzano Yakapetwa \| \| Dzokororo Tissue Sarcoma \| Refractory Ewing Sarcoma \| Refractory Glioma \| Refractory Hepatoblastoma \| Refractory Langerhans Cell Histiocytosis \| Refractory Inonyangadza YeGerm Cell Tumor \| Refractory Inokanganisa Solid Neoplasm \| Refractory Medulloblastoma \| Refractory Neuroblastoma \| Refractory Neuroblastoma \| Refractory Neuroblastoma \| Refractory Neuroblastoma \| ctory Peripheral Primitive Neuroectodermal Tumor \| Refractory Primary Central Nervous System Neoplasm \| Refractory Rhabdoid Tumor \| Refractory Rhabdomyosarcoma \| Rhabdoid Tumor \| Stage III Osteosarcoma AJCC v7 \| Stage III Nyoro Nyoro Sarcoma AJCC v7 \| Stage IV Ostearc St \| Chikamu IVA Osteosarcoma AJCC v7 \| Chikamu IVB Osteosarcoma AJCC v7 \| Wilms Tumor	Chikunguru 24, 2017	Chikamu 2