Potent and Specific Jak2 Inhibitors for the Treatment of Blood Cancers
Identification of a Diverse Portfolio of Jak2 Small Molecule Inhibitors
None
Patent Number: US8367078B2
Application Number: US2010663521A
Inventor: Sayeski, Peter P. | Keserü, György M.
Priority Date: 6 Jun 2007
Priority Number: US8367078B2
Application Date: 12 Jul 2010
Publication Date: 5 Feb 2013
IPC Current: A61K000900 | A01N005926 | A61K000920 | A61K000948 | A61K003342 | A61K004700 | C07C004920 | C07C025500 | C07F000922 | G01N003320
US Class: 424400 | 424439 | 424451 | 424463 | 424464 | 424489 | 424601 | 436081 | 558303 | 558385 | 562008 | 562011 | 568008 | 568303 | 568307 | 568382 | 568414 | 568415 | 568700 | 568702
Assignee Applicant: University of Florida Research Foundation Inc.inesville
Title: Kinase inhibitor compounds
Usefulness: Kinase inhibitor compounds
Summary: (I) is useful for treating JAK2 mediated disorder and for reducing Jak2-dependent cell growth in a subject, preferably human, where: the JAK2 mediated disorder is hematological disease or disorder (including polycythemia vera, essential thrombocythemia, angiogenic myeloid metaplasia, and primary myelofibrosis), cancer (including leukemias (which is chronic myelogenous leukemia, acute myeloid leukemia and acute promyelocytic leukemia), lymphomas, myelomas and solid tumors), and a cardiac disease or disorder (including cardiac hypertrophy, cardiac ischemia-reperfusion and heart failure); the subject is identified as having the Jak2-V617F mutant, or K603Q, D620E or C644S mutation in the Jak2 JH2 domain; or the subject is identified as having the K603Q, D620E and C644S mutations in the Jak2 JH2 domain and is identified as not having the Jak2-V617F mutant (all claimed); and the cancer is e.g. chronic leukemia, polycythemia vera, Hodgkin's disease, fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, synovioma, mesothelioma, Ewing's tumor, leiomyosarcoma, rhabdomyosarcoma, colon carcinoma, pancreatic cancer, breast cancer, ovarian cancer, prostate cancer, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinomas, cystadenocarcinoma, medullary carcinoma, bronchogenic carcinoma, renal cell carcinoma, hepatoma, nile duct carcinoma, choriocarcinoma, seminoma, embryonal carcinoma, Wilm's tumor, cervical cancer, uterine cancer, testicular cancer, lung carcinoma, small cell lung carcinoma, bladder carcinoma, epithelial carcinoma, glioma, astrocytoma, medulloblastoma, craniopharyngioma, ependymoma, pinealoma, hemangioblastoma, acoustic neuroma, oligodenroglioma, schwannoma, meningioma, melanoma, neuroblastoma, and retinoblastoma. The ability of 2-(diethylaminomethyl)-4-[4-[3-(diethylaminomethyl)-4-hydroxy-phenyl]hex-3-en-3-yl]phenol (G6) to treat Jak2-V617F-induced hematopoetic disease was tested in severe combined immunodeficient (SCID) mouse model. The result showed that (G6) reduced human erythroleukemic cell induced increase in the percent of circulating blast cells by 50 percent.
Novelty: Treating janus kinases-2 mediated disorder e.g. cancer, comprises administering e.g. (diethylaminomethyl)-4-(4-((diethylaminomethyl)-hydroxy-phenyl)hexenyl)phenol, dibutoxyphosphoryloxypentanenitrile or ytterbium trihydroxide
診斷/治療
癌症/腫瘤
Jul 12, 2010
8,367,078
美國
