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    COMPOUNDS FOR CANCERS DRIVEN BY BRAF MUTATION
    1.
    发明申请
    COMPOUNDS FOR CANCERS DRIVEN BY BRAF MUTATION 审中-公开

    公开(公告)号：WO2023070076A1

    公开(公告)日：2023-04-27

    申请号：PCT/US2022/078492

    申请日：2022-10-21

    申请人： THE BOARD OF TRUSTEES OF THE UNIVERSITY OF ILLINOIS ,  HERGENROTHER, Paul J. ,  KELLY, Aya Matsunaga

    发明人： KELLY, Aya Matsunaga ,  HERGENROTHER, Paul J.

    IPC分类号： C07D417/04 ,  C07D417/14 ,  A61K31/427 ,  A61P35/00

    摘要： The expression of the P-glycoprotein (P-gp) efflux transporter at the blood−brain interface impedes BBB penetrance of most small molecules. Designing efflux liabilities out of compounds can be laborious and there is no generalizable approach to transform periphery-limited agents to ones active in the CNS. A target-agnostic, prospective assessment of P-gp efflux using diverse compounds indicated a reduction in molecular size or appending a carboxylic acid that enabled evasion of P-gp efflux in cell-based experiments and in mice. Such strategy was applied to transform a periphery-limited V600EBRAF inhibitor, dabrafenib, into compounds that possess potent and selective anti-cancer activity, but now also evaded P-gp-mediated efflux. When compared to dabrafenib, the compound developed herein (everafenib) has superior BBB penetrance and superior efficacy in an intracranial mouse model of metastatic melanoma, suggesting it as a lead candidate for the treatment of melanoma metastases to the brain and gliomas with BRAF mutation.

    COMBINATION THERAPY FOR THE TREATMENT OF UVEAL MELANOMA
    2.
    发明申请
    COMBINATION THERAPY FOR THE TREATMENT OF UVEAL MELANOMA 审中-公开

    公开(公告)号：WO2020072774A1

    公开(公告)日：2020-04-09

    申请号：PCT/US2019/054500

    申请日：2019-10-03

    申请人： THE BOARD OF TRUSTEES OF THE UNIVERSITY OF ILLINOIS ,  HERGENROTHER, Paul J. ,  BOUDREAU, Matthew Wesley

    发明人： HERGENROTHER, Paul J. ,  BOUDREAU, Matthew Wesley

    IPC分类号： A61K31/416 ,  A61K31/495 ,  A61K31/519

    摘要： Synergistic drug combinations with the small molecule PAC-1 against uveal or cutaneous melanoma. There are no current targeted drug treatments for the mutations associated with uveal melanoma. Despite primary radiation or surgical therapy, up to 50% of patients eventually develop metastatic disease, for which there is no standard therapy nor treatment shown to improve overall survival. Drug combinations with PAC‑1 allow the use of lower dosages of this compound that result in cancer cell death in uveal melanoma. Drug combinations of PAC-1 with the kinase inhibitor entrectinib have shown a synergistic effect against uveal melanoma cell lines. Specifically, PAC-1 and entrectinib are synergistic against wild-type and mutant uveal melanoma cell lines (e.g., GNAQ and GNA11).

    SELECTIVE APOPTOTIC INDUCTION IN CANCER CELLS INCLUDING ACTIVATION OF PROCASPASE-3
    6.
    发明申请
    SELECTIVE APOPTOTIC INDUCTION IN CANCER CELLS INCLUDING ACTIVATION OF PROCASPASE-3 审中-公开
    癌细胞中的选择性诱导诱导，包括细胞因子-3的激活

    公开(公告)号：WO2006128173A2

    公开(公告)日：2006-11-30

    申请号：PCT/US2006020910

    申请日：2006-05-26

    申请人： UNIV ILLINOIS ,  HERGENROTHER PAUL J ,  PUTT KARSON S ,  CHEN GRACE W ,  PEARSON JENNIFER M

    发明人： HERGENROTHER PAUL J ,  PUTT KARSON S ,  CHEN GRACE W ,  PEARSON JENNIFER M

    IPC分类号： A61K31/495

    CPC分类号： A61K31/495 ,  C07D295/15 ,  C12Q1/37 ,  G01N33/502 ,  G01N33/574 ,  G01N2333/96466 ,  G01N2510/00 ,  G01N2800/52

    摘要： Compounds and related methods for synthesis, and the use of compounds in therapy for the treatment of cancer and selective induction of apoptosis in cells are disclosed. Compounds are disclosed in connection with modification of procaspases such as procaspase-3, and particular embodiments are capable of direct activation of procaspase-3 and procaspase-7 to the effector forms of caspase-3 and caspase-7. Procaspase-3 levels can vary among cancer cell types; several types have relatively high levels and can have increased susceptibility to chemotherapy by compounds and methods herein. Therapeutic applications are relevant for a variety of cancer conditions and cell types, e.g. breast, lung, brain, colon, renal, adrenal, melanoma, and others.

    摘要翻译： 公开了合成的化合物和相关方法，以及化合物在治疗中用于治疗癌症和选择性诱导细胞凋亡的用途。 公开了与胱天蛋白酶（procaspase）如procaspase-3的修饰有关的化合物，特定实施方案能够将胱天蛋白酶-3和胱天蛋白酶-7的效应物形式直接活化于胱天蛋白酶-3和胱天蛋白酶-7。 Procaspase-3水平可能因癌细胞类型而异; 几种类型具有相对较高的水平，并且可以通过本文化合物和方法增加对化学疗法的易感性。 治疗应用与各种癌症状况和细胞类型有关，例如， 乳腺，肺，脑，结肠，肾，肾上腺，黑素瘤等。

    SMALL MOLECULE ACTIVATORS OF THE IMMUNE SYSTEM
    7.
    发明申请
    SMALL MOLECULE ACTIVATORS OF THE IMMUNE SYSTEM 审中-公开

    公开(公告)号：WO2023070071A2

    公开(公告)日：2023-04-27

    申请号：PCT/US2022/078484

    申请日：2022-10-21

    申请人： THE BOARD OF TRUSTEES OF THE UNIVERSITY OF ILLINOIS ,  HERGENROTHER, Paul J. ,  CHATKEWITZ, Lindsay

    发明人： HERGENROTHER, Paul J. ,  CHATKEWITZ, Lindsay

    IPC分类号： A61K31/56 ,  A61K31/565 ,  A61K31/568 ,  C07J73/00

    摘要： The technology disclosed herein provides (4aR,4bS,6aS,9aS,9bS)-1-(4-chlorobenzyl)-4a,6a-dimethyl-3,4,4a,6,6a,8,9,9a,9b,10-decahydro-1H-indeno[5,4-f]quinoline-2,5,7(4bH)-trione, identified as compound IB:10:D, and related compounds. Compound IB:10:D was discovered though screening a compound library for inhibitors of the enzyme SULT2B1b. This enzyme, which produces the product cholesterol sulfate, is overexpressed in cancer. The product acts as an immunosuppressant that results in suppression of the immune system's ability to clear tumor cells. Compounds related to IB:10:D were synthesized and shown to inhibit production of cholesterol sulfate. The discovered inhibitors of SULT2B1b provide new compounds and methods for immunotherapy and cancer treatment.