- TREATMENT OF METASTASIZED ESTROGEN RECEPTOR POSITIVE BREAST CANCER
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A treatment method comprising a small molecule ERα biomodulator that kills therapy- resistant ERα cancer that metastasized to the brain is disclosed. In one embodiment, the small molecule biomodulator has increased therapeutic utility because of an increased ability to kill therapy-resistant breast cancer cells that metastasized to the brain compared to BHPI and other conventional therapies (endocrine therapies, tamoxifen and fulvestrant/TCI). The small molecule biomodulators not only inhibit proliferation of the cancer cells but kills them, which prevents reactivation of tumors years later.
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Page/Page column 40; 43
(2022/02/05)
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- COMPOUNDS FOR ESTROGEN RECEPTOR POSITIVE CANCERS
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Small molecule ERα biomodulators that kill therapy -resistant ERα positive breast, ovarian, and endometrial cancer cells are disclosed. In one embodiment, the small molecule biomodulator has increased therapeutic utility because of an increased ability to kill therapy- resistant breast cancer cells compared to BHPI and other conventional therapies (endocrine therapies, tamoxifen and fulvestrant/ICI). The small molecule biomodulators not only inhibit proliferation of the cancer cells but kills them, which prevents reactivation of tumors years later.
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Paragraph 0118; 0122-0123
(2021/11/06)
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- ACTIVATORS OF THE UNFOLDED PROTEIN RESPONSE
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A set of small molecules ERα biomodulators that kill therapy-resistant ERα positive breast, ovarian, and endometrial cancer cells. These small molecules have increased therapeutic potential because of an increased ability to kill therapy-resistant breast cancer cells compared to BHPI and other conventional therapies (endocrine therapies, tamoxifen and fulvestrant/ICI). The new compounds do not only inhibit proliferation of the cancer cells but actually kills them, which prevents reactivation of tumors years later.
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Page/Page column 30; 44; 45
(2020/01/31)
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- Design, synthesis, and biological evaluation of (2E)-(2-oxo-1, 2-dihydro-3H-indol-3-ylidene)acetate derivatives as anti-proliferative agents through ROS-induced cell apoptosis
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A novel class of (2E)-(2-oxo-1, 2-dihydro-3H-indol-3-ylidene)acetate derivatives were designed and synthesized as potent anti-proliferative agents. Most of these compounds showed potent anti-proliferative activity against some tumor cell lines, including SK-BR-3, MDA-MB-231, HCT-116, SW480, Ovcar-3, HL-60, Saos-2 and HepG2. Compounds 8c and 11h were identified as the most potent ones, while HL-60, HCT116 and MDA-MB-231 were the most sensitive cell lines. Mechanistic study revealed that compound 8c enhanced reactive oxygen species level by inhibiting TrxR and then induced apoptosis by activating apoptosis proteins, bax and cleaved-caspase 3 in HCT116?cells. Preliminary SAR analysis indicated that modifications of the double bond and ester group made great effects on the anti-proliferative activity. Our findings suggested that it was worth further studies on the antitumor potency of (2E)-(2-oxo-1, 2-dihydro-3H-indol-3-ylidene)acetates.
- Song, Zhuang,Chen, Cai-Ping,Liu, Jun,Wen, Xiaoan,Sun, Hongbin,Yuan, Haoliang
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p. 809 - 819
(2016/09/23)
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- Potent Synergy between Spirocyclic Pyrrolidinoindolinones and Fluconazole against Candida albicans
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A spiroindolinone, (1S,3R,3aR,6aS)-1-benzyl-6′-chloro-5-(4-fluorophenyl)-7′-methylspiro[1,2,3a,6a-tetrahydropyrrolo[3,4-c]pyrrole-3,3′-1H-indole]-2′,4,6-trione, was previously reported to enhance the antifungal effect of fluconazole against Candida albicans. A diastereomer of this compound was synthesized, along with various analogues. Many of the compounds were shown to enhance the antifungal effect of fluconazole against C. albicans, some with exquisite potency. One spirocyclic piperazine derivative, which we have named synazo-1, was found to enhance the effect of fluconazole with an EC50 value of 300 pM against a susceptible strain of C. albicans and going as low as 2 nM against some resistant strains. Synazo-1 exhibits true synergy with fluconazole, with an FIC index below 0.5 in the strains tested. Synazo-1 exhibited low toxicity in mammalian cells relative to the concentrations required for antifungal synergy. Synergy from stereochemical complexity: An attempt to synthesize analogues of a known spiroindolinone led to a series of diastereomers. One spiroindolinone, termed synazo-1, was shown to exhibit potent activity (300 pM) against C. albicans in the presence of fluconazole. Synazo-1 is a true synergizer and was also highly active against some drug-resistant C. albicans strains.
- Premachandra, Ilandari Dewage Udara Anulal,Scott, Kevin A.,Shen, Chengtian,Wang, Fuqiang,Lane, Shelley,Liu, Haoping,Van Vranken, David L.
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p. 1672 - 1686
(2015/10/06)
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- HYDRAZIDE COMPOUND AND PESTICIDAL USE OF THE SAME
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A hydrazide compound represented by the formula (1): has excellent pesticidal activity.
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Page/Page column 549
(2008/06/13)
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- DIPHENYL OX-INDOL-2-ON COMPOUNDS AND THEIR USE IN THE TREATMENT OF CANCER
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The present invention relates to substituted 3,3-diphenyl-1,3-dihydro-indol-2-one compounds, and the use of such compounds for the preparation of a medicament for the treatment of cancer in a mammal. It is postulated that treatment of cancers in which inh
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Page/Page column 35-36
(2010/02/14)
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- Potential Antitumor Agents. 61. Structure-Activity Relationships for in Vivo Colon 38 Activity among Disubstituted 9-Oxo-9H-xanthene-4-acetic Acids
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Analogues of 9-oxo-9H-xanthene-4-acetic acid (XAA) bearing small, lipophilic 5-substituents are among the most dose-potent compounds yet reported with the capability of causing hemorrhagic necrosis of implanted colon 38 tumors in mice.To further extend structure-activity relationships among this class of compound, a series of XAA derivatives bearing two small lipophilic groups at various positions have been prepared and evaluated.The 5,6-disubstituted compounds in particular show consistently high levels of both dose potency and activity, suggesting this is the optimal configuration among substituted 9-oxo-9H-xanthene-4-acetic acids.The 5,6-dimethyl and 5-methyl-6-methoxy are the most effective analogues, showing in vivo colon 38 activity comparable to that of FAA at 10-15-fold lower doses and superior activity to FAA at the respective optimal doses, and the former has been selected for detailed evaluation.
- Rewcastle, Gordon W.,Atwell, Graham J.,Zhuang, Li,Baguley, Bruce C.,Denny, William A.
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p. 217 - 222
(2007/10/02)
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