- A structure—activity relationship study of bis-benzamides as inhibitors of androgen receptor—coactivator interaction
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The interaction between androgen receptor (AR) and coactivator proteins plays a critical role in AR-mediated prostate cancer (PCa) cell growth, thus its inhibition is emerging as a promising strategy for PCa treatment. To develop potent inhibitors of the
- Lee, Tae-Kyung,Ravindranathan, Preethi,Sonavane, Rajni,Raj, Ganesh V.,Ahn, Jung-Mo
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supporting information
(2019/08/07)
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- Preparation method of oxybuprocaine hydrochloride
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The invention discloses a preparation method of oxybuprocaine hydrochloride. The preparation method includes following steps: in the presence of alkali I, subjecting 3-hydroxy-4-ethyl nitrobenzoate and bromobutane to electrophilic substitution reaction to obtain 3-butoxy-4-ethyl nitrobenzoate; under alkaline condition, enabling 3-butoxy-4-ethyl nitrobenzoate to be in hydrolysis reaction, and adjusting pH value of a system after hydrolysis reaction to 1-3 to obtain 3-butoxy-4-nitrobenzoic acid; in the presence of alkali II, subjecting the 3-butoxy-4-nitrobenzoic acid and diethylamino ethyl chloride to electrophilic substitution reaction to obtain 4-nitro-2-butoxy nitrobenzoic acid-2-(diethylamino) ethyl ester, and subjecting the 4-nitro-2-butoxy nitrobenzoic acid-2-(diethylamino) ethyl ester to reduction reaction under action of ferric trichloride and hydrazine hydrate to obtain oxybuprocaine hydrochloride. 3-hydroxy-4-ethyl nitrobenzoate is adopted as a raw material to obtain a target product through four steps of conventional reaction; each step of reaction does not need high-pressure condition, and needed raw materials are all conventional compounds, so that the preparation method is easy to obtain and low in cost.
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Paragraph 0042; 0043; 0053; 0054
(2017/08/31)
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- Estrogen receptor coregulator binding modulators (ERXs) effectively target estrogen receptor positive human breast cancers
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The majority of human breast cancer is estrogen receptor alpha (ER) positive. While anti-estrogens/aromatase inhibitors are initially effective, resistance to these drugs commonly develops. Therapy-resistant tumors often retain ER signaling, via interaction with critical oncogenic coregulator proteins. To address these mechanisms of resistance, we have developed a novel ER coregulator binding modulator, ERX-11. ERX-11 interacts directly wiTheR and blocks the interaction between a subset of coregulators with both native and mutant forms of ER. ERX-11 effectively blocks ER-mediated oncogenic signaling and has potent anti-proliferative activity against therapy-sensitive and therapy-resistant human breast cancer cells. ERX-11 is orally bioavailable, with no overt signs of toxicity and potent activity in both murine xenograft and patient-derived breast tumor explant models. This first-in-class agent, with its novel mechanism of action of disrupting critical protein-protein interactions, overcomes the limitations of current therapies and may be clinically translatable for patients with therapy-sensitive and therapy-resistant breast cancers.
- Raj, Ganesh V.,Sareddy, Gangadhara Reddy,Ma, Shihong,Lee, Tae-Kyung,Viswanadhapalli, Suryavathi,Li, Rui,Liu, Xihui,Murakami, Shino,Chen, Chien-Cheng,Lee, Wan-Ru,Mann, Monica,Krishnan, Samaya Rajeshwari,Manandhar, Bikash,Gonugunta, Vijay K.,Strand, Douglas,Tekmal, Rajeshwar Rao,Ahn, Jung-Mo,Vadlamudi, Ratna K.
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supporting information
(2017/09/18)
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