Design, synthesis, and pharmacological evaluation of bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide 3 (BPTES) analogs as glutaminase inhibitors.
Design, synthesis, and pharmacological evaluation of bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide 3 (BPTES) analogs as glutaminase inhibitors.
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DOI：
10.1021/jm301191p
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发表时间：
2012-12-13
影响因子：
7.3
通讯作者：
Tsukamoto, Takashi
中科院分区：
文献类型：
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作者：
Shukla, Krupa;Ferraris, Dana V.;Thomas, Ajit G.;Stathis, Marigo;Duvall, Bridget;Delahanty, Greg;Alt, Jesse;Rais, Rana;Rojas, Camilo;Gao, Ping;Xiang, Yan;Dang, Chi V.;Slusher, Barbara S.;Tsukamoto, Takashi
双-2-（5-苯基乙酰氨基-1,2,4-噻二唑-2-基）乙硫醚（BPTES）是一种有效的选择性肾型谷氨酰胺酶（GLS）变甾抑制剂，已被用作确定GLS抑制治疗潜力的分子探针。为了鉴定更有效的GLS抑制剂，并改进药物样分子特性，我们合成并评估了一系列BPTES类似物。我们的构效关系（SAR）研究表明，一些截断的类似物保留了BPTES的效力，这为改善其水溶性提供了机会。其中一种类似物N-（5-{2-[2-（5-氨基-[1,3,4]噻二唑-2-基）-乙基磺胺]-乙基}-[1,3,4]噻二唑-2-基）-2-苯基-乙酰胺相对于BPTES具有相似的效价和更好的溶解度，并在体外和小鼠异种移植模型中减弱了P493人淋巴瘤B细胞的生长。
Bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide (BPTES) is a potent and selective allosteric inhibitor of kidney-type glutaminase (GLS) that has served as a molecular probe to determine the therapeutic potential of GLS inhibition. In an attempt to identify more potent GLS inhibitors with improved drug-like molecular properties, a series of BPTES analogs were synthesized and evaluated. Our structure-activity relationship (SAR) studies revealed that some truncated analogs retained the potency of BPTES, presenting an opportunity to improve its aqueous solubility. One of the analogs, N-(5-{2-[2-(5-amino-[1,3,4]thiadiazol-2-yl)-ethylsulfanyl]-ethyl}-[1,3,4]thiadiazol-2-yl)-2-phenyl-acetamide, exhibited similar potency and better solubility relative to BPTES and attenuated the growth of P493 human lymphoma B cells in vitro as well as in a mouse xenograft model.
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影响因子：
--
作者：
Erickson JW;Cerione RA
通讯作者：
Cerione RA
DOI：
10.1016/s0169-328x(99)00331-9
发表时间：
2000-03-10
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Holcomb, T;Taylor, L;Curthoys, NP
通讯作者：
Curthoys, NP
影响因子：
11.2
作者：
Seltzer MJ;Bennett BD;Joshi AD;Gao P;Thomas AG;Ferraris DV;Tsukamoto T;Rojas CJ;Slusher BS;Rabinowitz JD;Dang CV;Riggins GJ
通讯作者：
Riggins GJ
影响因子：
64.8
作者：
Gao, Ping;Tchernyshyov, Irina;Chang, Tsung-Cheng;Lee, Yun-Sil;Kita, Kayoko;Ochi, Takafumi;Zeller, Karen I.;De Marzo, Angelo M.;Van Eyk, Jennifer E.;Mendell, Joshua T.;Dang, Chi V.
通讯作者：
Dang, Chi V.
影响因子：
29
作者：
Le A;Lane AN;Hamaker M;Bose S;Gouw A;Barbi J;Tsukamoto T;Rojas CJ;Slusher BS;Zhang H;Zimmerman LJ;Liebler DC;Slebos RJ;Lorkiewicz PK;Higashi RM;Fan TW;Dang CV
通讯作者：
Dang CV