Antimyeloma Effects of the Heat Shock Protein 70 Molecular Chaperone Inhibitor MAL3-101.
Antimyeloma Effects of the Heat Shock Protein 70 Molecular Chaperone Inhibitor MAL3-101.
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DOI：
10.1155/2011/232037
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发表时间：
2011
影响因子：
--
通讯作者：
Batuman O
中科院分区：
文献类型：
--
作者：
Braunstein MJ;Scott SS;Scott CM;Behrman S;Walter P;Wipf P;Coplan JD;Chrico W;Joseph D;Brodsky JL;Batuman O
多发性骨髓瘤（MM）是第二常见的血液系统恶性肿瘤，仍然无法治愈，主要是由于该疾病的治疗难治性/耐药性。面对这一令人信服的挑战，一种合理的方法是开发与现有有效药物协同作用的新药。这种方法将降低药物浓度，避免治疗耐药，并通过靶向MM中的新的和非冗余途径提高治疗效果。为了实现这一目标，我们研究了MAL3-101的抗骨髓瘤作用，MAL3-101是热休克蛋白（Hsp） 70分子伴侣的一类新的非atp位点抑制剂的成员。我们发现MAL3-101在体外和体内的异种移植物浆细胞瘤模型中对MM细胞系以及骨髓瘤患者的原发肿瘤细胞和骨髓内皮细胞具有抗骨髓瘤作用。与一种蛋白酶体抑制剂联合使用，MAL3-101显著增强了体外和体内抗骨髓瘤的作用。这些数据支持小分子抑制Hsp70功能的临床前理论，无论是单独使用还是与其他药物联合使用，都可以作为MM的有效治疗策略。
Multiple myeloma (MM) is the second most common hematologic malignancy and remains incurable, primarily due to the treatment-refractory/resistant nature of the disease. A rational approach to this compelling challenge is to develop new drugs that act synergistically with existing effective agents. This approach will reduce drug concentrations, avoid treatment resistance, and also improve treatment effectiveness by targeting new and nonredundant pathways in MM. Toward this goal, we examined the antimyeloma effects of MAL3-101, a member of a new class of non-ATP-site inhibitors of the heat shock protein (Hsp) 70 molecular chaperone. We discovered that MAL3-101 exhibited antimyeloma effects on MM cell lines in vitro and in vivo in a xenograft plasmacytoma model, as well as on primary tumor cells and bone marrow endothelial cells from myeloma patients. In combination with a proteasome inhibitor, MAL3-101 significantly potentiated the in vitro and in vivo antimyeloma effects. These data support a preclinical rationale for small molecule inhibition of Hsp70 function, either alone or in combination with other agents, as an effective therapeutic strategy for MM.
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乳腺癌进展中的热休克蛋白 - 适合治疗的病例？
DOI：
10.3109/02656736.2010.490254
发表时间：
2010
期刊：
International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group
影响因子：
--
作者：
Calderwood SK
通讯作者：
Calderwood SK
影响因子：
3.8
作者：
Braunstein M;Ozçelik T;Bağişlar S;Vakil V;Smith EL;Dai K;Akyerli CB;Batuman OA
通讯作者：
Batuman OA
DOI：
10.1073/pnas.92.5.1764
发表时间：
1995-02-28
影响因子：
11.1
作者：
KNITTLER, MR;DIRKS, S;HAAS, IG
通讯作者：
HAAS, IG
影响因子：
20.3
作者：
Catley, Laurence;Weisberg, Ellen;Anderson, Kenneth C.
通讯作者：
Anderson, Kenneth C.
影响因子：
45.3
作者：
Barlogie, B;Kyle, RA;Crowley, JC
通讯作者：
Crowley, JC