116-9e
(Synonyms: MAL2-11B) 目录号 : GC63796116-9e 是 Hsp40-Hsp70 结合的阻断剂,从而抑制 Hsp70-Hsp40 的伴侣活性。Hsp40 家族的辅助伴侣通过一个保守的 J 结构域与 Hsp70 结合。116-9e 通过阻止 Hsp70-Hsp40 复合物组装来抑制伴侣功能。
Cas No.:831217-43-7
Sample solution is provided at 25 µL, 10mM.
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116-9e (MAL2-11B) is a Hsp70 co-chaperone DNAJA1 inhibitor. 116-9e inhibits Simian Virus 40 (SV40) replication and DNA synthesis. 116-9e inhibits tumor antigen (TAg)’s endogenous ATPase activity and the TAg-mediated activation of Hsp70[1][2].
116-9e (MAL2-11B) inhibits TAg stimulation of Hsp70 with greater efficacy than MAL3-101, significantly reduces viral replication and DNA synthesis. MAL2-11B also inhibits the activity of the TAg ATPase domain[1]. 116-9e (MAL2-11B; 15 µM; 5 days) significantly reduces the growth of BK virus in a human kidney cell line[1].
[1]. Christine M Wright, et al. Inhibition of Simian Virus 40 replication by targeting the molecular chaperone function and ATPase activity of T antigen. Virus Res. 2009 Apr;141(1):71-80.
[2]. Nitika, et al. Chemogenomic screening identifies the Hsp70 co-chaperone DNAJA1 as a hub for anticancer drug resistance. Sci Rep. 2020 Aug 14;10(1):13831.
Cas No. | 831217-43-7 | SDF | Download SDF |
别名 | MAL2-11B | ||
分子式 | C31H32N2O5 | 分子量 | 512.6 |
溶解度 | DMSO : 100 mg/mL (195.08 mM; Need ultrasonic) | 储存条件 | Store at -20°C |
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1 mg | 5 mg | 10 mg | |
1 mM | 1.9508 mL | 9.7542 mL | 19.5084 mL |
5 mM | 0.3902 mL | 1.9508 mL | 3.9017 mL |
10 mM | 0.1951 mL | 0.9754 mL | 1.9508 mL |
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1. 首先保证母液是澄清的;
2.
一定要按照顺序依次将溶剂加入,进行下一步操作之前必须保证上一步操作得到的是澄清的溶液,可采用涡旋、超声或水浴加热等物理方法助溶。
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The Hsp70 co-chaperone Ydj1/HDJ2 regulates ribonucleotide reductase activity
PLoS Genet 2018 Nov 19;14(11):e1007462.PMID:30452489DOI:10.1371/journal.pgen.1007462.
Hsp70 is a well-conserved molecular chaperone involved in the folding, stabilization, and eventual degradation of many "client" proteins. Hsp70 is regulated by a suite of co-chaperone molecules that assist in Hsp70-client interaction and stimulate the intrinsic ATPase activity of Hsp70. While previous studies have shown the anticancer target ribonucleotide reductase (RNR) is a client of Hsp70, the regulatory co-chaperones involved remain to be determined. To identify co-chaperone(s) involved in RNR activity, 28 yeast co-chaperone knockout mutants were screened for sensitivity to the RNR-perturbing agent Hydroxyurea. Ydj1, an important cytoplasmic Hsp70 co-chaperone was identified to be required for growth on HU. Ydj1 bound the RNR subunit Rnr2 and cells lacking Ydj1 showed a destabilized RNR complex. Suggesting broad conservation from yeast to human, HDJ2 binds R2B and regulates RNR stability in human cells. Perturbation of the Ssa1-Ydj1 interaction through mutation or Hsp70-HDJ2 via the small molecule 116-9e compromised RNR function, suggesting chaperone dependence of this novel role. Mammalian cells lacking HDJ2 were significantly more sensitive to RNR inhibiting drugs such as hydroxyurea, gemcitabine and triapine. Taken together, this work suggests a novel anticancer strategy-inhibition of RNR by targeting Hsp70 co-chaperone function.
Chemogenomic screening identifies the Hsp70 co-chaperone DNAJA1 as a hub for anticancer drug resistance
Sci Rep 2020 Aug 14;10(1):13831.PMID:32796891DOI:10.1038/s41598-020-70764-x.
Heat shock protein 70 (Hsp70) is an important molecular chaperone that regulates oncoprotein stability and tumorigenesis. However, attempts to develop anti-chaperone drugs targeting molecules such as Hsp70 have been hampered by toxicity issues. Hsp70 is regulated by a suite of co-chaperone molecules that bring "clients" to the primary chaperone for efficient folding. Rather than targeting Hsp70 itself, here we have examined the feasibility of inhibiting the Hsp70 co-chaperone DNAJA1 as a novel anticancer strategy. We found DNAJA1 to be upregulated in a variety of cancers, suggesting a role in malignancy. To confirm this role, we screened the NIH Approved Oncology collection for chemical-genetic interactions with loss of DNAJA1 in cancer. 41 compounds showed strong synergy with DNAJA1 loss, whereas 18 dramatically lost potency. Several hits were validated using a DNAJA1 inhibitor (116-9e) in castration-resistant prostate cancer cell (CRPC) and spheroid models. Taken together, these results confirm that DNAJA1 is a hub for anticancer drug resistance and that DNAJA1 inhibition is a potent strategy to sensitize cancer cells to current and future therapeutics. The large change in drug efficacy linked to DNAJA1 suggests a personalized medicine approach where tumor DNAJA1 status may be used to optimize therapeutic strategy.