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BBT594

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Chemical Structure| 882405-89-2 同义名 : NVP-BBT594
CAS号 : 882405-89-2
货号 : A984305
分子式 : C28H30F3N7O3
纯度 : 99%+
分子量 : 569.578
MDL号 : MFCD30533519
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 35 mg/mL(61.45 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 The receptor tyrosine kinase RET (REarranged during Transfection) is activated by its ligand glial-derived neurotrophic factor (GDNF). RET signalling is involved in a diverse range of developmental processes including proliferation, migration survival and/or differentiation[3]. BBT594 is a potent RET inhibitor, used for cancer treatment. In human breast cancer MCF7 cells, BBT594 showed the highest suppression of GDNF-induced RET signaling, as assessed by RET, ERK1/2, AKT and ER phosphorylation, compared with sunitinib and cabozantinib. BBT594 treatment ranging in 0-1000 nM blocked the GDNF-mediated enhancement of MCF7-LTED cell viability in 2D culture and 3D colony formation[4]. 100 nM of BBT594 remarkably elevated the antiproliferative effects of letrozole in MCF7-2A cells[5]. BBT594 also acts as type II JAK inhibitor. BBT594 (1 μM, 48h) alone or combined with rapamycin (0.2 μM)/AZD2014 (0.2 μM) induced modest cell apoptosis in 2 P2RY8-CRLF2 samples (CRLF2-re and JAK2 mutation) and significant cell death in IGH-CRLF2 sample ex vivo[6].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.76mL

0.35mL

0.18mL

8.78mL

1.76mL

0.88mL

17.56mL

3.51mL

1.76mL
参考文献

[1]Andreucci E, Francica P, et al. Targeting the receptor tyrosine kinase RET in combination with aromatase inhibitors in ER positive breast cancer xenografts. Oncotarget. 2016 Dec 6;7(49):80543-80553.

[2]Morandi A, Martin LA, et al. GDNF-RET signaling in ER-positive breast cancers is a key determinant of response and resistance to aromatase inhibitors. Cancer Res. 2013 Jun 15;73(12):3783-95.

[3]Perea D, Guiu J, Hudry B, Konstantinidou C, Milona A, Hadjieconomou D, Carroll T, Hoyer N, Natarajan D, Kallijärvi J, Walker JA, Soba P, Thapar N, Burns AJ, Jensen KB, Miguel-Aliaga I. Ret receptor tyrosine kinase sustains proliferation and tissue maturation in intestinal epithelia. EMBO J. 2017 Oct 16;36(20):3029-3045. doi: 10.15252/embj.201696247. Epub 2017 Sep 12. PMID: 28899900; PMCID: PMC5641678.

[4]Andreucci E, Francica P, Fearns A, Martin LA, Chiarugi P, Isacke CM, Morandi A. Targeting the receptor tyrosine kinase RET in combination with aromatase inhibitors in ER positive breast cancer xenografts. Oncotarget. 2016 Dec 6;7(49):80543-80553. doi: 10.18632/oncotarget.11826. PMID: 27602955; PMCID: PMC5348339.

[5]Morandi A, Martin LA, Gao Q, Pancholi S, Mackay A, Robertson D, Zvelebil M, Dowsett M, Plaza-Menacho I, Isacke CM. GDNF-RET signaling in ER-positive breast cancers is a key determinant of response and resistance to aromatase inhibitors. Cancer Res. 2013 Jun 15;73(12):3783-95. doi: 10.1158/0008-5472.CAN-12-4265. Epub 2013 May 6. PMID: 23650283; PMCID: PMC3686594.

[6]Zhang Q, Shi C, Han L, Jain N, Roberts KG, Ma H, Cai T, Cavazos A, Tabe Y, Jacamo RO, Mu H, Zhao Y, Wang J, Wu SC, Cao F, Zeng Z, Zhou J, Mi Y, Jabbour EJ, Levine R, Tasian SK, Mullighan CG, Weinstock DM, Fruman DA, Konopleva M. Inhibition of mTORC1/C2 signaling improves anti-leukemia efficacy of JAK/STAT blockade in CRLF2 rearranged and/or JAK driven Philadelphia chromosome-like acute B-cell lymphoblastic leukemia. Oncotarget. 2018 Jan 17;9(8):8027-8041. doi: 10.18632/oncotarget.24261. PMID: 29487712; PMCID: PMC5814279.