SGI-1776 free base
(Synonyms: SGI1776,SGI 1776) 目录号 : GC16497
SGI-1776 free base是一种ATP竞争性的Pim激酶抑制剂，可抑制Pim-1（IC50=7nM）、Pim-2（IC50=363nM）和Pim-3（IC50=69nM）的活性。
Cas No.:1025065-69-3
Sample solution is provided at 25 µL, 10mM.
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SGI-1776 free base is an ATP-competitive Pim kinase inhibitor that inhibits the activity of Pim-1 (IC50=7nM), Pim-2 (IC50=363nM), and Pim-3 (IC50=69nM)[1]. SGI-1776 free base can trigger apoptosis by inducing G1 phase cell cycle arrest, activating Caspase-3, and reducing Mcl-1 protein levels[2]. SGI-1776 free base exhibits anti-tumor activity[3]. SGI-1776 free base has the ability to regulate lipid metabolism[4].
In vitro, treatment of chronic lymphocytic leukemia (CLL) primary cells with SGI-1776 free base (3–10μM) for 24–72 hours significantly induces apoptosis and inhibits global RNA synthesis by suppressing Pim kinase activity and reducing c-Myc (Ser62) phosphorylation levels[5]. Treatment of salivary adenoid cystic carcinoma cells (SACC-83 and SACC-LM) with SGI-1776 free base (2.5–5μM) for 72 hours significantly inhibits cell proliferation and induces G0/G1 and G2/M phase cell cycle arrest by suppressing Pim-1 protein expression and kinase activity. SGI-1776 free base reduces cell migration and invasion capabilities, induces mitochondrial membrane potential depolarization and caspase-3 activation, and promotes apoptosis[6].
In vivo, oral administration of SGI-1776 free base (75mg/kg) daily, five times per week for three weeks, to BALB/c-nu nude mice bearing ARK1 subcutaneous xenograft tumors significantly inhibits tumor growth[7]. Intraperitoneal injection of SGI-1776 free base (5mg/kg) once weekly, starting from 6 weeks of age, in wild-type or Ifnar1-/- C57BL/6 mice significantly suppresses Zika virus (ZIKV) replication in peritoneal macrophages of both mouse strains[8].
References:
[1] Chen LS, Redkar S, Taverna P, et al. Mechanisms of cytotoxicity to Pim kinase inhibitor, SGI-1776, in acute myeloid leukemia. Blood. 2011 Jul 21;118(3):693-702.
[2] Zhang X, Song M, Kundu JK, et al. PIM Kinase as an Executional Target in Cancer. J Cancer Prev. 2018 Sep;23(3):109-116.
[3] Yang Q, Chen LS, Neelapu SS, et al. Combination of Pim kinase inhibitor SGI-1776 and bendamustine in B-cell lymphoma. Clin Lymphoma Myeloma Leuk. 2013 Sep;13 Suppl 2(0 2):S355-62.
[4] Park YK, Hong VS, Lee TY, et al. The novel anti-adipogenic effect and mechanisms of action of SGI-1776, a Pim-specific inhibitor, in 3T3-L1 adipocytes. Int J Mol Med. 2016 Jan;37(1):157-64.
[5] Chen LS, Redkar S, Bearss D, et al. Pim kinase inhibitor, SGI-1776, induces apoptosis in chronic lymphocytic leukemia cells. Blood. 2009 Nov 5;114(19):4150-7.
[6] Hou X, Yu Y, Feng J, et al. Biochemical changes of salivary gland adenoid cystic carcinoma cells induced by SGI-1776. Exp Cell Res. 2017 Mar 15;352(2):403-411.
[7] Takeuchi H, Miyamoto T, Fuseya C, et al. PIM1 is a Poor Prognostic Factor for and Potential Therapeutic Target in Serous Carcinoma of the Endometrium. Int J Gynecol Pathol. 2023 May 1;42(3):282-292.
[8] Ren Y, Liu Y, Pang R, et al. ZIKV prM hijacks PIM1 kinase for phosphorylation to prevent ubiquitin-mediated degradation and facilitate viral replication. Front Cell Infect Microbiol. 2024 Nov 29;14:1502770.
SGI-1776 free base是一种ATP竞争性的Pim激酶抑制剂，可抑制Pim-1（IC50=7nM）、Pim-2（IC50=363nM）和Pim-3（IC50=69nM）的活性[1]。SGI-1776 free base可通过诱导G1期细胞周期停滞、激活Caspase-3以及降低Mcl-1蛋白水平来触发细胞凋亡[2]。SGI-1776 free base具有抗肿瘤活性[3]。SGI-1776 free base还具有调节脂肪代谢的能力[4]。
在体外，SGI-1776 free base（3–10μM）处理慢性淋巴细胞白血病（CLL）原代细胞24–72小时，SGI-1776 free base通过抑制Pim激酶活性及降低c-Myc（Ser62）磷酸化水平，显著诱导细胞凋亡并抑制全局RNA合成 [5]。SGI-1776 free base（2.5–5μM）处理唾液腺腺样囊性癌细胞（SACC-83及SACC-LM）72小时，SGI-1776 free base通过抑制Pim-1蛋白表达及激酶活性，显著抑制细胞增殖并诱导G0/G1期和G2/M期周期阻滞。SGI-1776 free base可降低细胞迁移和侵袭能力，诱导线粒体膜电位去极化及caspase-3活化，并促进细胞凋亡[6]。
在体内，SGI-1776 free base（75 mg/kg）每日口服给药，每周5次，持续3周，处理携带ARK1皮下异种移植瘤的BALB/c-nu裸鼠，SGI-1776 free base显著抑制肿瘤生长[7]。SGI-1776 free base（5mg/kg）每周一次腹腔注射，用于处理6周龄开始的野生型或Ifnar1-/- C57BL/6小鼠。SGI-1776显著抑制了ZIKV病毒在两种小鼠的腹腔巨噬细胞中的复制[8]。
| Cell experiment [1]: | |
Cell lines | ARK1, ARK2, and SPAC1L cells (human uterine serous carcinoma cell lines) |
Preparation Method | SC cell lines were cultured in RPMI 1640 medium supplemented with 10% FBS at 37°C, 5% CO₂. Cells were treated with the PIM1 inhibitor SGI-1776 free base at various concentrations (1-10μM). |
Reaction Conditions | 1-10μM; Duration varied by assay (viability: 4 days, migration: 8h, invasion: 20h) |
Applications | SGI-1776 free base significantly inhibits cell proliferation and induces G0/G1 and G2/M phase cell cycle arrest by suppressing Pim-1 protein expression and kinase activity. SGI-1776 free base reduces cell migration and invasion capabilities, induces mitochondrial membrane potential depolarization and caspase-3 activation, and promotes apoptosis |
| Animal experiment [2]: | |
Animal models | BALB/c-nu nude mice |
Preparation Method | Subcutaneous xenografts were established by injecting ARK1 cells (human salivary adenoid cystic carcinoma cell line) into the flanks of mice. Once tumors reached ~5mm in diameter, mice were orally administered SGI-1776 free base (75mg/kg). |
Dosage form | 75mg/kg; oral gavage |
Applications | Oral administration of SGI-1776 free base significantly suppressed the growth of ARK1 xenograft tumors compared to the solvent control group, as measured by tumor volume and weight, without impairing the general health or body weight of the mice. |
References: | |
| Cas No. | 1025065-69-3 | SDF | |
| 别名 | SGI1776,SGI 1776 | ||
| 化学名 | N-[(1-methylpiperidin-4-yl)methyl]-3-[3-(trifluoromethoxy)phenyl]imidazo[1,2-b]pyridazin-6-amine | ||
| Canonical SMILES | CN1CCC(CC1)CNC2=NN3C(=NC=C3C4=CC(=CC=C4)OC(F)(F)F)C=C2 | ||
| 分子式 | C20H22F3N5O | 分子量 | 405.42 |
| 溶解度 | ≥ 40.5 mg/mL in DMSO, ≥ 101 mg/mL in EtOH | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.4666 mL | 12.3329 mL | 24.6658 mL |
| 5 mM | 493.3 μL | 2.4666 mL | 4.9332 mL |
| 10 mM | 246.7 μL | 1.2333 mL | 2.4666 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
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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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