SGI-1776 free base (Synonyms: SGI1776,SGI 1776) |
| カタログ番号GC16497 |
Pimキナーゼの強力な阻害剤
Products are for research use only. Not for human use. We do not sell to patients.
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.
| 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 | |
| 同義語 | SGI1776,SGI 1776 | ||
| Chemical Name | 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 | ||
| Formula | C20H22F3N5O | M.Wt | 405.42 |
| 溶解度 | ≥ 40.5 mg/mL in DMSO, ≥ 101 mg/mL in EtOH | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
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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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Quality Control & SDS
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- Purity: >99.00%
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Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
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