SBI-0206965 |
Catalog No.GC15654
One-Click Copy Product Info
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SBI-0206965 es un inhibidor ULK1 de autofagia quinasa potente, selectivo y permeable a las células con IC50 de 108 nM para la quinasa ULK1 y 711 nM para la quinasa altamente relacionada ULK2.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1884220-36-3
Sample solution is provided at 25 µL, 10mM.
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SBI-0206965 , el derivado de la pirimidina, es un inhibidor de la quinasa ULK1 altamente selectivo con un valor de IC50 de 108nM[1]. SBI-0206965 fue reportado como un inhibidor de moléculas pequeñas de la quinasa ULK2 , que tiene un valor de IC50 como 711nM[2]. SBI-0206965 también puede inhibir AMPK[3].
SBI-0206965 (25μM , 3h) inhibió modestamente la señalización de AMPK en los miotubos C2C12, pero también inhibió la señalización de insulina, la absorción de glucosa mediada por insulina/independiente de AMPK[4]. SBI-0206965 (10μM , 40min) tiene un efecto inhibidor no específico fuera del objetivo.
En el transporte de glucosa muscular [2]. SBI-0206965 ( 8μmol/L , 1h) hipoxia invertida/
Muerte celular y piroptosis inducida por reoxygenation (H/R) en cardiomyocytes[5] .
SBI-0206965 (50mg/kg ; 3 días , 9 vece en 30 días ; inyección intraperitoneal) desencadenó la apoptosis al prevenir la autofagia y el flujo de la vía de fosfato de pentosa (PPP) flux[6] . SBI-0206965 ( 5 o 50μM ; 2.5h ; inyecciiones intravítreaa, imágenes vivas del nervio óptico) protege contra la degeneración axonal aguda (AAD) después del aplastamiento del nervio óptico de rata in vivo[7] .
SBI-0206965 suprimió el 5-aminoimidazole-4-carboxamideribo nucleótido (AICAR) estimuló el transporte de glucosa tanto en el extensor digitorum longus como en el músculo soleo [2] .
References:
[1] CHEN Y, XIE X, WANG C, et al. Dual targeting of NUAK1 and ULK1 using the multitargeted inhibitor MRT68921 exerts potent antitumor activities [J]. Cell Death Dis, 2020, 11(8): 712.
[2] KNUDSEN J R, MADSEN A B, PERSSON K W, et al. The ULK1/2 and AMPK Inhibitor SBI-0206965 Blocks AICAR and Insulin-Stimulated Glucose Transport [J]. Int J Mol Sci, 2020, 21(7):
[3] DITE T A, LANGENDORF C G, HOQUE A, et al. AMP-activated protein kinase selectively inhibited by the type II inhibitor SBI-0206965 [J]. J Biol Chem, 2018, 293(23): 8874-85.
[4] AHWAZI D, NEOPANE K, MARKBY G R, et al. Investigation of the specificity and mechanism of action of the ULK1/AMPK inhibitor SBI-0206965 [J]. Biochem J, 2021, 478(15): 2977-97.
[5] DENG L, JIANG L, WEI N, et al. Anesthetic sevoflurane simultaneously regulates autophagic flux and pyroptotic cell death-associated cellular inflammation in the hypoxic/re-oxygenated cardiomyocytes: Identification of sevoflurane as putative drug for the treatment of myocardial ischemia-reperfusion injury [J]. Eur J Pharmacol, 2022, 936(175363.
[6] LU J, ZHU L, ZHENG L P, et al. Overexpression of ULK1 Represents a Potential Diagnostic Marker for Clear Cell Renal Carcinoma and the Antitumor Effects of SBI-0206965 [J]. EBioMedicine, 2018, 34(85-93.
[7] VAHSEN B F, RIBAS V T, SUNDERMEYER J, et al. Inhibition of the autophagic protein ULK1 attenuates axonal degeneration in vitro and in vivo, enhances translation, and modulates splicing [J]. Cell Death Differ, 2020, 27(10): 2810-27.
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Cell experiment[1]: |
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Cell lines |
Murine embryonic fibroblast cells ( soleus and extensor digitorum longus muscles) |
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Preparation method |
Los músculos del soleo y el extensor digitorum longus fueron extirpar de ratones. Las células se suspendieron en cámaras de incubación que contenían 30℃ de tampón de Krebs Ringer Henseleit (KRH) suplementado con manitol de 8 mM y piruvato de 2 m. Los músculos fueron preincubados durante 40 minutos con 10 μM SBI-0206965, y posteriormente estimulados con o sin insulina a 60 nM durante 20 minutos. La duración total de los experimentos de incubación fue de 1 hora. |
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Reaction Conditions |
10μM ; 40min |
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Applications |
Aplicaciones SBI-0206965 tiene un efecto inhibidor no específico fuera del objetivo en el transporte muscular de glucosa. |
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Animal experiment[2]: |
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Animal models |
Ratones desnudos BALB/c macho |
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Preparation method |
Se inyectaron células A498 (5×106) suspendidas en 100 μL de PBS/Matrigel (1:1) en el flanco posterior de los ratones. Después de 14 días de implantación, los ratones se dividieron aleatoriamente en dos grupos con 6 ratones en cada grupo. A los ratones se les inyectó por vía intraperitoneal SBI-0206965 en DMSO (50 mg/kg/d) cada 3 días por un total de nueve veces durante un período de 30 días. |
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Dosage form |
50 mg/kg; inyectado por vía intraperitoneal con SBI-0206965; 30 días |
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Applications |
SBI-0206965 bloquea la actividad de la quinasa ULK1 que resultó en un nivel de efecto anticancerígeno in vivo. |
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References: [1] KNUDSEN J R, MADSEN A B, PERSSON K W, et al. The ULK1/2 and AMPK Inhibitor SBI-0206965 Blocks AICAR and Insulin-Stimulated Glucose Transport [J]. Int J Mol Sci, 2020, 21(7): [2] LU J, ZHU L, ZHENG L P, et al. Overexpression of ULK1 Represents a Potential Diagnostic Marker for Clear Cell Renal Carcinoma and the Antitumor Effects of SBI-0206965 [J]. EBioMedicine, 2018, 34(85-93. |
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| Cas No. | 1884220-36-3 | SDF | |
| Chemical Name | (Z)-2-((5-bromo-2-((3,4,5-trimethoxyphenyl)amino)pyrimidin-4-yl)oxy)-N-methylbenzimidic acid | ||
| Canonical SMILES | C/N=C(O)/C1=CC=CC=C1OC2=NC(NC3=CC(OC)=C(OC)C(OC)=C3)=NC=C2Br | ||
| Formula | C21H21BrN4O5 | M.Wt | 489.32 |
| Solubility | ≥ 24.5mg/mL in DMSO | 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. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.0437 mL | 10.2183 mL | 20.4365 mL |
| 5 mM | 408.7 μL | 2.0437 mL | 4.0873 mL |
| 10 mM | 204.4 μL | 1.0218 mL | 2.0437 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
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.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 6 reference(s) in Google Scholar.)