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Chemical Structure| 1884220-36-3 Chemical Structure| 1884220-36-3

Structure of SBI-0206965
CAS No.: 1884220-36-3

Chemical Structure| 1884220-36-3

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SBI-0206965 is a potent, selective, and cell-permeable ULK1 kinase inhibitor with IC50 values of 108 nM for ULK1 kinase and 711 nM for the closely related kinase ULK2.

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Product Details of SBI-0206965

CAS No. :1884220-36-3
Formula : C21H21BrN4O5
M.W : 489.32
SMILES Code : O=C(NC)C1=CC=CC=C1OC2=NC(NC3=CC(OC)=C(OC)C(OC)=C3)=NC=C2Br
MDL No. :MFCD29472244
InChI Key :NEXGBSJERNQRSV-UHFFFAOYSA-N
Pubchem ID :92044402

Safety of SBI-0206965

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Related Pathways of SBI-0206965

Hedgehog

Isoform Comparison

Biological Activity

Description
SBI-0206965 is identified as a potent and selective inhibitor of the autophagy kinase ULK1, showing cell permeability with an IC50 of 108 nM for ULK1 kinase. It also exhibits inhibition towards ULK2, although with lesser potency, having an IC50 of 711 nM[1].
Target
  • Autophagy

    ULK1, IC50:108 nM

    ULK2, IC50:711 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
keratinocytes 10 µM 24 hours inhibition of ULK1 significantly prevented NM-induced autophagy and restored cell viability PMC7829253
HEK293T cells 5 μM 24 hours To study the effect of SBI-0206965 on AMPK and TFEB phosphorylation, results showed that SBI-0206965 significantly reduced the phosphorylation of AMPK and TFEB. PMC8726606
hiPSC-CMs 5 μM 24 h SBI-0206965 abolished hypoxia-induced mitophagy PMC9542630
Primary rat cortical neurons 5 μM 30 minutes To investigate the effect of SBI-0206965 on the mTOR signaling pathway, results showed that SBI significantly increased the levels of p-mTOR. PMC7493890
HUVECs 4 μmol/L 48 hours To investigate how autophagy inhibition induces endothelial cell apoptosis through p53 activation under hypoxic and nutrient-deprived conditions, thereby optimizing tumor vascular structure and function. PMC11667230
MV4;11 5 μM 48 hours Induced apoptosis through caspase pathway activation PMC7212592
MOLM-13 5 μM 48 hours Induced apoptosis through caspase pathway activation PMC7212592
U937 5 μM 48 hours Induced apoptosis, but with weaker effect PMC7212592
A498 cells 5 μM, 10 μM, 20 μM 24 hours SBI-0206965 significantly increased the apoptosis rate in A498 cells and inhibited autophagy and PPP flux. PMC6116477
ACHN cells 5 μM, 10 μM, 20 μM 24 hours SBI-0206965 significantly increased the apoptosis rate in ACHN cells and inhibited autophagy and PPP flux. PMC6116477
HaCaT keratinocytes 10 µM 24 hours Capsazepine inhibited NM-induced Ca2+ influx and CaMKKβ activation, thereby inhibiting AMPK and ULK1 activation, and ultimately suppressing NM-induced autophagy and cell death in keratinocytes. PMC7829253

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
rat rat calvarial defect model Negative pressure wound therapy (NPWT) 5 mg/kg Starting on the 8th day, lasting for one week To test the effect of negative pressure wound therapy (NPWT) on bone regeneration in rat calvarial defects, results showed that NPWT significantly promoted bone regeneration and osteogenic activity. PMC9466622
Rats Optic nerve crush model Intravitreal injection 7 days continuously To evaluate the protective effect of SBI-0206965 on acute axonal degeneration, results showed that 50 μM SBI significantly increased the axonal integrity ratio. PMC7493890
Mice CT26 subcutaneous tumor model Intraperitoneal injection 50 μM Single injection, observation for 6 hours To evaluate the anti-tumor efficacy of SBI-0206965 in the CT26 subcutaneous tumor model, it was found to significantly increase the number of functional T cells (CD4+ granzyme B+ and CD8+ granzyme B+ T cells) and optimize tumor vascular structure. PMC11667230
BALB/c nude mice A498 xenograft model Intraperitoneal injection 3.0 mg/kg Once daily for 3 days SBI-0206965 significantly inhibited the growth of A498 xenograft tumors and induced tumor cell apoptosis. PMC6116477
SKH-1 hairless mice NM-induced dermal toxicity model intraperitoneal injection 20 mg/kg Twice per week, until tumor volume reached 2000 mm³ Capsazepine treatment significantly inhibited NM-induced TRPV1 signaling pathway activation, thereby attenuating NM-induced autophagy and skin injury. PMC7829253

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.04mL

0.41mL

0.20mL

10.22mL

2.04mL

1.02mL

20.44mL

4.09mL

2.04mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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