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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.

4.5 *For Research Use Only !

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Product Citations

Product Citations

Zhang, Chenliang ; Huang, Chen ; Xia, Hongwei ; Xu, Huanji ; Tang, Qiulin ; Bi, Feng

Abstract: Aggresome formation is a protective cellular response to counteract proteasome dysfunction by sequestering misfolded proteins and reducing proteotoxic stress. Autophagic degradation of the protein aggregates is considered to be a key compensating mechanism for balancing proteostasis. However, the precise role of autophagy in proteasome inhibition-induced aggresome biogenesis remains unclear. Herein, we demonstrate that in the early stage of proteasome inhibition, the maturation of the autophagosome is suppressed, which facilitates aggresome formation of misfolded proteins. Proteasome inhibition-induced phosphorylation of SQSTM1 T269/S272 inhibits its autophagic receptor activity and promotes aggresome formation of misfolded proteins. Inhibiting SQSTM1 T269/S272 phosphorylation using Doramapimod aggravates proteasome inhibitor-mediated cell damage and tumor suppression. Taken together, our data reveal a negative effect of autophagy on aggresome biogenesis and cell damage upon proteasome inhibition. Our study suggests a novel therapeutic intervention for proteasome inhibitor-mediated tumor treatment.

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Alternative Products

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

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

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