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Chemical Structure| 1422253-37-9 Chemical Structure| 1422253-37-9

Structure of C-82
CAS No.: 1422253-37-9

Chemical Structure| 1422253-37-9

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C-82 is a selective β-catenin/CBP inhibitor with high affinity for β-catenin/CBP, with an IC50 value of 0.8 μM. C-82 exhibits antitumor activity and can be used in research on colorectal cancer and other β-catenin-related cancers.

4.5 *For Research Use Only! Not for Human Use. We Do Not Sell to Patients.

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Product Citations

Product Citations

Pan, Mengya ; Jiao, Changqing ; Sun, Menghua ; Jin, Duo ; Wang, Yin ; Wu, Haoxuan , et al.

Abstract: Background: Due to compensatory survival signalling and overexpression of anti-apoptotic Bcl-2 family proteins, the majority of AML patients developed acquired resistance of venetoclax (VEN) to combination therapy of VEN with low-dose cytarabine (LDAC) or hypomethylating agents (HMAs). Dysregulation of the Wnt/β-catenin signalling pathway is intently associated with leukemia development and chemotherapy resistance. However, there is currently no Wnt/β-catenin inhibitor approved for clinical use and it is not clear whether targeting the Wnt/β-catenin pathway enhances the anti-leukemic activity of VEN. Methods: Analysis of the AML patient’s data in the BeatAML and GEO databases. Establishing the MOLM13 venetoclax-resistant cell line (MOLM13-R cells) based on the MOLM13 parental cell line. CCK-8, Annexin-V/PI and Western blotting were performed to assess the effects of the combination of Wnt/β-catenin inhibitor C-82 and VEN in AML cell lines. The potential mechanisms of synergistic effects of the two-drug combination were explored by Western blotting and ubiquitination immunoprecipitation. Results: We displayed that the expression of β-catenin abnormally upregulated in AML patients and MOLM13-R cells. Knockdown of β-catenin could increase cell apoptosis in MOLM13-R cells. Combined treatment of C-82 with VEN synergistically inhibited AML cell growth and increased apoptosis. Mechanistically, C-82 disrupted the stability of Mcl-1 protein, and Mcl-1 downregulation was associated with different phosphorylation sites of Mcl-1 and proteasomal degradation. The combination of C-82 and VEN synergistically induced concurrent mitochondrial-associated apoptosis and gasdermin E (GSDME)-dependent pyroptosis. Conclusion: Our findings propose an effective treatment strategy for AML patients through the combination of C-82 and VEN, positioning this regimen as a promising therapeutic option.

Keywords: Acute myeloid leukemia ; Venetoclax ; Drug resistance ; Wnt/β-catenin ; Mcl-1

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Product Details of C-82

CAS No. :1422253-37-9
Formula : C33H34N6O4
M.W : 578.66
SMILES Code : O=C(N([C@]([C@H](C)N1CC2=C3N=CC=CC3=CC=C2)([H])N4[C@@H](CC5=CC=C(O)C=C5)C1=O)N(C)CC4=O)NCC6=CC=CC=C6
English Name :(6S,9S,9aS)-N-Benzyl-6-(4-hydroxybenzyl)-2,9-dimethyl-4,7-dioxo-8-(quinolin-8-ylmethyl)hexahydro-2H-pyrazino[2,1-c][1,2,4]triazine-1(6H)-carboxamide
MDL No. :MFCD32664545
InChI Key :KLGHKOORFHZFGO-AZXNYEMZSA-N
Pubchem ID :73602848

Safety of C-82

Related Pathways of C-82

epigenetics

Isoform Comparison

Biological Activity

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT02349009 Systemic Scleroderma Phase 1 Phase 2 Completed - United States, Illinois ... More >> Chicago, Illinois, United States United States, Massachusetts Boston, Massachusetts, United States United States, New York New York, New York, United States Less <<
NCT02432027 Psoriasis Phase 1 Phase 2 Completed - Germany ... More >> Schwerin, Germany Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.73mL

0.35mL

0.17mL

8.64mL

1.73mL

0.86mL

17.28mL

3.46mL

1.73mL

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