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Chemical Structure| 1258392-53-8 Chemical Structure| 1258392-53-8

Structure of AZD5582
CAS No.: 1258392-53-8

Chemical Structure| 1258392-53-8

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AZD5582 is a class of dimeric Smac mimetics as potent IAP antagonist and binds potently to the BIR3 domains of cIAP1, cIAP2, and XIAP (IC50 = 15, 21, and 15 nM, respectively).

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Product Details of AZD5582

CAS No. :1258392-53-8
Formula : C58H78N8O8
M.W : 1015.28
SMILES Code : CN[C@@H](C)C(N[C@H](C(N1[C@H](C(N[C@H]2C3=CC=CC=C3C[C@H]2OCC#CC#CCO[C@H]4[C@@H](NC([C@@H]5CCCN5C([C@@H](NC([C@H](C)NC)=O)C6CCCCC6)=O)=O)C(C=CC=C7)=C7C4)=O)CCC1)=O)C8CCCCC8)=O
MDL No. :MFCD28411397
InChI Key :WLMCRYCCYXHPQF-ZVMUOSSASA-N
Pubchem ID :49847690

Safety of AZD5582

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

Isoform Comparison

Biological Activity

Target
  • cIAP

    cIAP1, IC50:15 nM

    cIAP2, IC50:21 nM

  • XIAP

    XIAP, IC50:15 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
Jurkat cells 5 nM 16 hours To investigate the role of AZD5582 in HIV-1 latency reversal, results showed that AZD5582 induces HIV-1 gene expression by activating the ncNF-κB pathway PMC9705157
breast cancer cell lines 10 nM 2 and 8 hours evaluate the synergism between AZD5582 and TRAIL, observed highly synergistic activity in ~30% of cell lines PMC4632282
Total CD4+ T cells 100 nM 24 hours To evaluate the effect of AZD5582 on the ncNF-κB pathway, results showed that AZD5582 degrades cIAP1 and activates p100/p52. PMC7111210
Jurkat cells 1-10 nM 24 hours To evaluate the effect of AZD5582 on HIV latency reversal, results showed that AZD5582 significantly reversed HIV latency. PMC8728431
U1 cells 500 nM 24 hours To evaluate the effect of AZD5582 on HIV latency reversal in U1 cells, results showed that high concentration AZD5582 reversed HIV latency. PMC8728431
A66 cells 33 ng/ml 4 hours To assess viral gene expression in SIVmac239-infected cells PMC10579098
Jurkat cells 10 pM to 1 μM 48 hours To evaluate the induction of HIV transcription by AZD5582, results showed that AZD5582 effectively induces HIV transcription. PMC7111210
Primary CD4+ T cells 100 nM 48 hours To evaluate the effect of AZD5582 on HIV latency reversal in primary CD4+ T cells, results showed that AZD5582 reversed HIV latency. PMC8728431
H1975 human NSCLC cell line 20 nM 48 hours AZD5582 alone slightly inhibited cell viability, but it could cooperate with IFNγ to profoundly induce cell death PMC6001173
HCC827 human NSCLC cell line 20 nM 48 hours AZD5582 plus IFNγ significantly induced cell death, and apoptosis was detected by Annexin V PMC6001173
H1437 human NSCLC cell line 20 nM 60 hours AZD5582 plus IFNγ significantly induced cell death PMC6001173
A549 human NSCLC cell line 20 nM 72 hours AZD5582 alone had a minor effect on cell viability, but it could cooperate with IFNγ to induce cell death PMC6001173
Calu-3 human NSCLC cell line 20 nM 72 hours AZD5582 alone or plus IFNγ did not significantly affect cell viability PMC6001173
H441 human NSCLC cell line 20 nM 72 hours AZD5582 alone or plus IFNγ did not significantly affect cell viability PMC6001173
Primary normal human alveolar epithelial cells 20 nM 72 hours AZD5582 alone or plus IFNγ did not significantly affect cell viability PMC6001173
Hepa1-6 cells 25 µM AZD5582 synergistically with heat treatment significantly decreased the viability of Hepa1-6 cells, inhibited cell migration and proliferation, and induced apoptosis. PMC11798986
Huh7 cells 25 µM AZD5582 synergistically with heat treatment significantly decreased the viability of Huh7 cells, inhibited cell migration and proliferation, and induced apoptosis. PMC11798986
PANC-1 1.21 μM To evaluate the inhibitory effect of AZD5582 on the proliferation of pancreatic cancer cells PMC10921007
CFPAC-1 74.03 nM To evaluate the inhibitory effect of AZD5582 on the proliferation of pancreatic cancer cells PMC10921007
Total CD4+ T cells 100 nM 48 h Analyze the targeting effect of AZD5582 on the ncNF-κB pathway, results showed AZD5582 effectively degraded cIAP1 and activated p100/p52 PMC7111210
Jurkat cells 10 pM to 1 μM 48 h Evaluate the induction of HIV transcription by AZD5582, results showed AZD5582 effectively induced HIV transcription PMC7111210

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
BLT humanized mice HIV-1 infection model Intraperitoneal injection 3 mg/kg Single dose To evaluate the effect of AZD5582 on HIV latency reversal, results showed that AZD5582 induces HIV-RNA expression, particularly in multiple tissues. PMC7111210
Rhesus macaques SIVmac239 infection model Intravenous injection 0.1 mg/kg Weekly for 5 weeks To evaluate the latency reversal effect of AZD5582 in ART-suppressed SIV-infected rhesus macaques PMC10579098
C57BL/6J mice and NTG mice Hepatocellular carcinoma xenograft model Intraperitoneal injection 0.3 mg/kg Once every 2 days for 12 days AZD5582 in combination with IMWA significantly inhibited the progression of hepatocellular carcinoma, induced apoptosis, and inhibited cell proliferation, while increasing the infiltration of CD8+ T cells and decreasing the infiltration of Foxp3+ regulatory T cells in the tumor microenvironment. PMC11798986
Mice PDX model Intravenous injection 3 mg/kg Once a week for 3 weeks To evaluate the inhibitory effect of AZD5582 on pancreatic cancer growth in the PDX model PMC10921007

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

0.98mL

0.20mL

0.10mL

4.92mL

0.98mL

0.49mL

9.85mL

1.97mL

0.98mL

References

 

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