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Chemical Structure| 2869954-34-5 Chemical Structure| 2869954-34-5

Structure of HRO761
CAS No.: 2869954-34-5

Chemical Structure| 2869954-34-5

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HRO761 is a potent, selective, heterogeneous WRN inhibitor that binds to the interfaces of the D1 and D2 helicase domains, locking WRN in inactive conformation. HRO761 has the potential to be used in the study of multiple cancers (such as MSI-H colorectal cancer, other solid tumors, etc.).

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Product Details of HRO761

CAS No. :2869954-34-5
Formula : C31H31ClF3N9O5
M.W : 702.08
SMILES Code : O=C(NC1=CC=C(C(F)(F)F)C=C1Cl)CN(C(CC)=C2N3CCN(C(C4=NC=NC(C)=C4O)=O)CC3)C5=NC(C6=CCOCC6)=NN5C2=O
MDL No. :N/A

Safety of HRO761

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319
Precautionary Statements:P501-P270-P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313-P301+P312+P330

Related Pathways of HRO761

DNA

Isoform Comparison

Biological Activity

Description
Werner syndrome RecQ helicase-IN-1 (example 42) acts as a potent inhibitor of Werner syndrome RecQ DNA helicase enzyme (WRN), making it valuable for cancer research [1].

In Vitro:

Cell Line
Concentration Treated Time Description References
SW48 cells 40 nM (GI50) 4 days To assess the growth inhibitory effect of HRO761 on SW48 cells. Results showed that HRO761 had a GI50 of 40 nM in SW48 cells. PMID: 38658754
ADP-Glo kinase assay 30.8 nM (IC50) To evaluate the enzyme inhibitory and antiproliferative activity of HRO761 in HCT116 cells. Results showed HRO761 exhibited potent WRN helicase inhibitory activity and antiproliferative activity. PMID: 39561494
Fluorometric helicase assay 29.8 nM (IC50) To evaluate the enzyme inhibitory and antiproliferative activity of HRO761 in HCT116 cells. Results showed HRO761 exhibited potent WRN helicase inhibitory activity and antiproliferative activity. PMID: 39561494
HCT116 or SW48 cells 78.5 nM (GI50) To evaluate the enzyme inhibitory and antiproliferative activity of HRO761 in HCT116 cells. Results showed HRO761 exhibited potent WRN helicase inhibitory activity and antiproliferative activity. PMID: 39561494
HCT116 or SW48 cells 28.4 nM (GI50) To evaluate the enzyme inhibitory and antiproliferative activity of HRO761 in HCT116 cells. Results showed HRO761 exhibited potent WRN helicase inhibitory activity and antiproliferative activity. PMID: 39561494

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Athymic nude (Crl:NU(NCr)-Foxn1nu) mice SW48-cell-derived xenografts Oral 20 mg/kg Once daily for up to 60 days To assess the anti-tumour effect of HRO761 in SW48-cell-derived xenografts. Results showed that HRO761 led to tumour stasis at 20 mg per kg and significant tumour regressions at higher doses. PMID: 38658754
Rats Sprague–Dawley Rats Intravenous administration 1 mg/kg HR0761 was quickly eliminated from the plasma with the elimination halflifeof 1.9h. PMID: 39995302
Rats Sprague–Dawley Rats Oral 5, 10, and 20 mg/kg HRO761 was quickly absorbed into plasma and reach the pealconcentration (C) of 2598.1-9379.2ng/mL at 1.0-4.0 h. PMID: 39995302

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.42mL

0.28mL

0.14mL

7.12mL

1.42mL

0.71mL

14.24mL

2.85mL

1.42mL

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

References

 

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