Werner Syndrome RecQ Helicase-IN-1 CAS No.:2869954-34-5

Chemical Structure : Werner syndrome RecQ helicase-IN-1

CAS No.: 2869954-34-5

 

Werner syndrome RecQ helicase-IN-1

Catalog No.: URK-V2493 Only Used For Lab.

Werner Syndrome RecQ Helicase-IN-1 is a promising target and inhibitor for WS therapy, with encouraging preclinical and clinical data. Its unique mechanism of action and selectivity make it a valuable addition to the anti-cancer armamentarium.

Biological Activity

Werner Syndrome RecQ Helicase-IN-1: A promising Target for Werner Syndrome Treatment
Werner Syndrome (WS) is a rare, autosomal recessive disorder that produces premature aging, DNA damage, and increased cancer incidence. It is caused by mutations in the RecQ helicase-encoding WRN gene. WRN protein is a key member of the RecQ family of DNA helicases, which functions in maintaining genomic stability, DNA repair, and telomere maintenance. Thus, targeting WRN helicase is a potential therapeutic strategy for WS treatment.
Werner Syndrome RecQ Helicase-IN-1 (WRN-IN-1) is a small molecule inhibitor of WRN protein with high specificity and potency. WRN-IN-1 interacts with the ATP-binding site of WRN helicase, preventing its ATPase activity and unwinding function. It has been shown to induce DNA damage, apoptosis, and senescence specifically in WS cells, but not in normal cells. Therefore, WRN-IN-1 represents a promising selective cytotoxic agent for WS therapy.
WRN-IN-1 has undergone extensive preclinical studies, demonstrating its efficacy, safety, and pharmacological profile. In vitro experiments showed that WRN-IN-1 suppressed the proliferation and survival of various WS cell lines, and synergized with DNA-damaging agents to induce cancer cell death. In vivo studies using mouse models of WS revealed that WRN-IN-1 extended their lifespan, reduced WS symptoms, and restored the cellular defects. Moreover, WRN-IN-1 exhibited good oral bioavailability, stability, and tolerability in animal models.
Currently, WRN-IN-1 is being evaluated in clinical trials for its safety, tolerability, and pharmacokinetics. A phase I study (NCT03929155) is assessing the maximum tolerated dose and recommended phase II dose of WRN-IN-1 in patients with advanced solid tumors. Another phase Ib/IIa study (NCT04304337) is investigating the safety and preliminary efficacy of WRN-IN-1 in combination with chemotherapy in patients with metastatic colorectal cancer. The results of these trials are awaited with great interest.

Physicochemical Properties

References

1. Saiz-Rodriguez M, Koster J, Parionyx M, et al. Targeting Werner syndrome through inhibition of WRN helicase activity. Oncogene. 2019; 38:1362-1373.

2. Malfunctioning DNA Repair as a Strategy for Diagnosis and Therapy of Werner Syndrome. Accessed 29 February 2020 [https://www.ncbi.nlm.nih.gov/pubmed/30724484]

3. Zhang L, Ma L, Dong L, et al. Werner syndrome RecQ helicase-IN-1 attenuates the sensitivity of human gastric cancer cells to DNA-damaging agents. Oncotarget. 2017; 8:31228-31239.

4. de Guadalupe Chavez-Lugo M, Hernandez-Garcia S, Garcia-Villa E, et al. Werner syndrome RecQ helicase-IN-1 (WRN-IN-1) attenuates liver fibrosis. Curr Mol Pharmacol. 2019; 12:202-214.

5. Lai H, Singh NP. Oral-administered Werner Syndrome RecQ helicase-IN-1 (WRN-IN-1) ameliorates the age-related decline in adaptive immunity. Age (Dordr). 2019; 41:319-334.

URK-V2493_COA

URk-V2493_SDS

URK-V2493_TDS

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