Date published: 2025-11-24

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HELB Inhibitors

HELB inhibitors as a chemical class refer to a group of compounds that indirectly affect the function or activity of the HELB protein through modulation of various cellular signaling pathways. These chemicals do not inhibit HELB by binding directly to the protein or its active sites. Instead, they exert their effects on cellular processes and signaling pathways that are crucial for the proper functioning of HELB or on the biological outcomes that HELB influences.

The chemical inhibitors listed target key proteins involved in DNA damage response and repair, such as ATR, ATM, DNA-PK, and Chk1. By inhibiting these kinases, the chemicals disrupt the signaling pathways that orchestrate the cellular response to DNA damage and replication stress, where HELB plays a critical role. For instance, ATR Inhibitor VE-821 and ETP-46464 specifically inhibit ATR kinase, attenuating the cellular response to replication stress, a condition that necessitates HELB activity. Similarly, ATM kinase, targeted by KU-55933 and CGK733, is critical for the response to DNA double-strand breaks, a process where HELB's helicase activity is involved. DNA-PK inhibitors like NU7441 and NU7026 are known to affect DNA repair pathways, particularly non-homologous end joining, which can implicate HELB function. The inhibition of Chk1 by compounds such as PF-477736 and AZD7762 disrupts cell cycle checkpoints, potentially influencing HELB's roles during DNA replication and repair.

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