Helicases Inhibitor

PolQi2 is a PolΘ inhibitor that targets and inhibits alt-EJ (alternative end-joining) repair by inhibiting the helicase domain at the N-terminus of PolΘ. PolQi2 enhances the precision and integration efficiency of gene editing at different loci and in various cell lines. Furthermore, the combined use of PolQi2 with DNA-PK inhibitors reduces the off-target effects of Cas9. PolQi2 can be used in gene editing research.

HRO761 (Werner syndrome RecQ helicase-IN-1) (example 42) is a potent Werner syndrome RecQ DNA helicase enzyme (WRN) inhibitor and can be used in cancer research.

RK-33 is an RNA helicase inhibitor against DDX3, and inhibits its helicase activity.

VVD-214 is a synthetic lethal allosteric inhibitor of WRN helicase with an IC₅₀ of 0.1316 µM. VVD-214 covalently binds to cysteine 727 of WRN and inhibits ATP hydrolysis and helicase activity. VVD-214 is potent in causing double-stranded DNA breaks, nuclear swelling, and cell death in high microsatellite instability (MSI) cancers.

DNA2 inhibitor C5 is a potent, competitive, and specific DNA2 nuclease inhibitor with an IC₅₀ of 20 μM. DNA2 inhibitor C5 inhibits the nuclease, DNA-dependent ATPase, helicase, and DNA-binding activities of DNA2. DNA2 inhibitor C5 can be used in breast cancer and colorectal cancer research.

Avenanthramide A is an orally active phytoalexin that targets the RNA helicase DDX3 with a K_D of 8.8 μM. Avenanthramide A induces mitochondrial swelling and increased ROS production, and triggers apoptosis in CRC cells. Avenanthramide A inhibits smooth muscle cell proliferation and enhances nitric oxide production. Avenanthramide A can be used in research on colorectal cancer and atherosclerosis.

SY-589 is an orally active DNA polymerase Polθ helicase domain inhibitor (IC₅₀=2.29 nM) and DNA damage inducer. SY-589 inhibits the ATPase activity of the Polθ helicase domain and blocks the Polθ-mediated microhomology-mediated end joining (MMEJ) DNA repair pathway (IC₅₀=0.85 nM). SY-589 also induces the accumulation of DNA double-strand breaks by increasing γ-H2AX levels. SY-589 exerts antiproliferative effects on BRCA2-deficient cells and is used in the research of HR-deficient tumors.

DHX8-IN-1 is a DHX8 inhibitor with an IC₅₀ of 40 nM in ATPase activity assays. DHX8-IN-1 can be used in research on DHX8-related diseases such as Dupuytren's contracture and HIV-1 infection.

ML216 (CID-49852229) is a potent, selective and cell permeable inhibitor of the DNA unwinding activity of BLM helicase with IC₅₀s of 2.98 μM and 0.97 μM for BLM^full-length and BLM^636-1298, respectively. ML216 inhibits ssDNA-dependent ATPase activity of BLM with a K_i of 1.76 μM. Antitumor avtivity.

TK216 is an orally active and potent E26 transformation specific (ETS) inhibitor. TK216 directly binds EWS-FLI1 and inhibits EWS-FLI1 protein interactions. TK216 blocks the binding between EWS-FLI1 and RNA helicase A. TK216 has anticancer activity.

NSC 617145 is a selective werner syndrome helicase (WRN) helicase inhibitor with an IC₅₀ value of 230 nM. NSC 617145 inhibits WRN ATPase, and induces double-strand breaks (DSB) and chromosomal abnormalities. NSC 617145 shows selective for WRN over BLM, FANCJ, ChlR1, RecQ, and UvrD helicases.

YK-4-279 blocks RNA Helicase A (RHA) binding with EWS-FLI1 (oncogenic protein). YK-4-279 induces apoptosis and shows anti-proliferation activities towards various cancer cells. YK-4-279 has a chiral center and it can be separated into two enantiomers. YK-4-279 can be used for the research of cancer.

DHX9-IN-1 is an inhibitor of ATP-dependent RNA helicase A (DHX9). Its EC₅₀ value is 1.41 μM. DHX9-IN-1 has anti-tumor activity and can be used in colorectal cancer research.

GSK4418959 (IDE275) is a selective, reversible and orally active WRN helicase inhibitor. GSK4418959 shows >10,000-fold selectivity over other helicases. GSK4418959 inhibits ATPase and DNA unwinding functions in an ATP-competitive manner. GSK4418959 can be used for the study of microsatellite instability-high (MSI-H) cancer, such as colorectal cancer (CRC) and endometrial cancer (EC).

KY386 is a DHX33 helicase inhibitor with an IC₅₀ of 0.019 μM. KY386 inhibits the cell viability of various cancer cells. KY386 induces ferroptosis in cancer cells, and induces apoptosis in some cancer cell lines. KY386 increases the intracellular levels of ROS, LPO and Fe²⁺, and decreases the level of GSH in cancer cells. KY386 inhibits the growth of gastric cancer and colon cancer xenografts in nude mice. KY386 is applicable to the related research on liver cancer, lung cancer, pancreatic cancer, colorectal cancer, gastric cancer, breast cancer, leukemia, renal cancer, prostate cancer, esophageal cancer, cervical cancer, brain cancer (glioblastoma) and melanoma.

AB25583 is a Polθ helicase (Polθ-hel) small molecule inhibitor, with an IC₅₀ value of 6 nM. AB25583 selectively kills BRCA1/2 deficient cells and works in synergy with Olaparib (HY-10162) in cancer cells carrying pathogenic BRCA1/2 mutations. AB25583 can be used for tumor research.

Supinoxin (RX-5902) is an orally active inhibitor of phosphorylated-p68 RNA helicase (P-p68) and a potent first-in-class anti-cancer agent. Supinoxin interacts with Y593 phosphorylated-p68 and attenuates the nuclear shuttling of β-catenin. Supinoxin induces cell apoptosis and inhibits growth of TNBC cancer cell lines with IC₅₀s ranging from 10 nM to 20 nM.

DHX9-IN-3 (Compound 621) is an inhibitor of ATP-dependent RNA helicase A (DHX9). DHX9-IN-3 has an IC₅₀ of 8.7 nM for anti-proliferation in LS411N cells. DHX9-IN-3 can be used in the study of cancer.

CHD1Li 6.11 is a potent and orally active Chromodomain Helicase DNA Binding Protein 1 Like (CHD1L) (oncogenic gene) inhibitor (IC₅₀ = 3.3 µM for cat-CHD1L recombinant protein). CHD1Li 6.11 can inhibit EMT, induce mesenchymal-epithelial transition (reverse EMT) and promote apoptosis in tumor organoid models. CHD1Li 6.11 can be used for the research of cancer, such as colorectal cancer.

RECQL5-IN-1 (Compound 4a) acts as an orally effective RECQL5 inhibitor (targeting both enzymatic and nonenzymatic domain). RECQL5-IN-1 is a potent inhibitor of RECQL5 helicase activity (IC₅₀=46.3 nM), stabilizes the interaction between RECQL5-RAD51 proteins, causes RAD51 aggregation and homologous recombination repair (HRR) inhibition, thereby exhibiting selective cytotoxicity in RECQL5-expressing cancer cells.