instability

Elimusertib (BAY-1895344) is a potent, highly selective, and orally available ATR inhibitor with an IC50 of 7 nM, demonstrating significant anti-tumor efficacy as a monotherapy and strong combination potential with targeted alpha therapy Radium-223 dichloride.

Shield-1 is a specific, high-affinity, and cell-permeable ligand for FK506-binding protein 12 (FKBP) and reverses instability by binding to mutant FKBP (mtFKBP), allowing conditional expression of mtFKBP fusion proteins.

Niraparib, also know as MK-4827, is an inhibitor of poly (ADP-ribose) polymerase (PARP) with potential antineoplastic activity. MK4827 inhibits PARP activity, enhancing the accumulation of DNA strand breaks and promoting genomic instability and apoptosis. The PARP family of proteins detect and repair single strand DNA breaks by the base-excision repair (BER) pathway.

Terodiline is a seconal amine with anticholinergic and calcium antagonistic properties that blocks the hERG current (IC50: 375 nM).Terodiline is cardiotoxic and has been used in the study of disorders caused by urethral muscle instability.

GSK4418959 (IDE275) is a non-covalent, reversible, selective, and orally active inhibitor of the Werner syndrome helicase (WRN helicase). GSK4418959 inhibits both ATPase and DNA unwinding activities of WRN helicase in an ATP-competitive manner. GSK4418959 is a valuable chemical tool for the study of microsatellite instability-high (MSI-H) cancers, where WRN helicase plays an essential role in maintaining genomic stability.

2-CEES is a mustard gas analogue that only forms DNA monoadducts. It induces centromere amplification in both human and mouse cells and can lead to chromosome instability.

WRN-IN-19 (Compound (S)-27) is a covalent WRN helicase inhibitor, with a pIC50 of 5.4 at 0 hours and 7.5 at 4 hours in a DNA-unwinding endpoint assay. It demonstrates synthetic lethality against MSI-H (high microsatellite instability) cancer cells.

MU262 is a structurally novel polycyclic heterocyclic small-molecule compound and a MUS81 inhibitor with an IC₅₀ value of 0.87 μM, which directly inhibits MUS81 catalytic activity through non-interfering DNA binding, inducing genomic instability in tumor cells and specifically inhibiting the HR/BIR repair pathways. MU262 can serve as a chemical biology tool for studying MUS81 function and as a lead compound for developing anticancer therapies that exploit DNA repair defects in cancer cells.

Enpp-1-IN-29 (Compound 1) is a highly selective inhibitor of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) with an IC50 of 0.05 nM. This compound shows potential for research into cancers with overexpressed ENPP1, such as breast cancer, head and neck cancer, and metastatic chromosomal instability tumors, as well as immunological disorders like autoimmune diseases and tumor immune evasion.

KIF18A-IN-18 (Compound I) serves as an inhibitor of KIF18A and is applicable in studies of tumors characterized by chromosomal instability.

GSTO1-IN-6 is an allosteric covalent inhibitor of GSTO1 with an IC50 of 457 nM. It significantly reduces lipopolysaccharide (LPS)-induced secretion of IL-1β with an IC50 of 1.9 μM and IL-18 with an IC50 of 10 μM in human monocyte-derived macrophages. GSTO1-IN-6 covalently binds to GSTO1-Cys32, inducing conformational changes and protein instability. This compound is applicable in the study of inflammatory diseases.

DL78 is a potent antimitotic agent that induces mitotic arrest, mitotic catastrophe, and apoptosis in cancer cells by disrupting the interaction between Myc and α-tubulin. It exhibits broad anticancer activity, particularly targeting cancer cells characterized by chromosomal instability and MYC overexpression. In the OV81.2 xenograft model, DL78 significantly reduces tumor burden. DL78 can be employed in ovarian cancer research.

MS1-96 is an orally active PD-L1 (programmed death-ligand 1) degrader. It effectively reduces PD-L1 protein expression levels in various colorectal cancer (CRC) cell lines. The compound loses its ability to induce PD-L1 degradation upon HIP1R knockdown. MS1-96 binds directly to PD-L1 (KD= 2.58 μM) and enhances the interaction between HIP1R and PD-L1, altering PD-L1's intracellular transport in clathrin-coated vesicles. Additionally, MS1-96 induces abnormal N-glycosylation of PD-L1, leading to protein instability and accelerated lysosome-mediated degradation. MS1-96 is applicable for colorectal cancer research.

WRN-IN-24 is an orally active allosteric covalent inhibitor of the Werner syndrome RecQ DNA helicase (WRN), with an IC50 of 201 nM. It binds to a novel allosteric cavity, forming an additional hydrogen bond with K894, thereby functionally inhibiting WRN activity. WRN-IN-24 suppresses the proliferation of colorectal cancer cells and demonstrates dose-dependent antitumor activity in xenograft mouse models. This compound is applicable in research on cancers with high microsatellite instability, including colorectal cancer.

WRN-IN-25 is an allosteric Werner syndrome helicase (WRN) inhibitor with an IC50 of 15 nM and a Kd of 54 nM. It induces DNA damage, reduces cell viability, and exhibits a synthetic lethal effect in WRN-dependent cancer cells with high microsatellite instability. WRN-IN-25 is applicable for research related to microsatellite unstable cancers.

WRN-IN-23 is an inhibitor of the Werner syndrome helicase (WRN). It suppresses the ATP-dependent helicase domain activity of WRN. WRN-IN-23 is utilized in research focusing on cancers characterized by microsatellite instability (MSI) and/or deficiencies in the DNA mismatch repair system (dMMR).

Multi-target kinase-IN-9 is a multi-target enzyme inhibitor with antiproliferative and antiangiogenic activity, showing significant selectivity for liver cancer cells. By extensively binding to active sites or ATP-binding regions of several key enzymes, such as DNA polymerase β and pyruvate kinase M2 (PKM2), it disrupts DNA repair and replication, glycolysis, chromatin dynamics, and transcriptional programs, blocking cancer stem cell self-renewal. This compound induces genomic instability, lysosomal dysfunction, and autophagic flux interruption, leading to tumor cell death. It effectively inhibits tumor proliferation, invasion, metastasis, and angiogenesis, significantly reducing tumor volume in xenograft models. Multi-target kinase-IN-9 is applicable in liver cancer research.

MKI-3 is a selective inhibitor of microtubule-associated serine/threonine-like kinase (MASTL), with an IC50 of 5.72 nM and a Kd of 1.89 nM. It disrupts the MASTL-ENSA-Aurora A signaling axis. Additionally, MKI-3 induces chromosomal instability, mitotic catastrophe, and apoptosis in cancer cells, and can be utilized in research related to triple-negative breast cancer.

DHX9-IN-21 (Compound 635) is a DHX9 inhibitor with an IC50 of 2 nM; it has an EC50 of 19.1 nM at the cellular level. This compound exhibits antiproliferative activity against LS411N (CRC-MSI-H) with an IC50 of 79.2 nM. DHX9-IN-21 is applicable in research on microsatellite instability in colorectal cancer.

Tolterodine ((R)-(+)-Tolterodine) is a novel and selective muscarinic-type receptor (mAChR) antagonist used in the treatment of detrusor instability and overactive bladder syndrome.

ML381 (VU0488130) is a highly selective, central nervous system-penetrant mAChR M5 orthogonal antagonist with nanomolar potency that exhibits instability in rat plasma, limiting its in vivo utility while establishing its primary value as a molecular probe for in vitro pharmacological characterization and electrophysiological studies of M5 receptor function.

Pamiparib is a highly potent and selective PARP inhibitor. BGB-290 selectively binds to PARP and prevents PARP-mediated repair of single-strand DNA breaks via the base-excision repair (BER) pathway. This enhances the accumulation of DNA strand breaks, pro

Niraparib hydrochloride (MK-4827 hydrochloride) is an inhibitor of poly (ADP-ribose) polymerase (PARP) with potential antineoplastic activity. By inhibiting PARP activity, niraparib hydrochloride increases DNA strand breaks, leading to genomic instability and apoptosis. The PARP family of proteins detects and repairs single-strand DNA breaks via the base-excision repair (BER) pathway.

5-Hydroxymethyl-2'-deoxycytidine is an oxidized derivative of 5-methyl-2'-deoxycytidine (5-mdC) in DNA, causing DNA damage reactions, chromosomal aberrations, replication fork damage, and loss of cell viability.5-Hydroxymethyl-2'-deoxycytidine is an oxidized derivative of 5-methyl-2'-deoxycytidine in DNA. Hydroxymethyl-2'-deoxycytidine replication fork instability is associated with the presence of poly(ADP-ribose) polymerase 1 (PARP1) on chromatin.