dna damage response

AGI-24512 is a potent inhibitor of methionine adenylyltransferase 2α (MAT2A) (IC50: 8 nM).AGI-24512 shows antiproliferative activity in MTAP-deficient cancer cells.AGI-24512 inhibits MAT2A, which causes DNA damage in MTAP, and is often used in conjunction with anticancer compounds in cancer research.

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.

SSK1 is a compound that selectively kills senescent cells and is a precursor for β-galactosidase, which can reduce the inflammatory response of the body. SSK1 can activate the phosphorylation of p38 MAPK and MKK3/MKK6 in senescent cells, and promote mitochondrial DNA damage in senescent cells.

L-Glutamic acid monosodium salt monohydrate (MSG monohydrate) is an important food additive with gastrointestinal protective effects. It plays a critical role in nutrient metabolism, energy demand, immune response, oxidative stress, signal transduction, and synaptic transmission. L-Glutamic acid monosodium salt monohydrate can induce oxidative stress, DNA damage, and apoptosis in mouse liver and brain tissues. It can protect against gastrointestinal damage caused by NSAIDs and Helicobacter pylori through multiple mechanisms.

BLM-IN-1 is a potent inhibitor of Bloom syndrome protein (BLM) with a KD of 1.81 μM and IC50 of 0.95 μM. It induces DNA damage response, apoptosis, and proliferation arrest in cancer cells.

PROTAC PARP1 degrader is a targeted protein degrader of PARP1 developed using PROTAC technology, and at 10 μM for 24 hours inhibits the proliferation of the MDA-MB-231 breast cancer cell line with an IC50 of 6.12 μM, providing a powerful research tool for studying DNA damage response, PARP1 biology, and degradation-based cancer therapeutics.

BMH-21, a small molecule DNA intercalator, binds ribosomal DNA and inhibits RNA polymerase I (Pol I) transcription and not affects phosphorylation of H2AX.

KL-50, a selective toxin, effectively targets tumors deficient in the DNA repair protein O6-methylguanine-DNA-methyltransferase (MGMT), which corrects O6-alkylguanine lesions. This compound induces both DNA damage response pathways and cell cycle arrest in MGMT-deficient cells, regardless of mismatch repair (MMR) status. KL-50 shows promise in the study of brain tumors lacking MGMT.

Adenosine 5′-diphosphoribose (ADP ribose), formed from adenosine monophosphate (AMP) and ribose via phosphoribosyl pyrophosphate, is a multifunctional modifier of proteins and nucleic acids, playing crucial roles in diverse cellular processes.

CDK12/13-IN-3 (Compound 12b) is an orally active CDK inhibitor targeting CDK12 and CDK13, with IC50 values of 107.4 nM and 79.4 nM, respectively. This compound inhibits the phosphorylation of Ser2 on the CTD of RNA polymerase II, induces DNA damage, and downregulates the gene expression involved in the DNA damage response (DDR). CDK12/13-IN-3 exhibits antiproliferative effects against various cancer cells with nanomolar IC50 values. In mouse models, it demonstrates antitumor activity, favorable pharmacokinetic properties, and an oral bioavailability of 53.6%.

CHK1-IN-12 (Compound example 1-5) is a highly selective and orally active checkpoint kinase 1 (CHK1) inhibitor, demonstrating an in vitro enzyme IC50 of ≤10 nM and a cellular IC50 of ≤50 nM. This compound suppresses the phosphorylation activity of CHK1 kinase, disrupts DNA damage response pathways, and induces tumor cell cycle arrest and apoptosis. CHK1-IN-12 shows promise for cancer research applications.

CX5461 is an rRNA synthesis inhibitor with oral activity that inhibits Pol I-driven rRNA transcription. CX5461 activates the DNA damage response and has antitumor activity in tumors such as ovarian cancer.

PDIC-NN dimethanesulfonate (PDIC-NS) is a STING activator with anticancer properties. It increases the levels and stability of endogenous cyclic dinucleotides (CDN). PDIC-NN dimethanesulfonate triggers a burst of reactive oxygen species (ROS) and causes significant mitochondrial damage. It induces apoptosis and inhibits DNA replication. Additionally, it activates the cGAS-STING signaling pathway, enhancing the immunogenicity of tumor cells and triggering a strong innate immune response.

MDOLL-0286 is a selective inhibitor of Poly(ADP-ribose) Glycohydrolase (PARG), specifically targeting ARH3 with an IC50 value of 2.3 μM. It inhibits the poly(ADP-ribose) hydrolytic activity of ARH3 on cellular substrates and can suppress the DNA damage response. MDOLL-0286 is applicable in cancer research.

Isogranulatimide is a selective inhibitor of checkpoint kinase 1 (Chk1), with an IC50 of 0.1 μM. It can inhibit the G2/M checkpoint and suppress the growth of p53-mutant tumor cells. Isogranulatimide holds potential for research in tumors associated with DNA damage response.

DD-CIP2 is a DNA damage inducer that triggers significant DNA damage, cell cycle arrest, and apoptosis by modulating DNA damage response pathways. It demonstrates notable antitumor efficacy without apparent toxicity at well-tolerated doses in vivo. Its exceptional cytotoxicity against a range of cancer cell lines from hematological and solid tumors is independent of their BRCA1/2 status. DD-CIP2 can be utilized in research on small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC).

Ceritinib-platinum(IV)-4-phenylbutyrate (complex 7) is a Ceritinib-conjugated Platinum(IV) prodrug with anticancer properties. It can induce S phase arrest, DNA damage response, and apoptosis. In cancer cell models, Ceritinib-platinum(IV)-4-phenylbutyrate exhibits cytotoxicity, immune activation, and anti-invasion effects. This compound is applicable in cancer research, such as in non-small cell lung cancer (NSCLC).

Mono N-Desmethyl Disperse Polyester Dark Blue is a bioreductive agent activated under hypoxic conditions. Once inside cells, it converts to its active form, generating reactive oxygen species (including DNA) capable of damaging cellular components. This damage can potentially lead to cell death, especially in hypoxic cancer cells under stress. It has also been shown to inhibit the activity of hypoxia-inducible factor 1 (HIF-1), a key regulator of the cellular response to low oxygen levels.

DN1679 is a potent, selective, and orally active CRBN-dependent dual degrader of CDK12/13 PROTAC. It exhibits DC50 values for CDK12/13 at 8.8/9.8 nM in MDA-MB-231 cells, 5.1/6.4 nM in MDA-MB-157 cells, and 17.2/15.8 nM in MDA-MB-468 cells. DN1679 downregulates mRNA levels of DNA damage response genes such as ATM, ATR, BRCA1, and RAD51. When used in combination with Olaparib, DN1679 shows a significant synergistic anti-tumor effect. It is applicable in research on triple-negative breast cancer.

NU 9056 is an effective and selective inhibitor of KAT5 histone acetyltransferase with an IC50 of 2 µM. NU 9056 blocks DNA damage response and inhibits protein acetylation in prostate cancer cell lines.

Ryuvidine is a dual inhibitor of KDM5A and SETD8, an inducer of the DNA damage response with potential anticancer activity, inhibition of H4K20 methylation, and inhibition of CDK4, and can be used to study breast cancer and erythroplasia.

DDRI-18 is a novel small molecule inhibitor that regulates the DNA damage response with sensitizing and anticancer activities, inhibits non-homologous end-joining (NHEJ) DNA repair and enhances the cytotoxicity of anticancer DNA damage compounds.

BMVC4 is a G-quadruplex stabilizer. BMVC4 induces senescence by activation of pathways of response to DNA damage that was independent of its telomerase inhibitory activity.

Bardoxolone (CDDO) is a synthetic oleanane triterpenoid that blocks the cellular synthesis of inducible nitric oxide synthase and inducible COX-2 in INF-γ-activated mouse macrophages with an IC50 value of 0.4 nM. By suppressing reactive oxygen and nitrogen species (ROS/RNS) formation, it promotes the cellular control of ROS/RNS levels that would lead to DNA damage associated with tumorigenesis. In various Y cell lines, Bardoxolone has been shown to specifically inhibit proliferation and induce apoptosis. Mechanism studies revealed that Bardoxolone is a ligand for peroxisome proliferator-activated receptor γ, and also that it induces genes regulated by Nrf2, including heme oxygenase-1 and eotaxin-1, which play a role in antioxidant response element signaling activity.