DNA Damage/DNA Repair

<p>KPZ560, a potent HDAC 1 and HDAC 2 inhibitor, exhibits IC50 values of 12 nM and 68 nM, respectively.</p>

<p>Nesuparib, a potent PARP/TNKS1 inhibitor, has antitumor properties and potential for treating various diseases.</p>

<p>ATR-IN-18: oral ATR inhibitor, IC50 0.69 nM; halts LoVo cell growth, IC50 37.34 nM; anti-tumor.</p>

<p>10-Nitrolinoleate, a nitration product of linoleate, modulates PPARγ, enhancing glucose uptake, and aids in muscle relaxation via NO/cGMP pathway.</p>

<p>(S)-Ceralasertib: Potent, selective ATR inhibitor with strong preclinical physicochemical and PK profiles.</p>

<p>Lexitropsin 1 is a new anticancer drug.</p>

<p>Furegrelate sodium (U-63557A) is an orally active thromboxane synthase inhibitor with an IC50 of 15 nM in platelets.</p>

<p>DNA-PK-IN-10 is a DNA-PK inhibitor utilized in the research of breast cancer and non-small cell lung cancer [1].</p>

<p>PARP7-IN-16 (compound 36) is a potent, selective, and orally active PARP-1/2/7 inhibitor, exhibiting IC50 values of 0.94, 0.87, and 0.21 nM , respectively.</p>

<p>LMP744 hydrochloride (NSC-706744 hydrochloride) is a DNA intercalator and Topoisomerase I (Top1) inhibitor with antitumor activity. </p>

<p>Sipoglitazar, a PPARγ agonist, is used potentially for the treatment of diabetes.</p>

<p>ATR-IN-29, a potent, orally active inhibitor of ATR kinase, exhibits an IC50 of 1 nM and demonstrates antiproliferative activity [1].</p>

<p>Bocodepsin (OKI-179) is a selective, orally active inhibitor of histone deacetylases (HDAC) with demonstrated antitumor efficacy.</p>

Telomerase-IN-1 is a telomerase inhibitor (IC50: 0.19 μM).

<p>PPARγ agonist 7 (Compound 3a) is a highly potent and selective agonist of the peroxisome proliferator-activated receptor gamma (PPARγ).</p>

<p>NT160 is a fluorinated radioactive compound, a potent class IIa histone deacetylase (HDAC) inhibitor, used in the study of neurological diseases.</p>

<p>BO 2367, a topoisomerase inhibitor, is used to suppress the growth of tumor .</p>

<p>Duocarmycin analog-2 is a potent DNA alkylating agent that exhibits antitumor effects and can be used in the synthesis of immunocouplers.</p>

<p>Trovafloxacin: broad-spectrum fluoroquinolone, blocks DNA gyrase/topoisomerase IV and PANX1 channel (IC50=4μM).</p>

<p>DY-46-2 is a DNMT3A inhibitor (IC50: 0.39 ± 0.23 μM) with anticancer activity and is used in cancer and tumor research.</p>

<p>TP0480066 inhibits topoisomerase II, DNA gyrase (IC50=1.1nM), topo IV (IC50=62.89nM), effective against drug-resistant bacteria and N. gonorrhoeae.</p>

<p>Peliglitazar is a activator of α/γ peroxisome proliferator-activated receptor.</p>

<p>SR2595 is an inverse agonist of nuclear receptor PPARγ with an IC 50 of 30 nM [1].</p>

<p>CAY10410 is a PGD2/PGJ2 analog, modified for enhanced PPARγ activity and metabolic stability, non-toxic to SH-SY5Y cells at ≤25μM.</p>

<p>MPI_5a selectively inhibits HDAC6 (IC50=36 nM), slightly affects other HDACs, and blocks acyl-tubulin build-up (IC50=210 nM).</p>

<p>9A1P9, a multi-tail ionizable cationic phospholipid, facilitates membrane destabilization and is applicable for CRISPR-Cas9 gene editing in mice [1].</p>

<p>SRT3657 is a brain-permeable SIRT1 activator, has neuroprotective effect.</p>

<p>DNMT-IN-3 is a DNA Methyltransferase (DNMT) inhibitor with an IC50 of 60 nM against Plasmodium falciparum (Plasmodium), demonstrating antimalarial activity and suitability for malaria-related research [1].</p>

<p>Topoisomerase I Inhibitor 9 (compound 3d), a specific inhibitor of leishmanial topoisomerase IB, exhibits antileishmanial activity, demonstrating an IC50 value</p>

<p>ATR-IN-5 is a potent inhibitor of ATR, a member of the PIKK family of proteins involved in genome stability and DNA damage repair.</p>

<p>ATR-IN-20: potent ATR inhibitor, IC50=3nM; inhibits mTOR, IC50=18nM; selective vs PI3Kα, ATM, DNA-PK; good pharmacokinetics; anticancer.</p>

<p>ATM kinase inhibitor with 0.6 nM IC50, &gt;600-fold selective, enhances irinotecan effects, oral use.</p>

<p>Topoisomerase IIα-IN-8 (compound 15) serves as a modest inhibitor of human DNA topoisomerase IIα (htIIα), exhibiting an inhibitory concentration (IC50) of 462 ± 38.0 μM [1].</p>

<p>U-46619 is an effective thromboxane A2 (TXA2) agonist and a thromboxane A2 analog (endoperoxide), capable of inducing contraction in the aortic smooth muscle (</p>

<p>Pparδ agonist 1 is an agonist of PPAR-δ(EC50 of 5.06 nM).</p>

<p>Zabofloxacin inhibits bacterial topoisomerases II/IV, effectively targeting gram-positive pathogens like S. aureus and S. pneumoniae.</p>

<p>Gsk-3484862 is a non covalent inhibitor of DNA methyltransferase DNMT1 with anticancer activity.</p>

<p>ATR-IN-13 is a potent inhibitor of ATR kinases (IC50: 2 nM) and can be used to study ATR kinase-mediated diseases (e.g. proliferative diseases, cancer).</p>

<p>ARN-21934 inhibits human topoisomerase II α/β; IC50=2μM; stronger than Etoposide (IC50=120μM) in DNA relaxation.</p>

<p>XY-4, a derivative of 1-palmitoyl lysophosphatidic acid (1-palmitoyl LPA094) and an agonist of peroxisome proliferator-activated receptor γ (PPARγ), effectively</p>

<p>K-756 is a direct and selective inhibitor of tankyrase (TNKS), which inhibits the ADP-ribosylation activity of TNKS1 (IC50 = 31 nM) and TNKS2 (IC50 = 36 nM).</p>

<p>Ambamustine (PTT 119): a tripeptide nitrogen mustard, DNA inhibitor/alkylator with antitumor properties, researched for various disorders.</p>

<p>ATR-IN-8 is a potent inhibitor of ATR. ATR-IN-8 has shown potential research value in cancer diseases.</p>

<p>Oxamflatin (Metacept-3) is a selective histone deacetylase (HDAC) inhibitor with an alkyne group capable of azide-alkyne cycloaddition reactions (CuAAc).</p>

<p>LCB-2853 is a potent thromboxane A2/prostaglandin H2 (TXA2/PGH2) receptor antagonist with antiplatelet aggregation, antivasospasm, and antithrombotic effects.</p>

<p>GNE-8505 is an orally available inhibitor of Dual leucine zipper kinase (DLK).</p>

<p>Camonsertib (RP-3500) is a novel, potent and selective ATR kinase inhibitor (ATRi) that exhibits potent antitumor effects with an IC50: 1.00 nM in biochemical assays.Cost-effective and quality-assured.</p>

<p>Lartesertib (ATM Inhibitor-5) is an inhibitor of the serine/threonine protein kinase ATM with potential anticancer activity and can be used to study lung cancer</p>

<p>CGS 15435: potent TxA2 synthase inhibitor, IC50=1 nM; less selective for PGI2 synthase, COX, and liposynthase.</p>

<p>E7016 (GPI 21016) is an orally available PARP inhibitor. E7016 inhibits of DNA repair. E7016 can enhance tumor cell radiosensitivity in vitro and in vivo.</p>

<p>AZ31 is an ATM inhibitor with potency, high selectivity, and oral activity.AZ31 inhibits ATM enzymes, intracellular ATM, with IC50 values of &lt;1.2 nM and 46 nM,</p>

<p>IACS-52825 is a DLK inhibitor that reverses para-mechanical aberrant pain in a CIPN mouse model and can be used to study neurological disorders.</p>

<p>PARP-1-IN-4 is a potent PARP-1 inhibitor with potential see anti-tumor activity, and inhibition of PARP-1 may be used in cancer development.</p>

<p>Ragaglitazar(NNC-61-0029) is a potent dual activator of PPARγ and PPARα.Cost-effective and quality-assured.</p>

<p>SP-C01 is an orally active soluble epoxide hydrolase (sEH) inhibitor and a partial agonist of PPARγ. It can inhibit the phosphorylation of Ser273.</p>

<p>15-keto-Prostaglandin E2, an endogenous metabolite, inhibits STAT3 activation through binding to Cys259 and regulates breast cancer cell growth and progression.</p>

<p>Topoisomerase inhibitor 5 (compound 158) is an inhibitor of bacterial topoisomerase, with a minimum inhibitory concentration of 0.125 μg/mL, and exhibits anti-tuberculosis activity.</p>

<p>E-3030 free acid, a PPAR agonist, lowers blood glucose, triglycerides, and insulin; boosts adiponectin; reduces apo C-III; and raises lipoprotein lipase.</p>

<p>PPARα agonist 1 is a complete and potent PPARα agonist.</p>

<p>SIRT6 activator2 (compound 31) is a sirtuin6 activator known for its anti-lipid accumulation properties. It significantly downregulates LXR, SREBP-1c, and their target genes, making it valuable for research into lipid metabolism-related diseases.</p>

<p>PARP1/2-IN-4 (compound 3) is an inhibitor of PARP1/2.</p>

<p>ATM Inhibitor-1 is a highly potent, selective and orally active ATM inhibito (IC50: 0.7 nM) anti-tumor activity.</p>

<p>ATRkinase-IN-3 (Compound I-G-28) is an inhibitor of the ATR protein kinase, exhibiting a Ki value ranging from 0.01 to 1 μM, and is utilized in cancer research.</p>

<p>Anti bacterial agent 236 (Compound 4l), an orally effective inhibitor of DNA gyrase and topoisomerase IV (with IC50 values of 3.2 and 300 nM in Staphylococcus aureus, respectively), exhibits broad-spectrum antibacterial activity. It also demonstrates favorable pharmacokinetic properties in mice.</p>

<p>TMU 35435 is an inhibitor of histone deacetylases (HDAC). It enhances radiosensitivity by inducing the accumulation of misfolded proteins and autophagy (autophagy) in TNBC, and inhibits the NHEJ pathway through ubiquitination of the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs).</p>

<p>(Rac)-RG108 (NSC401077) is an inhibitor of DNMT1, effectively blocking DNA methyltransferases.</p>

<p>LP-284 is a DNA alkylating agent effective against solid tumors and hematologic cancers like MCL.</p>

<p>G-631 acts as a selective tankyrase inhibitor, effectively hindering tankyrase auto-PARsylation (poly ADP ribosylation) at an IC 50 of 7 nM and suppressing the Wnt signaling pathway. This compound also demonstrates favorable pharmacokinetic properties in mice.</p>

<p>PPARγ agonist 1 is a potent agonist of PPARγ that efficiently activates hPPARγ without causing full agonism, thereby avoiding adverse effects.</p>

<p>KSQ-4279 (gentisate) (Compound Formula I) serves as an effective inhibitor of USP1 and a selective inhibitor of PARP1. This compound shows promise for use in cancer research.</p>

<p>L2H2-6OTD is a telomerase inhibitor with G-quadruplex loops; IC50: 15 nM.</p>

<p>Carbacyclin, a PGI2 analog, is a prostacyclin (PGI2) receptor agonist and vasodilator with potent inhibitory platelet aggregation.</p>

<p>DNA Crosslinker 4 binds DNA's minor groove, inhibits NCI-H460, A2780, MCF-7 cancer cells, and is used in cancer research.</p>

<p>Topoisomerase II inhibitor 6, a potent tryptanthrin derivative, blocks G2 phase in CCRF-CEM cells, induces DNA breaks, and may be used for cancer research.</p>

<p>2-Ethylhexyl diphenyl phosphate is an organophosphorus flame retardant (OPFRs) and acts as a PPARG agonist (EC20: 2.04 µM). Additionally, it inhibits the transcriptional activity of ERRγ (IC50: 1.3 µM) and enhances the expression of 3β-HSD1, human chorionic gonadotropin (hCG), and progesterone secretion. This compound is applicable in studies related to female reproduction and fetal development.</p>

<p>SARS-CoV-2 nsp14-IN-1 inhibits Nsp14 Mtase with an IC50 of 0.061 μM, affecting multiple substrates.</p>

PPARγ phosphorylation inhibitor 1 (Compound 10) is a potent PPARγ binding agent (IC50: 24 nM) with antidiabetic effects.

<p>ATM Inhibitor-3 selectively inhibits ATM (IC50: 0.71 nM), targets PI3K kinase family, and is metabolically stable.</p>

<p>Intoplicine is an inhibitor of DNA topoisomerase I and II.</p>

<p>TDI-015051 is an orally active inhibitor of SARS-CoV-2 non-structural protein 14 (SARS-CoV-2 NSP14) with an IC50 of ≤0.15 nM. It effectively inhibits SARS-CoV-2 NSP14 in Huh-7.5 cells (EC50=11.4 nM) and A549 cells expressing ACE2-TMPRSS2 (EC50=64.7 nM). Additionally, TDI-015051 suppresses other coronaviruses such as α-hCoV-NL63, α-hCoV-229E, and β-hCoV-MERS with IC50 values of 1.7, 2.6, and 3.6 nM, respectively. This compound inhibits viral RNA methylation and replication by binding to a stable SAH-cap pocket and demonstrates anti-infection activity in mouse models.</p>

<p>Cas9-IN-1 is a potent inhibitor of Cas9 with an IC50 value of 7.02 μM. Cas9-IN-1 acts by binding apo-Cas9 and blocking the formation of the Cas9:gRNA complex.</p>

HDAC6-IN-51 (Compound 7e) is a selective inhibitor of HDAC6, exhibiting an IC50 value of 42.9 nM. This compound demonstrates effective anti-pulmonary fibrosis activity.

<p>Compound 1a inhibits Topoisomerase I/II, shrinks mouse liver tumors, IC50: 6.83/9.82 μM for LM9/Huh7 cells.</p>

Gimatecan (STI481) is a potent topoisomerase I inhibitor. Gimatecan is an orally bioavailable camptothecin analogue with antitumor activity.

<p>DNA-PK-IN-15 (compound 6) acts as an inhibitor of DNA-PK, exhibiting an IC50 value of 0.08 nM.</p>

<p>ATMInhibitor-11 (Compound 1) is an inhibitor of ATM with an IC50 of 0.32 nM. It also inhibits KAP1 phosphorylation with an IC50 of 0.97 nM. This compound exhibits high exposure in the brain, heart, and plasma of ICR mice. Furthermore, ATMInhibitor-11 demonstrates antitumor activity in the NCI-H441 xenograft mouse model.</p>

<p>GSK1820795A: Telmisartan analog, selective hGPR132a antagonist, blocks yeast activation by N-acylamides, angiotensin II antagonist, partial PPARγ agonist.</p>

<p>Topotecan acetate is an inhibitor of topoisomerase.</p>

<p>DNA-PK-IN-6 inhibits DNA-PKcs, disrupting tumor DNA repair and triggering apoptosis; enhances radiotherapy and targets various tumors (WO2021197159A1).</p>

<p>DNA-PK-IN-2 is an inhibitor of the DNA-PK enzyme complex, useful in cancer research.</p>

<p>Atiratecan (TP300), a CH0793076-based camptothecin prodrug, combats BCRP+/- tumors; doesn't affect AChE.</p>

<p>PARP1-IN-30 is a specific and effective PARP1 inhibitor with cytotoxic properties. It precisely inhibits PARP1 in tumor cells lacking breast cancer 1 protein (BRCA1) or BRCA2. PARP1-IN-30 holds potential for use in cancer research.</p>

<p>DNA-PK-IN-8: Potent, selective oral DNA-PK inhibitor, IC50 = 0.8 nM, boosts anti-cancer effects with Doxorubicin.</p>

<p>Namitecan is an effective inhibitor of topoisomerase I. It has antitumor property.</p>

<p>DNA Crosslinker 1 binds DNA minor groove with 1.1°C affinity increase; used in cancer research.</p>

<p>Compound 1: a DNA minor groove binder with 1.4°C ΔTm; useful in cancer research.</p>

<p>Topoisomerase II inhibitor 5 (Compound E24) is a DNAtopoisomerase II inhibitor with anticancer effects.</p>

<p>TH1338 is an orally active camptothecin derivative with significant blood-brain barrier permeability and cytotoxicity, used in cancer research.</p>

<p>HDAC8-IN-12 (compound 5k), a non-hydroxamic acid derivative, serves as a selective HDAC8 inhibitor with an IC 50 of 0.12 nM and demonstrates potent efficacy against breast cancer. This compound enhances anti-tumor immunity by activating T cells, elevating M1 macrophage levels, and reducing M2 macrophage proportions. In an orthotopic mouse model of breast cancer, HDAC8-IN-12, administered at 50 mg/kg, effectively suppresses tumor growth.</p>

<p>Potent DNA crosslinker 2 binds minor groove, increases Tm by 1.2°C, and inhibits NCI-H460, A2780, MCF-7 cancer cells.</p>

<p>Levofloxacin mesylate is an orally active antibiotic effective against both Gram-positive and Gram-negative bacteria. It inhibits DNA gyrase and topoisomerase IV enzymes. Levofloxacin mesylate is employed in research related to chronic periodontitis, airway inflammation, and BK viremia. Additionally, it possesses anti-Orthopoxvirus activity.</p>

<p>PPARα/γ agonist 1 is a potent and dual PPARα/γ partial agonist which is a promising prototype for the research of dyslipidemia and diabetes.</p>

<p>Lys(CO-C3-p-I-Ph)-O-tBu, a pharmacokinetic modifier (PK modifier), enhances the pharmacokinetic properties of PSMA ligand molecules by increasing their residence time in plasma through improved binding to albumin and reducing absorption by the salivary glands, potentially extending the active compound's half-life. Moreover, Ac-PSMA-trillium is an effective PSMA-targeting compound for various biological applications when modified with different radioactive isotopes. When labeled with 111 In, it serves as a DOTA chelating agent and imaging agent. Alternatively, when labeled with 225 Ac, it acts as a Macropa chelator for targeted radionuclide therapy (TRT) in researching metastatic castration-resistant prostate cancer (mCRPC) [1] [2].</p>