Dano de DNA/Reparo de DNA

<p>Compound 12C, with altered cap groups, shows wide-range enzyme inhibition; 9m and 9q target HDAC6 specifically.</p>

<p>HDAC/BET-IN-1 inhibits HDAC1 (IC50: 0.163 μM), HDAC6 (IC50: 0.067 μM), BRD4 (Ki: 0.076 μM), and fights leukemia.</p>

<p>Tankyrase-IN-5 (Compound 30f), structurally related to MSC2504877, effectively inhibits tankyrase isoforms TNKS1 and TNKS2, with half-maximal inhibitory</p>

<p>CM-675 is a dual inhibitor of phosphodiesterase 5 (PDE5) and class I histone deacetylases (IC50s: 114 nM and 673 nM for PDE5 and HDAC1) with the potential to</p>

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

<p>PARP7-IN-15 (Compound 18) is a potent PARP7 inhibitor exhibiting an IC50 of 0.56 nM and demonstrates antitumor activity [1].</p>

<p>Epigenetic factor-IN-1 (40569Z) is an epigenetic factor inhibitor that exhibits potent binding affinity for SIRT7.</p>

<p>PR-104A is a hypoxia-targeted anticancer agent.</p>

<p>Exatecan TFA, a methylpropanamide-modified derivative of the common ADC cytotoxin Exatecan, serves as a DNA topoisomerase I inhibitor with an IC50 of 2.2 μM (0.</p>

<p>7-Deaza-2′-deoxyguanosine 5′-triphosphate (7-Deaza-2'-dGTP), a nucleotide analogue, functions as a telomerase inhibitor with an IC50 value of 11 μM [1].</p>

<p>SIRT6-IN-3 (compound 8a), a selective SIRT6 inhibitor (IC50 = 7.49 μM), impedes the proliferation of pancreatic ductal adenocarcinoma (PDAC) cells and prompts</p>

<p>ATR-IN-21, also known as compound 60, is a potent inhibitor of ATR, exhibiting an IC50 of less than 1000 nM [1].</p>

<p>Prostaglandin B3 (PGB3) is a secondary alcohol belonging to the prostaglandin B class, characterized by its relatively low affinity for human PPARγ, exhibiting a K_i value greater than 1 mM, in contrast to PGB1 and PGB2, which have K_i values of 26.28 ± 8.7 μM and 77 ± 37.7 μM, respectively [1].</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>PPARγ agonist 7 (Compound 3a) is a highly potent and selective agonist of the peroxisome proliferator-activated receptor gamma (PPARγ).</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>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>CAY10410 is a PGD2/PGJ2 analog, modified for enhanced PPARγ activity and metabolic stability, non-toxic to SH-SY5Y cells at ≤25μM.</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>ATR-IN-8 is a potent inhibitor of ATR. ATR-IN-8 has shown potential research value in cancer diseases.</p>

<p>Makaluvamine A comes from the fruiting bodies of Didymium bahiense that act as active anti-cancer agents and DNA topo II inhibitors.</p>

<p>SU-11752 selectively inhibits DNA-PK by competing with ATP, enhances ionizing radiation sensitivity without affecting cell cycle or ATM activity.</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>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>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>ATM kinase inhibitor with 0.6 nM IC50, &gt;600-fold selective, enhances irinotecan effects, oral use.</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>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>

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

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

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

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

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

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

<p>Furegrelate sodium (U-63557A) is an orally active thromboxane synthase inhibitor with an IC50 of 15 nM in platelets.</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>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>Nesuparib, a potent PARP/TNKS1 inhibitor, has antitumor properties and potential for treating various diseases.</p>

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

<p>ZL-2201 is a potent inhibitor of DNA-PK, demonstrating an IC50 value of 1 nM.</p>

<p>BMS-250749 is a fluoroglycosylated fluoroindolocarbazole, it has antitumor activity.</p>

<p>ATR-IN-6: potent ATR kinase inhibitor for cancer treatment, referenced in patent WO2021233376A1 as compound A22.</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>CGS 15435: potent TxA2 synthase inhibitor, IC50=1 nM; less selective for PGI2 synthase, COX, and liposynthase.</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>Ragaglitazar(NNC-61-0029) is a potent dual activator of PPARγ and PPARα.Cost-effective and quality-assured.</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>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>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>

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

<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>Topoisomerase I inhibitor 8, a hexacyclic analogue of camptothecin, is also a potent inhibitor of topoisomerase I and is toxic to tumour cells.</p>

<p>PPARα/δ agonist 3 (Compound 8) is an orally active PPAR agonist capable of activating PPARα, PPARδ, and PPARγ, with EC50 values of 5.6 nM, 3.4 nM, and 1278 nM, respectively. It exhibits anti-cholestatic activity in mouse models of cholestatic liver disease induced by ANIT or CDCA.</p>

<p>PPARγ-IN-5 (Compound A3) is an inhibitor of PPARγ. In liver cells, it reduces lipid accumulation and shows no significant cytotoxicity in HepG2 cells at a concentration of 400 µM. PPARγ-IN-5 is applicable for research on non-alcoholic fatty liver disease.</p>

<p>O6BTG-C8-αGlu is an O6-methylguanine-DNA methyltransferase (MGMT) inhibitor with an IC50 of 0.45 μM. At a concentration of 0.1 μM, it fully inhibits MGMT in HeLaS3 cells and demonstrates no cytotoxicity even at prolonged high doses (up to 20 μM). This compound is suitable for research on MGMT-related cancers.</p>

<p>Compound 1a inhibits Topoisomerase I/II, shrinks mouse liver tumors, IC50: 6.83/9.82 μM for LM9/Huh7 cells.</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>ATR-IN-17 is a potent inhibitor of ATR kinase with good anti-cancer effects in LoVo cells (IC50: 1 nM).</p>

<p>RU-0415529 is an orally active inhibitor of SARS-CoV-2 non-structural protein 14 (NSP14), with an IC50 of 356 nM. It inhibits viral RNA methylation and replication by stabilizing the cap-binding pocket through SAH binding. Additionally, RU-0415529 exhibits anti-infective activity in mouse models.</p>

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

<p>ATR-IN-12, a potent ATR kinase inhibitor with IC50 of 0.007 μM, shows promise for drug development.</p>

<p>ATR-IN-19 (Compound 15 R-configure) is an ATR inhibitor [1].</p>

<p>ATM Inhibitor-1 is a highly potent, selective and orally active ATM inhibito (IC50: 0.7 nM) anti-tumor activity.</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>DNA-PK-IN-8: Potent, selective oral DNA-PK inhibitor, IC50 = 0.8 nM, boosts anti-cancer effects with Doxorubicin.</p>

<p>Amezalpat is a PPARα antagonist with an IC50 of 58 nM [nanomolar]. Amezalpat also exhibits antitumor activity.</p>

Retelliptine, a DNA topoisomerase II inhibitor, is used potentially for the treatment of cancer.

<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>(R)-Sitafloxacin (DU-6857) is an enantiomer of Sitafloxacin (DU-6859a) and functions as a topoisomerase inhibitor, demonstrating an IC50 of 0.18 μg/mL against DNA gyrase.</p>

<p>Karenitecin (Cositecan) is an inhibitor of topoisomerase I. It has potent anti-cancer activity.</p>

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

<p>(S)-WSD0628 is the S isomer of WSD0628 and serves as an ATM inhibitor, effectively suppressing ATM phosphorylation in MCF-7 cells with an IC50 of less than 100 nM. This compound also demonstrates radiosensitizing activity and is capable of penetrating the blood-brain barrier.</p>

<p>(1S,2R,7S)-Sitafloxacin (DU-6856) is an enantiomer of Sitafloxacin and functions as a topoisomerase inhibitor. As an antibiotic, it demonstrates inhibitory activity against Escherichia coli DNA gyrase (IC50 0.18 μg/mL) and Staphylococcus aureus topoisomerase IV. (1S,2R,7S)-Sitafloxacin exhibits antibacterial properties and is utilized in the study of various bacterial infections.</p>

<p>PARP-1/HDAC-IN-1 is a PARP-1 and HDAC6 inhibitor with anticancer, antimigratory, and antiangiogenic activities and is used in tumor research.</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>

<p>PPARγmodulator-2 (Compound (R)-2n) is a reversible modulator of PPARγ, inhibiting the PPARγ ligand-binding domain (LBD) with an IC50 of 41 nM. It helps lower blood glucose levels, improves glucose tolerance and insulin sensitivity, and demonstrates antidiabetic activity in db/db mouse models.</p>

<p>Compound 5h (Topoisomerase I/II inhibitor 7) is a Topoisomerase I/II inhibitor.</p>

<p>PPARγ agonist 2 is a highly effective compound that acts as a partial agonist for PPARγ.</p>

<p>SPR719 is an inhibitor of gyrase B, has bactericidal activity.</p>

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

<p>DNA-PK-IN-9 (YK6) is a potent DNA-PK inhibitor with an IC50 of 10.47 nM, important in cancer research.</p>

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

<p>TERT activator-2 (Compound 1030) is an activator of telomerase reverse transcriptase (TERT), which enhances the expression levels of TERT within cells. TERT activator-2 is applicable to research related to cellular lifespan and telomere functions.</p>

<p>Compound 1: a DNA minor groove binder with 1.4°C ΔTm; useful 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>

OSUAB-0284 is an inhibitor of bacterial topoisomerase. It exhibits significant activity against staphylococci, particularly methicillin-resistant Staphylococcus aureus (MRSA). The compound exerts its antibacterial effect by inhibiting bacterial topoisomerase and may be used in research on infections caused by drug-resistant bacteria, including MRSA.

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

<p>ATM Inhibitor -4: selective, potent (IC50: 0.32 nM), inhibits PI3K family, stable, stops mTOR at 1 μM.</p>

<p>L2H2-6OTD is a telomerase inhibitor with G-quadruplex loops; IC50: 15 nM.</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>DNA Crosslinker 4 binds DNA's minor groove, inhibits NCI-H460, A2780, MCF-7 cancer cells, and is used in cancer research.</p>

<p>NU5455 is a potent DNA-PKcs inhibitor, oral, boosts doxorubicin in liver tumors, amplifies topoisomerase inhibitors, no adverse effects.</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>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>ATR-IN-11, a potent ATR kinase inhibitor, shows promise as a lead for DNA damage response-targeted cancer drugs.</p>

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