DNA Damage/DNA Repair

<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>

<p>NU5455 is a potent DNA-PKcs inhibitor, oral, boosts doxorubicin in liver tumors, amplifies topoisomerase inhibitors, no adverse 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>Edotecarin is a potent topoisomerase I inhibitor. It can decrease single-strand DNA cleavage (IC50: 50 nM).</p>

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

<p>MC3138 is a selective SIRT5 activator showing anti-tumor effects in PDAC cells.</p>

<p>ATM Inhibitor -2 is a potent and selective inhibitor of ATM (IC50&lt;1 nM).</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>Karenitecin (Cositecan) is an inhibitor of topoisomerase I. It has potent anti-cancer activity.</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>(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>(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>Pparδ agonist 5 is a selective, orally active PPARδ agonist with an EC50 of 0.335 μM and better selectivity than GW0742.</p>

<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>

<p>CZ-48 is a DNA topoisomerase inhibitor.</p>

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

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

<p>KU 59403 is an effective ATM inhibitor (IC50: 3 nM, 9.1 μM, and 10 μM for ATM, DNA-PK, and PI3K, respectively).</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>Compound 5h (Topoisomerase I/II inhibitor 7) is a Topoisomerase I/II inhibitor.</p>

<p>ATR-IN-19 (Compound 15 R-configure) is an ATR inhibitor [1].</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>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>ATR-IN-12, a potent ATR kinase inhibitor with IC50 of 0.007 μM, shows promise for drug development.</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>ATR-IN-14: potent ATR kinase inhibitor; 98.03% inhibition at 25 nM; IC50 of 64 nM in LoVo cells.</p>

<p>WSD0628 is a brain-penetrant and potent ATM inhibitor with a significant radiosensitizing effect [1].</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>Topoisomerase II inhibitor 18 (Compound IV), a Quinoxaline derivative, exhibits an IC 50 of 7.5 μM in inhibiting topoisomerase II. It impedes PC-3 cell proliferation, arrests the cell cycle at the S phase, and induces apoptosis. Moreover, this compound demonstrates substantial antitumor activity against cancer [1].</p>

<p>PPARγ agonist17 (Compound C1) is an orally active PPARγ agonist. It enhances PPARγ activity, arrests the cell cycle of HT-29 cells at the G2/M phase, inhibits cell migration, and induces apoptosis. PPARγ agonist17 exhibits broad-spectrum antiproliferative activity against cancer cells with relatively low toxicity to normal cells and does not cross the blood-brain barrier.</p>

<p>Anti-NASH agent 2 (compound 21) is an inhibitor of neolipogenesis activity and α-SMA gene expression. It improves hepatic steatosis, edema, inflammatory infiltration, and liver fibrosis in NASH mouse models.</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>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>ATRkinase-IN-2 (Compound I-G-27) is an inhibitor of the ATR protein kinase, with a Ki value ranging from 0.01 to 1 μΜ. It is utilized in tumor 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>TP3011 is a potent topoisomerase I inhibitor equipotent as SN38 and is an active metabolite of CH-0793076.</p>

<p>Sirtuin-IN-2 (compound 20) is an inhibitor of Sirtuin5, a key target in leukemia and breast cancer.</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>

DLK-IN-1: Oral DLK (MAP3K12) inhibitor, Ki=3nM, effective in Alzheimer's model, CNS permeable, well-tolerated with sustained brain levels.

<p>ATR-IN-11, a potent ATR kinase inhibitor, shows promise as a lead for DNA damage response-targeted cancer drugs.</p>

<p>Bizelesin, a synthetic antineoplastic agent, binds DNA, disrupts replication, triggers cell-cycle arrest, and induces senescence.</p>

<p>KU-60019 is a specific inhibitor of ATM kinase (IC50: 6.3 nM).</p>

<p>Simmitecan hydrochloride is a camptothecin derivative, a topoisomerase I inhibitor with anticancer activity, which can be used to study is solid tumors.</p>

<p>BAY-8400 is an orally active, potent and selective DNA-dependent protein kinase ( DNA-PK ) inhibitor ( IC 50 =81 nM) which shows synergistic efficacy in</p>

<p>OBI-3424, a highly selective prodrug, is converted by aldo-keto reductase family 1 member C3 (AKR1C3) to a potent DNA-alkylating agent.</p>

<p>Phenanthriplatin, also known as cis-[Pt(NH3)2-(phenanthridine)Cl]NO3, is a new drug candidate. It belongs to a family of platinum(II)-based agents which includes cisplatin, oxaliplatin and carboplatin. Phenanthriplatin Acts As a Covalent Poison of Topoiso</p>

<p>NSC61610 is anti-inflammatory that activates PPARγ in vitro via LANCL2 and adenylate cyclase/cAMP-dependent pathways, thereby improving experimental colitis.</p>

<p>YF438 is an HDAC inhibitor that demonstrates potent anti-cancer activity both in vitro and in vivo. It inhibits the growth and metastasis of triple-negative breast cancer (TNBC) cells by blocking the interaction between HDAC and MDM2, inducing the dissociation of MDM2 from MDMX, and promoting the degradation of MDM2.</p>

<p>Zabofloxacin hydrochloride is a potent and seletive bacterial type II and IV topoisomerases inhibitor, has excellent activity against gram-positive pathogens including Steptococcus aureus, Streptococcus pyogenes and S.pneumonia.</p>

<p>Merbarone is a Type II DNA topoisomerase inhibitor. Merbarone inhibits the catalytic activity of human topoisomerase IIalpha by blocking DNA cleavage. Merbarone induces activation of caspase-activated DNase and excision of chromosomal DNA loops from the n</p>

<p>SR-4370 is an HDAC inhibitor. SR- 4370 exhibited IC50 values of 0.5 μM, 0.1 μM and 0.06 μM towards HDAC1, HDAC2 and HDAC3, resp.</p>

<p>Fotemustine: antineoplastic, chloroethylates DNA, blocks synthesis, causes cell arrest/apoptosis, lipophilic, crosses blood-brain barrier.</p>

<p>Mavodelpar free acid (REN001 free acid) is an selective agonist of PPARδ.</p>

<p>Antitumor Agent-104 (Compound 9) serves as an antineoplastic by impeding DNA repair mechanisms in tumor cells, primarily through the inhibition of PARP1 enzyme</p>

<p>MDL-811, an allosteric activator of SIRT6, markedly enhances the deacetylation of histone H3 at lysine residues 9, 18, and 56 (H3K9Ac, H3K18Ac, and H3K56Ac),</p>

<p>ATR-IN-24 (Compound 1) is an ATR inhibitor with demonstrated anticancer activity [1].</p>

<p>Lerzeparib is a PARP (ADP-ribose polymerase) inhibitor that exhibits antineoplastic activity [1].</p>

<p>PARP7-IN-16 free base is the freebase form of PARP7-IN-16. As a selective oral inhibitor of PARP-1/2/7, it demonstrates IC50 values of 0.94, 0.87, and 0.21 nM, respectively. This compound is utilized in the research of breast and prostate cancer.</p>