DNA Damage/DNA Repair

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

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

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

<p>LP-284 is a DNA alkylating agent effective against solid tumors and hematologic cancers like MCL.</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>DNA-PK-IN-8: Potent, selective oral DNA-PK inhibitor, IC50 = 0.8 nM, boosts anti-cancer effects with Doxorubicin.</p>

<p>Topoisomerase II inhibitor 5 (Compound E24) is a DNAtopoisomerase II inhibitor with anticancer effects.</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>DNA-PK-IN-6 inhibits DNA-PKcs, disrupting tumor DNA repair and triggering apoptosis; enhances radiotherapy and targets various tumors (WO2021197159A1).</p>

<p>MC3138 is a selective SIRT5 activator showing anti-tumor effects in PDAC cells.</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>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>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>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>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>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>PARP1/2-IN-4 (compound 3) is an inhibitor of PARP1/2.</p>

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

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

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

<p>CZ-48 is a DNA topoisomerase inhibitor.</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>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>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>Pparδ agonist 5 is a selective, orally active PPARδ agonist with an EC50 of 0.335 μM and better selectivity than GW0742.</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>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>Carbacyclin, a PGI2 analog, is a prostacyclin (PGI2) receptor agonist and vasodilator with potent inhibitory platelet aggregation.</p>

<p>ATM Inhibitor -2 is a potent and selective inhibitor of ATM (IC50&lt;1 nM).</p>

<p>ATR-IN-14: potent ATR kinase inhibitor; 98.03% inhibition at 25 nM; IC50 of 64 nM in LoVo cells.</p>

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

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

<p>SPR719 is an inhibitor of gyrase B, has bactericidal 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>PPARγ agonist 2 is a highly effective compound that acts as a partial agonist for PPARγ.</p>

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

<p>WSD0628 is a brain-penetrant and potent ATM inhibitor with a significant radiosensitizing effect [1].</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>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>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>ATR-IN-17 is a potent inhibitor of ATR kinase with good anti-cancer effects in LoVo cells (IC50: 1 nM).</p>

<p>Karenitecin (Cositecan) is an inhibitor of topoisomerase I. It has potent anti-cancer activity.</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>Edotecarin is a potent topoisomerase I inhibitor. It can decrease single-strand DNA cleavage (IC50: 50 nM).</p>

<p>NU5455 is a potent DNA-PKcs inhibitor, oral, boosts doxorubicin in liver tumors, amplifies topoisomerase inhibitors, no adverse effects.</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>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>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>