adducts

N-tert-butyl-α-Phenylnitrone ((Z)-N-benzylidene-2-Methylpropan-2-aMine oxide) inhibits COX2 catalytic activity. N-tert-butyl-α-Phenylnitrone((Z)-N-benzylidene-2-Methylpropan-2-aMine oxide) possesses potent reactive oxygen species scavenging, anti-inflammatory, neuroprotective, anti-aging, and anti-diabetic activities, and can penetrate the blood-brain barrier.

Cisplatin (CDDP) is a chemotherapeutic agent with antitumor activity and is a classic DNA crosslinker. It inhibits DNA synthesis and induces DNA damage in cancer cells by forming DNA adducts, ultimately leading to cell death. In addition, Cisplatin can activate ferroptosis and induce autophagy. In animal studies, it is commonly used to establish models of chronic kidney injury and acute renal failure.

Azoxymethane (AOM) is a colon-specific carcinogen that induces DNA damage and forms DNA adducts, and is commonly used to establish mouse models of colorectal cancer.

SG2057 (DRG16), a potent antitumor agent, is a pyrrolobenzodiazepine (PBD) dimer connected by a pentyldioxy linkage. This compound selectively binds to the minor groove of DNA, forming both interstrand and intrastrand cross-linked adducts, contributing to its high antitumor activity.

4-Nitroquinoline 1-oxide (4-NQO) is a chemical carcinogen that induces mutations in bacteria, fungi, and animals through the formation of large amounts of purine adducts.

5-fluoro 203 (NSC-703786) is a cytotoxic molecule leading to cell death by forming DNA adducts. 5-fluoro 203 induces aryl hydrocarbon receptor signaling, and elevates expression of CYP1A1. 5-fluoro 203 treatment of cells also leads to elevation of reactive oxygen species and activation of p38, JNK and ERK.

(Rac)-IBT6A is a racemate of IBT6A, an impurity of Ibrutinib that can be utilized in the synthesis of IBT6A Ibrutinib dimer and IBT6A adduct.

Nitracrine is a 1-nitroacridine derivative and is an effective hypoxia-selective agent in vitro and antitumor drugs. Nitracrine suppresses RNA synthesis and covalently, reversibly binds to DNA but also forms covalent adducts with DNA in vivo. Nitracrine h

PhIP is a heterocyclic aromatic amine (HAA) from cooked meat. It belongs to pyridine heterocyclic amine and is a 2B carcinogen with estrogen activity. PhIP forms adducts with DNA that promote cancer.

Mal-PEG4-VA-PBD is a commonly used linker-toxin conjugate structure in antibody-drug conjugates (ADCs). It consists of Mal for conjugation to antibody thiols, PEG4 as a hydrophilic spacer arm to improve solubility, VA as a dipeptide linker cleavable by lysosomal proteases, and a pyrrolobenzodiazepine (PBD) DNA alkylator as the cytotoxic payload. Mal-PEG4-VA-PBD is cleaved by proteases upon cell entry to release PBD, which then forms covalent adducts with DNA and induces cell death.

α-Hydroxytamoxifen, a metabolite of tamoxifen, reacts with DNA and forms DNA adducts.

N-Nitrosonornicotine, a tobacco-specific nitrosamine, exhibits carcinogenic and mutagenic properties, and is capable of inducing micronuclei in C3A cells. Additionally, N-Nitrosonornicotine can form DNA adducts.

1-Nitropyrene (3-Nitropyrene) is one of the important components of atmospheric pollutants such as tobacco smoke. It is carcinogenic and genotoxic, and can damage mitochondrial function and intracellular redox balance.

Dichloro(bipyridine)platinum is a potent platinum-based antitumor complex and a structural analogue of cisplatin. The incorporation of the bipyridine ligand enhances its lipophilicity and planar stacking ability. The compound interacts with DNA through covalent binding or intercalation, forming cis-Pt-DNA adducts that disrupt DNA replication and transcription. Research indicates that such complexes effectively activate pro-apoptotic signaling pathways and exhibit significant growth inhibition across various cancer cell lines, including those resistant to cisplatin. It serves as a foundational scaffold for developing next-generation metallodrugs in oncology.

Pyrazine diazohydroxide (NSC 361456) sodium is an antineoplastic agent that forms DNA adducts through reactive pyrazine diazo ions. It is used in research for renal cancer, colorectal cancer, melanoma, and leukemia.

HJ03 is an orally bioavailable inducer of DNA damage and ferroptosis (ferroptosis) that can cross the blood-brain barrier. It triggers ferroptosis by enhancing intracellular ROS, Fe2+ accumulation, and lipid peroxidation. HJ03 induces DNA adducts and interstrand crosslinks, hindering DNA replication and transcription, leading to G2/M phase arrest and cell apoptosis (apoptosis). It is applicable for research on glioblastoma multiforme and colorectal cancer.

In epidemiological studies, Aflatoxin B1-N7-guanine serum albumin adducts have been established as biomarkers of dietary aflatoxin exposure.

Iproplatin is a platinum-containing derivative related to cisplatin that binds to DNA to form DNA cross-links and platinum-DNA adducts, thereby causing DNA replication failure and cell death. Compared to cisplatin, iproplatin exhibits greater resistance to inactivation by glutathione.

MeIQx (MeIQx) is a food-derived carcinogen that has been found in high temperature-cooked fish and meats.1It is activated by hydroxylation and subsequent O-acetylationviathe cytochrome P450 (CYP) isoform CYP1A2 and N-acetyltransferase 2, respectively, in UV5 cells expressing the human enzymes to a metabolite that reacts with DNA to form adducts.2MeIQx (200 and 400 ppm in the diet) induces tumor formation in rats.3

DEPMPO is a nitrone that is used to spin trap reactive O-, N-, S-, and C-centered radicals and allow their characterization when used in association with electron spin resonance. It is noted for the stability of adducts formed. DEPMPO can be used in vitro or in vivo, as it crosses lipid bilayer membranes and is a good trapping agent in biological systems. DEPMPO-biotin is a biotinylated form of DEPMPO which retains the outstanding persistency of its adducts. The biotin moiety offers an effective means for monitoring biodistribution in cells, tissues, and organs when used with an avidin-conjugated reporter. Importantly, DEPMPO-biotin binds free radicals, such as S-nitroso groups, on proteins, producing adducts that can be analyzed via the biotin tag. This direct labeling of S-nitrosothiols (SNO) thus serves as an effective alternative to the more cumbersome biotin-switch method for monitoring SNO formation.

Phosphoramide mustard cyclohexanamine is the active metabolite of cyclophosphamide, an alkylating agent that cross-links DNA strands, organizes cell division and causes cell death, and has antitumor activity.

Monohydroxy melphalan is a DNA alkylating agent and a degradation product of melphalan . Monohydroxy melphalan is formed by the hydrolysis of melphalan in aqueous solutions, including cell culture medium and human plasma. It increases the level of DNA adducts in ML-1 myeloblastic leukemia cells in a concentration-dependent manner and induces cytotoxicity with an IC50 value of 28.1 μg/ml.

N'-Nitrosonornicotine is a tobacco-specific N-nitrosamine and carcinogen that has been found in unburned tobacco and cigarette smoke.1It induces the formation of DNA adducts in isolated rat nasal mucosa and esophagus. N'-Nitrosonornicotine induces tumor formation in rat esophagus and nasal cavity, mouse lung, forestomach, and trachea, and hamster trachea and forebrain. Urinary levels of N'-nitrosonornicotine are positively correlated with the risk of esophageal cancer in smokers.2 1.Hecht, S.S.Biochemistry, biology, and carcinogenicity of tobacco-specific N-nitrosaminesChem. Res. Toxicol.11(6)559-603(1998) 2.Yuan, J.-M., Knezevich, A.D., Wang, R., et al.Urinary levels of the tobacco-specific carcinogen N'-nitrosonornicotine and its glucuronide are strongly associated with esophageal cancer risk in smokersCarcinogenesis32(9)1366-1371(2011)

cDPCP is a platinum-containing DNA-crosslinking agent.1Unlike cisplatin or oxaliplatin , cDPCP forms monofunctional DNA adducts. It is transported into cells by organic cation transporter 1 (OCT1) and OCT2, inhibiting proliferation of MDCK cells expressing the human transporters with IC50values of 8.1 and 1.5 μM, respectively. cDPCP inhibits RNA polymerase II-mediated transcription in a reporter assay using HeLa cells. It increases survival in murine S180 sarcoma and P388 leukemia models when administered at doses of 40 and 80 mg/kg, respectively.2 1.Lovejoy, K.S., Todd, R.C., Zhang, S., et al.cis-Diammine(pyridine)chloroplatinum(II), a monofunctional platinum(II) antitumor agent: Uptake, structure, function, and prospectsProc. Natl. Acad. Sci. USA105(26)8902-9807(2008) 2.Hollis, L.S., Amundsen, A.R., and Stern, E.W.Chemical and biological properties of a new series of cis-diammineplatinum(II) antitumor agents containing three nitrogen donors: cis-[Pt(NH3)2(N-donor)Cl]+J. Med. Chem.32128-136(1989)