human topoisomerase i

Top1 inhibitor 1 is a potent inhibitor of human topoisomerase I (Top1)(IC50: 29 nM).

Topoisomerase I, Human (EC 5.99.1.2), is capable of relaxing supercoiled DNA molecules. It can initiate the transient breakage and rejoining of phosphodiester bonds in closed circular DNA supercoils.

Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate functioning as a HER2-targeted topoisomerase I inhibitor, with targeting capability and antitumor activity, employed in research on HER2-positive breast cancer and gastric cancer.

Doxorubicin hydrochloride is an anthracycline antibiotic with cytotoxic and antitumor activity. It is an effective inhibitor of human DNA topoisomerase I and II, with IC50 values of 0.8 μM and 2.67 μM, respectively. In addition to inhibiting DNA topoisomerases, it can reduce the phosphorylation of AMPK and its downstream target, acetyl-CoA carboxylase. Doxorubicin hydrochloride also induces apoptosis and autophagy. In animal studies, it is commonly used to induce models of acute renal failure, chronic kidney injury, and heart failure.

Sophoridine (Dihydro-5-episophocarpine), a natural anticancer drug, has been used in China for decades. A series of novel N-substituted Sophoridinic acid derivatives were synthesized and evaluated for their cytotoxicity with 1 as the lead. The structure-activity relationship indicated that introduction of an aliphatic acyl on the nitrogen atom might significantly enhance the anticancer activity. Among the compounds, 6b bearing bromoacetyl side-chain afforded a potential effect against four human tumor cell lines (liver, colon, breast, and lung). The mechanism of action of 6b is to inhibit the activity of DNA topoisomerase I, followed by the S-phase arrest and then cause apoptotic cell death, similar to that of its parent 1.

Alternariol is a natural product extracted from Etoac that demonstrates anti-inflammatory activity in vitro and in vivo in murine hepatoma cells and in human serum, with additional effects on toll-like receptor signaling and regulation of pro-apoptotic protein expression. Alternariol has been shown to be inactive against methyl transferase enzymes, a feature relevant to its metabolic inactivation profile.

CL2A-SN-38 is a drug-linker conjugate composed of a potent a DNA Topoisomerase I inhibitor SN-38 and a linker CL2A to make antibody drug conjugate (ADC).. CL2A-SN-38 is composed of a potent a DNA Topoisomerase I inhibitor SN-38 and a linker CL2A to make antibody drug conjugate (ADC). CL2A-SN-38 provides significant and specific antitumor effects against a range of human solid tumor types. CL2A is a noncleavable complicated PEG8- and triazole-containing PABC-peptide-mc linker. CL2A is cleavable through pH sensitivity, giving rise to bystander effect, and binds the antibody at a cysteine residue via a disulfide bond. .

Compound AuL9, also known as iNOS/TopoI-IN-1, is a multi-target hybrid molecule possessing anti-tumor, anti-inflammatory, and antioxidant properties. This compound effectively inhibits the growth of MCF-7 and MDA MB-231 breast cancer cells in vitro, exhibiting IC50 values of 3.5 μM and 6.3 μM respectively. It also prompts DNA damage and apoptosis in these cells by inhibiting human topoisomerase I (TopoI) with a K_i of 2.72 μM. Additionally, iNOS/TopoI-IN-1 reduces the expression of iNOS by suppressing the activation of NF-kB, with a K_i of 1.49 μM.

TopoisomeraseI/II inhibitor 6 (compound 3i) acts as an effective inhibitor of topoisomerase I and II, with IC50 values of 4.77 µM and 15 µM, respectively. Additionally, it exhibits antiproliferative activity against the human melanoma cell line LOX IMVI, demonstrating IC50 values of 26.7 µM and 25.4 µM.

UNBS3157 is a novel naphthalimide derivative that is non-hematotoxic and exhibits significant antitumor activity through DNA intercalation and the poisoning of topoisomerase IIalpha. Unlike Amonafide, a related naphthalimide compound that showed activity in Phase II breast cancer trials but did not proceed to Phase III due to dose-limiting myelotoxicity, UNBS3157 has a maximum tolerated dose 3-4 times higher and does not cause hematotoxicity in mice at effective antitumor doses. In vivo models, including (i) L1210 mouse leukemia, (ii) MXT-HI mouse mammary adenocarcinoma, and (iii) human A549 non-small cell lung carcinoma and BxPC3 pancreatic cancer orthotopic models, demonstrate superior efficacy of UNBS3157 compared to Amonafide.

DTS-108 is a prodrug of SN38 (a topoisomerase I inhibitor). It is a conjugate formed by linking SN38 to a human oligopeptide through an esterase-sensitive crosslinker. DTS-108 exhibits anticancer activity against colorectal cancer, lung cancer, and breast cancer.

Topoisomerase I inhibitor 21 (Compound 3e) inhibits Topoisomerase I by stabilizing the enzyme-DNA complex. It exhibits antiproliferative activity in 39 types of human cancer cells (JFCR39), with an average GI50 of 39 nM.

meso-Tetra(4-pyridyl)porphine (Compound 10) is a porphyrin derivative. It acts as a weak inhibitor of human topoisomerase I (Top1), with an EC50 greater than 50 µM. This compound can be utilized in cancer research.

Betulinic acid (ALS-357) is a pentacyclic lupane-type triterpene derivative of betulin (isolated from the bark of Betula alba, the common white birch) which has antiretroviral, antimalarial, and anti-inflammatory properties, as well as a more recently discovered potential as an anticancer agent, by inhibition of topoisomerase.

S39625, an E-ring camptothecin keto analogue, is a stable, potent, and selective topoisomerase I inhibitor without being substrates of drug efflux transporters. Nanomolar concentrations of S39625 induces intense and persistent histone gamma-H2AX. The chem

TAS-103 is a dual inhibitor of DNA topoisomerase I/II, utilized in cancer research.

AuM1Phe, an N-heterocyclic carbene (NHC) metal complex, inhibits both human topoisomerase I activity and actin polymerization. It also impedes the proliferation of MDA-MB-231 breast cancer cells, exhibiting an IC50 value of 1.2 μM [1].

Camptothecin-D5 is a deuterated derivative of Camptothecin (T1123) (CPT), an alkaloid and an inhibitor of DNA topoisomerase I (Topo I) with an IC50 value of 679 nM. Camptothecin (T1123) (CPT) exhibits potent antitumor activity against colorectal, breast, lung, and ovarian cancers by modulating the expression pattern of miRNA and regulating the activity of hypoxia-inducible factor-1α (HIF-1α) in human cancer cells.

Anti-CCL2 (Carlumab)-MC-Vc-PAB-SN38 is an antibody-drug conjugate (ADC) composed of the human anti-CCL2 (chemokine ligand 2) antibody Carlumab, connected via the Mc-VC-PAB linker to the topoisomerase I inhibitor SN38. The toxic component and linker of the ADC is Mc-VC-PAB-SN38. This ADC is employed in cancer research studies.

Doxorubicin liposome is Doxorubicin hydrochloride encapsulated within liposomes. Doxorubicin, a cytotoxic anthracycline antibiotic, is a potent inhibitor of human DNA topoisomerase I and topoisomerase II. The liposomal encapsulation reduces the cardiac toxicity associated with Doxorubicin and extends its circulation time in the body, allowing for effective targeting of tumor tissue.

Doxorubicin hydrochloride (Standard) is a reference standard for research and analysis in studies involving Doxorubicin hydrochloride. Doxorubicin hydrochloride is an anthracycline antibiotic with cytotoxic and antitumor activity. It is an effective inhibitor of human DNA topoisomerase I and II, with IC50 values of 0.8 μM and 2.67 μM, respectively. In addition to inhibiting DNA topoisomerases, it can reduce the phosphorylation of AMPK and its downstream target, acetyl-CoA carboxylase. Doxorubicin hydrochloride also induces apoptosis and autophagy. In animal studies, it is commonly used to induce models of acute renal failure, chronic kidney injury, and heart failure.

Groenlandicine is a protoberberine alkaloid from Coptidis Rhizoma. Groenlandicine exhibits moderate inhibitory effect with IC50 value of 154.2 μM for human recombinant aldose reductase (HRAR). Groenlandicine selectively induces topoisomerase I-mediated DN

Eupolauridine is a selective DNA topoisomerase II inhibitor, exhibiting an IC50 of 20 μM against fungal topoisomerase I and 33 μM for human topoisomerase I. By inhibiting the catalytic activity of topoisomerase II, Eupolauridine stabilizes the enzyme's cleavage complex with DNA, resulting in DNA damage and imparting antifungal activity. [Eupolauridine] holds potential for the study of fungal infectious diseases.

Isodiospyrin is a novel human DNA topoisomerase I inhibitor, it exhibits cytotoxic activity to tumor cell lines. Isodiospyrin has antibacterial activity, the minimum inhibitory concentrations (MICs) against Gram-positive bacteria ranged from 0.78 to 50 mi