dna topoisomerasei

DRF-1042, an orally active camptothecin analog, exhibits anticancer and insecticidal activities by inhibiting DNA topoisomerase I. It has been studied for its efficacy against solid tumors, including prostate and colon cancers.

Camptothecin (CPT) belongs to the alkaloid group of natural products and is a specific DNA topoisomerase I (Topo I) inhibitor (IC50=679 nM) with specificity. Camptothecin has antitumor activity and induces apoptosis.

CL2A-SN-38 consists of a CL2A linker and an anticancer compound, SN-38, which delivers active molecules within tumor cells and in the tumor microenvironment, often in conjunction with antibodies to make biologically active antibody-coupled reactive molecules (ADCs).

Phenoxodiol (Idronoxil) activates the mitochondrial caspase system, inhibits X-linked inhibitor of apoptosis(XIAP), disrupts FLICE inhibitory protein(FLIP) expression, and sensitizes the cancer cells to Fas-mediated apoptosis. Phenoxodiol induces cell cycle arrest in the G1/S phase of the cell cycle and upregulates p21WAF1 via a p53 independent manner. Phenoxodiol also inhibits DNA topoisomerase II.

DNA topoisomerase II inhibitor 1 is a potent inhibitor of DNA topoisomerase II that arrests the cell cycle in sub-G1 phase and induces apoptosis with anti-value-added effects.

DBCO-PEG3-VC-Exatecan (compound 25) is a Drug-Linker Conjugate for ADC (ADC Drug-Linker Conjugate), consisting of the ADC linker (DBCO-PEG3-VC) coupled with the DNA topoisomerase I (topoisomeraseI) inhibitor Exatecan. This conjugate is utilized in the development of antibody-drug conjugates for targeted cancer therapy.

TopoisomeraseI inhibitor 17 (Compound 7h) is an inhibitor of TopoisomeraseI (Top1). It reduces DDX5 and reverses the locking effect of DDX5 on Top1 activity. This compound induces Top1-mediated DNA damage and promotes reactive oxygen species (ROS) production. It triggers apoptosis by decreasing anti-apoptotic proteins XIAP, Bcl-2, and Survivin, while increasing pro-apoptotic proteins Bax and γH2AX. Moreover, TopoisomeraseI inhibitor 17 halts progression at the G2/M checkpoint, leading to cell cycle arrest. It significantly impairs colorectal cancer cell colony formation and migration, and effectively reduces tumor size in human PDX tumor mouse models.

TopoisomeraseI/II inhibitor 8 (Compound Ru7) is a dual catalytic inhibitor of TopoisomeraseI/II that induces DNA damage and activates PARP-1, leading to the activation of RIPK1, RIPK3, and MLKL, ultimately causing necroptosis. It shows significant anticancer activity by effectively targeting cancer cell nuclei and inducing cell death through necroptosis, offering substantial clinical potential in overcoming resistance in cancer treatment.

Mal-Exatecan (Mal-DX-8951) is a malonamide (Mal)-modified antibody-drug conjugate used for preparing ADCs (antibody-drug conjugates) and studying cancer. Exatecan is an effective topoisomerase I inhibitor

Exatecanintermediate 11 is an intermediate compound used in the synthesis of Exatecan. Exatecan (DX-8951) is a frequently utilized cytotoxic component in the preparation of antibody-drug conjugates (ADC Cytotoxin) and serves as an inhibitor of DNA topoisomerase I (topoisomeraseI) with an IC50 of 2.2 μM.

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.

Gly-Cyclopropane-Exatecan, a DNA Topoisomerase I inhibitor containing Exatecan, is key in synthesizing the anti-B7-H4 ADC, specifically the ADC hu2F7-Exatecan (compound 34). This compound demonstrated antitumor activity both in vivo and in vitro [1].

(1R,9R)-Exatecan mesylate ((1R,9R)-DX8951f) is an isomer of Exatecan mesylate, an inhibitor of DNA topoisomerase I with an IC50 of 2.2 μM (0.975 μg/mL), and useful in cancer research [1].

SN-38-d3 is a deuterated form of SN-38. As the active metabolite of the topoisomerase I (TopoisomeraseI) inhibitor irinotecan, SN-38 (NK012) notably inhibits the synthesis of DNA and RNA, with IC50 values of 0.077 and 1.3 μM, respectively.