Topo I
Topo I regulates DNA topology by relaxing DNA supercoiling during transcription, DNA replication, and chromatin remodeling[1]. Mechanistically, TOP1 supports efficient RNA polymerase II transcription and limits transcription-replication conflicts that generate replication stress and genome instability[2][3][4]. In disease-relevant cancer research, Topo I inhibitors exploit this biology by trapping TOP1-DNA cleavage complexes, with camptothecins, irinotecan, and topotecan used as reference tools for anticancer studies[5][6]. Compared with related isoforms, human topoisomerases include TOP1 and mitochondrial TOP1MT as type IB enzymes, while TOP2A/TOP2B and TOP3A/TOP3B belong to distinct topoisomerase classes with different genome-maintenance roles[1][7].
References:
- [1]. Pommier Y, et al. Human topoisomerases and their roles in genome stability and organization. Nat Rev Mol Cell Biol. 2022 Jun;23(6):407-427. [Content Brief]
- [2]. Baranello L, et al. RNA Polymerase II Regulates Topoisomerase 1 Activity to Favor Efficient Transcription. Cell. 2016 Apr 7;165(2):357-71. [Content Brief]
- [3]. Tuduri S, et al. Topoisomerase I suppresses genomic instability by preventing interference between replication and transcription. Nat Cell Biol. 2009 Nov;11(11):1315-24. [Content Brief]
- [4]. Promonet A, et al. Topoisomerase 1 prevents replication stress at R-loop-enriched transcription termination sites. Nat Commun. 2020 Aug 7;11(1):3940. [Content Brief]
- [5]. Pommier Y. DNA topoisomerase I inhibitors: chemistry, et al. DNA topoisomerase I inhibitors: chemistry, biology, and interfacial inhibition. Chem Rev. 2009 Jul;109(7):2894-902. [Content Brief]
- [6]. Mathijssen RH, et al. Pharmacology of topoisomerase I inhibitors irinotecan (CPT-11) and topotecan. Curr Cancer Drug Targets. 2002 Jun;2(2):103-23. [Content Brief]
- [7]. Zhang H, et al. Human mitochondrial topoisomerase I. Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10608-13. [Content Brief]
-
Topo I Related Products (163)
Related Products (163)
-
Doxorubicin hydrochloride
0 ImagesSynonyms: Hydroxydaunorubicin hydrochloride; ADRDoxorubicin hydrochloride (Hydroxydaunorubicin hydrochloride; ADR), a cytotoxic anthracycline antibiotic, is an anti-cancer chemotherapy agent. Doxorubicin hydrochloride is a potent human DNA topoisomerase I and topoisomerase II inhibitor with IC50s of 0.8 μM and 2.67 μM, respectively. Doxorubicin hydrochloride reduces basal phosphorylation of AMPK and its downstream target acetyl-CoA carboxylase. Doxorubicin hydrochloride induces apoptosis and autophagy.
-
DXd
0 ImagesSynonyms: Exatecan derivative for ADCDXd (Exatecan derivative for ADC) is a potent DNA topoisomerase I inhibitor, with an IC50 of 0.31 μM, used as a conjugated drug of HER2-targeting ADC (DS-8201a).
-
SN-38
0 ImagesSynonyms: 7-Ethyl-10-hydroxycamptothecinSN-38 is an active metabolite of the Topoisomerase I inhibitor Irinotecan. SN-38 can bind to RPL15. SN-38 inhibits DNA and RNA synthesis with IC50s of 0.077 and 1.3 μM, respectively. SN-38 is a payload of sacituzumab govitecan (HY -132254).
-
Irinotecan
0 ImagesSynonyms: (+)-Irinotecan; CPT-11; VAL-413free baseIrinotecan ((+)-Irinotecan) is a topoisomerase I inhibitor, preventing religation of the DNA strand by binding to topoisomerase I-DNA complex.
-
Camptothecin
0 ImagesSynonyms: Campathecin; (S)-(+)-Camptothecin; CPTCamptothecin (CPT), a kind of alkaloid, is a DNA topoisomerase I (Topo I) inhibitor with an IC50 of 679 nM. Camptothecin (CPT) exhibits powerful antineoplastic activity against colorectal, breast, lung and ovarian cancers, modulates hypoxia-inducible factor-1α (HIF-1α) activity by changing microRNAs (miRNA) expression patterns in human cancer cells.
-
BL-B01D1
0 ImagesCat. No.: HY-164702Purity: 99.65%Synonyms: Izalontamab BrengitecanBL-B01D1 (Izalontamab Brengitecan) is a bispecific antibody-drug conjugate (ADC) targeting EGFR and HER3, formed by conjugating the EGFR/HER3 bispecific antibody Izalontamab (HY-P99676) to a novel TOP-I inhibitor payload Deruxtecan 2-hydroxypropanamide (HY-153891) via a cleavable linker (Mc-Gly-Gly-Phe-Gly). BL-B01D1 binds to EGFR and HER3 on the surface of tumor cells, mediates endocytosis and releases the payload, inhibits topoisomerase I, blocks DNA replication and RNA synthesis, and disrupts DNA structure. BL-B01D1 induces cell cycle S-phase arrest, apoptosis, antibody-dependent cell-mediated cytotoxicity, and tumor cell death. BL-B01D1 can be used for cancer research.
-
Puxitatug samrotecan
0 ImagesSynonyms: AZD 8205; P-SamPuxitatug samrotecan (AZD 8205) is an antibody-drug conjugate (ADC) targeting B7-H4, formed by the random conjugation of the Puxitatug (HY-P990059) antibody and AZ14170133 (HY-145399) via interchain cysteine reduction. Puxitatug samrotecan binds to B7-H4 to deliver the payload to B7-H4-expressing cells, inhibits topoisomerase I, and induces cytotoxicity in cancer cells and xenograft models. Puxitatug samrotecan can be used in studies of B7-H4-expressing tumors.
-
AZD0516
0 ImagesCat. No.: HY-173639Purity: 99.15%AZD0516 is an antibody-drug conjugate (ADC) targeting STEAP2. It is formed by conjugating an anti-STEAP2 monoclonal antibody (mAb) via interchain cysteines to a maleimide-reactive, β-glucuronidase-cleavable linker (HY-173635) and the topoisomerase 1 inhibitor Exatecan (HY-13631). AZD0516 is applicable to the research of metastatic castration-resistant prostate cancer.
-
Datopotamab deruxtecan (solution)
0 ImagesSynonyms: DS-1062 (solution); Dato-DXd (solution)Datopotamab deruxtecan (DS-1062) solution is a TROP2-targeted antibody-drug conjugate (ADC) with human TROP2 Kd of 0.74 nmol/L. Datopotamab deruxtecan solution consists of the antibody Datopotamab (HY-P99843) and the toxic molecule-linker conjugate Deruxtecan (HY-13631E). Datopotamab deruxtecan solution binds TROP2, triggers internalization and lysosomal trafficking and releases DXd topoisomerase I inhibitor payload. Datopotamab deruxtecan solution disrupts DNA function, induces DNA damage, apoptosis, and bystander killing of tumor microenvironment cells. Datopotamab deruxtecan solution can be used in research related to triple-negative breast cancer, gastric cancer, and non-small cell lung cancer.
-
Topotecan hydrochloride
0 ImagesSynonyms: SKF 104864A hydrochloride; NSC 609669 hydrochlorideTopotecan Hydrochloride (SKF 104864A Hydrochloride) is a Topoisomerase I inhibitor with potent antineoplastic activities.
-
Irinotecan hydrochloride
0 ImagesSynonyms: (+)-Irinotecan hydrochloride; CPT-11 hydrochloride; VAL-413Irinotecan hydrochloride ((+)-Irinotecan hydrochloride) is a topoisomerase I inhibitor mainly used to treat colon cancer and rectal cancer.
-
Ifinatamab deruxtecan
0 ImagesSynonyms: DS-7300a; MABX-9001a; I-DXdIfinatamab deruxtecan (DS-7300a) is a B7-H3-targeting Antibody-drug conjugate (ADC), which is composed of a humanized anti-B7-H3 monoclonal antibody, an enzymatically cleavable peptide-based linker, and Exatecan derivative (DXd) (HY-13631D). Ifinatamab deruxtecan is a DNA Topoisomerase I inhibitor. Ifinatamab deruxtecan induces Apoptosis. DS-7300a exerts potent antitumor activities against B7-H3-expressing tumors. against rhabdomyosarcoma, endometrial adenocarcinoma and lung adenocarcinoma. Ifinatamab deruxtecan does not exert direct immunomodulatory effects
-
Betulinic acid
0 ImagesBetulinic acid is a natural pentacyclic triterpenoid, acts as a eukaryotic topoisomerase I inhibitor, with an IC50 of 5 μM, and possesses anti-HIV, anti-malarial, anti-inflammatory and anti-tumor properties. Betulinic acid can cross the blood-brain barrier.
-
β-Lapachone
0 Imagesβ-Lapachone (ARQ-501;NSC-26326) is a naturally occurring O-naphthoquinone, acts as a topoisomerase I inhibitor, and induces apoptosis by inhibiting cell cycle progression.
-
DXd-d5
0 ImagesCat. No.: HY-13631DSPurity: 99.57%Synonyms: Exatecan-d5 derivative for ADCDXd-d5 is a deuterium labeled DXd. DXd is a potent DNA topoisomerase I inhibitor, with an IC50 of 0.31 μM, used as a conjugated drug of HER2-targeting ADC (DS-8201a) .
-
Telisotuzumab Adizutecan
0 ImagesSynonyms: ABBV-400; Temab-ATelisotuzumab Adizutecan (ABBV-400) is an anti-c-Met antibody-drug conjugate (ADC). Telisotuzumab Adizutecan is composed of the humanized anti-c-Met antibody Telisotuzumab (HY-P99391) and the topoisomerase 1 inhibitor (7-MAD-MDCPT) (HY-132162). Telisotuzumab Adizutecan exhibits significant anti-tumor activity against advanced solid tumors such as colorectal cancer, gastric cancer, and non-small cell lung cancer.
-
PNU-159682
0 ImagesPNU-159682, a metabolite of the anthracycline Nemorubicin, is a highly potent DNA topoisomerase II inhibitor with excellent cytotoxicity. PNU-159682 acts as a more potent and tolerated ADC cytotoxin than Doxorubicin for ADC synthesis. PNU-159682 can be used in EDV-nanocell technology to overcome agent resistance.
-
Irinotecan hydrochloride trihydrate
0 ImagesSynonyms: (+)-Irinotecan hydrochloride trihydrate; CPT-11 hydrochloride trihydrateIrinotecan hydrochloride trihydrate ((+)-Irinotecan hydrochloride trihydrate) is a topoisomerase I inhibitor with antitumor activity.
-
Aclacinomycin A
0 ImagesCat. No.: HY-N2306CAS No.: 57576-44-0Synonyms: AclarubicinAclacinomycin A (Aclarubicin) is an orally active and potent anthracycline antitumor antibiotic. Aclacinomycin A is an inhibitor of topoisomerase I and II. Aclacinomycin A inhibits synthesis of nucleic acid, especially RNA. Aclacinomycin A might inhibit the 26S protease complex as well as the ubiquitin-ATP-dependent proteolysis.
-
Precemtabart tocentecan
0 ImagesSynonyms: Precem-TcT; M 9140Precemtabart tocentecan (Precem-TcT; M 9140) is an anti-CEACAM5 (carcinoembryonic antigen-related cell adhesion molecule 5) antibody-drug conjugate (ADC). Precemtabart tocentecan consists of a tumor-specific anti-CEACAM5 monoclonal antibody Precemtabart (HY-P990940), a highly hydrophilic and stable cleavable β-glucuronide linker, and a topoisomerase 1 inhibitor payload Exatecan (HY-13631), and the drug-linker conjugate for ADC is Mal-Gly-PAB-Exatecan-D-glucuronic acid (HY-153179). Precemtabart tocentecan inhibits the growth of CEACAM5-positive cancer cells. Precemtabart tocentecan exhibits significant antitumor activity in CEACAM5-expressing xenograft models. Precemtabart tocentecan can be used for the study of CEACAM5-expressing advanced solid tumors, especially mCRC.
