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]
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Topo I Related Products (158)
Related Products (158)
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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.
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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).
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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).
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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.
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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.
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Mocertatug rezetecan (DAR6)
0 ImagesCat. No.: HY-185280CAS No.: 3042848-25-6Synonyms: HS-20089 (DAR6); GSK5733584 (DAR6)Mocertatug rezetecan (DAR6) (HS-20089 (DAR6); GSK5733584 (DAR6)) is an antibody-drug conjugate (ADC) targeting B7-H4, composed of Mocertatug (HY-P991703) and MC-Gly-Gly-Phe-Gly-(R)-Cyclopropane-Exatecan (HY-148668). Mocertatug rezetecan (DAR6) delivers a TOPO1 inhibitor payload. It binds to B7-H4-expressing tumor cells, triggers ADC internalization, and induces S-phase cell cycle arrest, cytotoxicity, and bystander killing effect. Mocertatug rezetecan (DAR6) exhibits dose-dependent tumor growth inhibition in breast cancer and endometrial cancer CDX models. It can be used in research related to platinum-resistant ovarian cancer, breast cancer, endometrial cancer, cholangiocarcinoma, and cervical cancer.
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Datopotamab deruxtecan
0 ImagesSynonyms: DS-1062; Dato-DXdDatopotamab deruxtecan (DS-1062) is a TROP2-targeted antibody-drug conjugate (ADC) with human TROP2 Kd of 0.74 nmol/L. Datopotamab deruxtecan consists of the antibody Datopotamab (HY-P99843) and the toxic molecule-linker conjugate Deruxtecan (HY-13631E). Datopotamab deruxtecan binds TROP2, triggers internalization and lysosomal trafficking and releases DXd topoisomerase I inhibitor payload. Datopotamab deruxtecan disrupts DNA function, induces DNA damage, apoptosis, and bystander killing of tumor microenvironment cells. Datopotamab deruxtecan can be used in research related to triple-negative breast cancer, gastric cancer, and non-small cell lung cancer.
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SN-38-A2
0 ImagesCat. No.: HY-184984CAS No.: 3110372-70-5SN-38-A2 is a topoisomerase I (TOP1) degrader with an IC50 of 6.2 nM in MIA PaCa-2 pancreatic cancer cells. SN-38-A2 mimics protein misfolding via an adamantane hydrophobic tag, hijacks the HSP90 chaperone system, and mediates TOP1 degradation through the ubiquitin-proteasome system. SN-38-A2 assembles with poly β-cyclodextrin to form pH-responsive nanoparticles, enabling site-specific release under the acidic conditions of the tumor microenvironment, and exhibits tumor growth inhibitory effects in MIA PaCa-2 pancreatic cancer and HCT116 colorectal cancer xenograft models. SN-38-A2 can be used in research related to pancreatic cancer, colorectal cancer, and breast cancer.
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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.
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Topotecan hydrochloride
0 ImagesSynonyms: SKF 104864A hydrochloride; NSC 609669 hydrochlorideTopotecan Hydrochloride (SKF 104864A Hydrochloride) is a Topoisomerase I inhibitor with potent antineoplastic activities.
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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.
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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
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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.
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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.
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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) .
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Telisotuzumab Adizutecan
0 ImagesCat. No.: HY-171945CAS No.: 2850366-99-1Synonyms: 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.
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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.
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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.
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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.
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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.
