Camptothecins
Camptothecins act through DNA topoisomerase I (Top1), an enzyme essential for DNA replication and transcription[1][2]. Mechanistically, camptothecin, topotecan, and irinotecan stabilize Top1-DNA cleavable complexes, block DNA resealing, and generate replication-associated DNA double-strand breaks[3][4]. This Top1-focused mechanism distinguishes camptothecins from Top2 inhibitors, which can induce DNA damage in both replicating and non-replicating cells[3]. In intact cells, topotecan-induced Top1-DNA covalent complexes can be detected by immunoblotting, immunofluorescence, or flow cytometry, supporting mechanism-based pharmacodynamic analysis[5]. In cancer models, ATR inhibition sensitizes cells to camptothecin-class Top1 inhibitors by disabling DNA replication initiation and fork elongation responses[6]. Camptothecin derivatives also poison Leishmania DNA topoisomerase IB and reduce parasitic burden in infected splenocytes[7]. For colorectal cancer research, SN-38 suppresses Nrf2 transcriptional activity and can enhance sensitivity to Nrf2-sensitive anticancer drugs[8].
References:
- [1]. Wang W, et al. The optimal choice for pancreatic anastomosis after pancreaticoduodenectomy: A network meta-analysis of randomized control trials. Int J Surg. 2018 Sep;57:111-116. [Content Brief]
- [2]. Jain CK, et al. Natural Compounds as Anticancer Agents Targeting DNA Topoisomerases. Curr Genomics. 2017 Feb;18(1):75-92. [Content Brief]
- [3]. Zhao H, et al. Relationship of DNA Damage Signaling to DNA Replication Following Treatment with DNA Topoisomerase Inhibitors Camptothecin/Topotecan, Mitoxantrone, or Etoposide. Cytometry A. 2011 Dec 2;79A:21172. [Content Brief]
- [4]. Yakkala PA, et al. Prospects of Topoisomerase Inhibitors as Promising Anti-Cancer Agents. Pharmaceuticals (Basel). 2023 Oct 13;16(10):1456. [Content Brief]
- [5]. Patel AG, et al. Immunodetection of human topoisomerase I-DNA covalent complexes. Nucleic Acids Res. 2016 Apr 7;44(6):2816-26. [Content Brief]
- [6]. Jossé R, et al. ATR inhibitors VE-821 and VX-970 sensitize cancer cells to topoisomerase i inhibitors by disabling DNA replication initiation and fork elongation responses. Cancer Res. 2014 Dec 1;74(23):6968-79. [Content Brief]
- [7]. Prada CF, et al. Gimatecan and other camptothecin derivatives poison Leishmania DNA-topoisomerase IB leading to a strong leishmanicidal effect. Biochem Pharmacol. 2013 May 15;85(10):1433-40. [Content Brief]
- [8]. Wang J, et al. SN-38, an active metabolite of irinotecan, inhibits transcription of nuclear factor erythroid 2-related factor 2 and enhances drug sensitivity of colorectal cancer cells. Mol Carcinog. 2024 Apr;63(4):742-756. [Content Brief]
-
Camptothecins Related Products (33)
Related Products (33)
- 1
- 2
-
Deruxtecan
0 ImagesSynonyms: MC-GGFG-DXDDeruxtecan is an ADC drug-linker conjugate composed of an DX-8951 derivative (DXd) and a maleimide-GGFG peptide linker, used for synthesizing Trastuzumab deruxtecan (HY-138298A) and Patritumab deruxtecan (HY-P99813).
-
CL2A-SN-38
0 ImagesCL2A-SN-38 is a agent-linker conjugate composed of a potent a DNA Topoisomerase I inhibitor SN-38 and a linker CL2A to make antibody agent conjugate (ADC). CL2A-SN-38 provides significant and specific antitumor effects against a range of human solid tumor types. CL2A-SN-38 uses hydrolyzable linker to deliver active agents within tumor cells and in the tumor microenvironment, resulting in bystander effects.
-
Mal-Gly-PAB-Exatecan-D-glucuronic acid
0 ImagesMal-Gly-PAB-Exatecan-D-glucuronic acid can be used for Antibody-Drug Conjugates (ADCs) synthesis. Mal-Gly-PAB-Exatecan-D-glucuronic acid can be used for research of tumor research and diagnosis.
-
MC-GGFG-Exatecan
0 ImagesCat. No.: HY-114233CAS No.: 1600418-29-8Synonyms: MC-GGFG-DX8951MC-GGFG-Exatecan (MC-GGFG-DX8951) is a agent-linker conjugate for ADC. MC-GGFG-Exatecan is a DX8951 (a DNA topoisomerase I inhibitor) derivative with protease cleavable MC-GGFG linker. MC-GGFG-Exatecan shows antitumor activity and can be used to prepare DX8951 antibody conjugate (ADC).
-
MC-Val-Cit-PAB-Exatecan
0 ImagesSynonyms: MC-Val-Cit-PAB-DX8951MC-Val-Cit-PAB-Exatecan (MC-Val-Cit-PAB-DX8951) is a agent-linker conjugate for ADC. MC-Val-Cit-PAB-Exatecan is composed of a DNA topoisomerase I DX-8951 (HY-13631) and a cathepsin cleavable ADC linker.
-
MC-VA-PAB-Exatecan
0 ImagesMC-VA-PAB-Exatecan is a agent-linker conjugate for ADC. MC-VA-PAB-Exatecan contains the ADC linker (peptide MC-VA-PAB) and a DNA topoisomerase I inhibitor Exatecan (HY-13631). MC-VA-PAB-Exatecan synthesized ADC shows good antitumor activity.
-
AZ14170133
0 ImagesSynonyms: SG 3932; AZ-0133AZ14170133 (SG 3932; AZ-0133) is a Drug-Linker Conjugates for ADC. AZ14170133 consists of the ADC cytotoxic payload topoisomerase 1 inhibitor and a linker. AZ14170133 can be used for synthesis of ADC AZD9592 (HY-171124) and AZD 8205 (HY-171689). AZ14170133 can be used for the research of cancer.
-
MC-Gly-Gly-Phe-Gly-(R)-Cyclopropane-Exatecan
0 ImagesCat. No.: HY-148668CAS No.: 2414254-51-4Synonyms: SHR-A1811 Drug-linkerMC-Gly-Gly-Phe-Gly-(R)-Cyclopropane-Exatecan (SHR-A1811 Drug-linker) is a agent-linker conjugates for ADC, consisting Exatecan (HY-13631). Exatecan is a DNA Topoisomerase I inhibitor (IC50=2.2 μM).
-
DBCO-PEG3-VC-Exatecan
0 ImagesDBCO-PEG3-VC-Exatecan (compound 25) is a Drug-Linker Conjugate for ADC. DBCO-PEG3-VC-Exatecan contains the ADC linker (DBCO-PEG3-VC) and a DNA topoisomerase I inhibitor Exatecan (HY-13631).
-
Val-Ala-PABC-Exatecan
0 ImagesVal-Ala-PABC-Exatecan is a Drug-Linker Conjugates for ADC, consiting of a cleavable Tesirine linker (Val-Ala-PABC) and Exatecan (HY-13631) (topoisomerase I inhibitor). Val-Ala-PABC-Exatecan can be used for ADC molecues synthesis, such as Mal-PEGn-amide-va-Exatecan.
-
Gly-Gly-Phe-Gly-NH-O-CO-Exatecan hydrochloride
0 ImagesGly-Gly-Phe-Gly-NH-O-CO-Exatecan, as a drug-linker conjugate composed of linker Gly-Gly-Phe-Gly-NH-O-CO and Exatecan, can be used to prepare antibody conjugate drugs. Exatecan is a DNA topoisomerase I inhibitor that can be used in cancer research.
-
Val-Cit-PAB-Exatecan
0 ImagesCat. No.: HY-153031CAS No.: 2227350-99-2Synonyms: Val-Cit-PAB-DX8951Val-Cit-PAB-Exatecan (Val-Cit-PAB-DX8951) is a agent-linker conjugate for ADC. Val-Cit-PAB-Exatecan is composed of a DNA topoisomerase I DX-8951 (HY-13631) and a cathepsin cleavable ADC linker.
-
MAC glucuronide phenol-linked SN-38
0 ImagesMAC glucuronide phenol-linked SN-38 is a pH-susceptible lactone MAC glucuronide phenol-linked SN-38 (DNA topoisomerase I inhibitor) agent linker. MAC glucuronide phenol-linked SN-38 is cytotoxic across L540cy cells and Ramos cells with IC50 values of 113 and 67 ng/mL, respectively.Albumin-coupled MAC glucosidol-linked SN-38 shows good stability in mouse plasma.
-
2-MSP-5-HA-GGFG-NH-CH2-O-CH2-CO-Exatecan
0 Images2-MSP-5-HA-GGFG-NH-CH2-O-CH2-CO-Exatecan is a drug-linker conjugates for ADC, consiting of a cleavable linker and Exatecan (HY-13631). 2-MSP-5-HA-GGFG-NH-CH2-O-CH2-CO-Exatecan can be linked to anti-Her3 antibody.
-
DBCO-β-Glu-PEG12-Exatecan
0 ImagesDBCO-β-Glu-PEG12-Exatecan (Compound 107) is an inhibitor for topoisomerase I. DBCO-β-Glu-PEG12-Exatecan can be used as a Drug-Linker Conjugate for ADC molecule.
-
DBM-GGFG-NH-O-CO-Exatecan
0 ImagesCat. No.: HY-160807CAS No.: 2769152-95-4DBM-GGFG-NH-O-CO-Exatecan (Example 4, Compound 14) is a conjugate of an ADC drug toxin molecule and a linker. DBM-GGFG-NH-O-CO-Exatecan is a complete antibody-drug conjugate intermediate that integrates a potent camptothecin-based toxin, a cleavable peptide linker (GGFG), and a reactive terminus that can directly conjugate to antibodies.
-
Mal-PEG8-Phe-Lys-PAB-Exatecan TFA
0 ImagesCat. No.: HY-148380APurity: 98.66%
- 1
- 2
