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Chemical Structure| 97682-44-5 Chemical Structure| 97682-44-5

Structure of Irinotecan
CAS No.: 97682-44-5

Chemical Structure| 97682-44-5

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Irinotecan is a topoisomerase I inhibitor used in the study of colon and rectal cancers.

Synonyms: CPT-11; VAL-413(free base); (+)-Irinotecan

4.5 *For Research Use Only !

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Huang, Chengyi ; Lan, Huiyin ; Bai, Minghua ; Chen, Jinggang ; Xu, Shengkun ; Sun, Quanquan , et al.

Abstract: Background: Irinotecan is a chemotherapeutic drug widely used to treat solid tumors. However, its effectiveness is limited by the severely delayed onset of diarrhea. This study aimed to confirm the protective effects of the non-systemic oral antibiotic rifaximin on irinotecan-induced mucositis in mice model. Materials and methods: Six to eight week-old BALB/c mice were treated with saline, irinotecan (50 mg/kg, i.p. once daily), rifaximin (50 mg/kg, p.o. twice daily), or irinotecan + rifaximin for 9 consecutive days. Signs of diarrhea, bloody diarrhea, and body weight were monitored daily. Intestinal tissues were harvested for histopathological analysis and quantitative PCR. SN38 and SN38G concentration in intestine were detected using lC-MS analysis. Intestinal bacteria β-glucuronidase (BGUs) activity was detected using mouse feces. We performed 16S rRNA sequencing to investigate the gut microbiota composition. Gut permeability was tested in vivo by measuring the fluorescein isothiocyanate-dextran intensity in the serum. Results: Rifaximin reduced the frequency of delayed diarrhea and attenuated the severity of diarrhea caused by irinotecan in mice. Rifaximin significantly inhibited SN38 exposure in intestine and irinotecan-induced increase in BGUs activity. Rifaximin alleviated intestinal mucosal inflammation, prevented intestinal epithelial damage caused by irinotecan, and maintained gut barrier function. Moreover, the consecutive use of rifaximin did not cause a disorder in gut microbiota and reduced irinotecan-induced Firmicutes expansion. More importantly, rifaximin inhibited the expansion of some microbiota (such as Blautia, Eggerthella, and f_enterobacteriaceae) and promoted an increase in beneficial microbiota (such as Lactobacillus intestinalis, Lachnospiraceae NK4A136 group, and f_Oscillospiraceae). Conclusions: Preventive use of rifaximin is a feasible method to protect against irinotecan-induced diarrhea.

Keywords: Rifaximin ; irinotecan ; diarrhea ; gut microbiota

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Cheng, Dongfeng ; Fan, Juanjuan ; Qin, Kai ; Zhou, Yiran ; Yang, Jingrui ; Ma, Yang , et al.

Abstract: Pancreatic cancer (PC) is one of the deadliest gastrointestinal cancers, accounting for the fourth highest number of cancer-related fatalities. Increasing data suggests that mesenchymal stem cells (MSCs) might influence the drug resistance of GC cells in the tumor microenvironment and play essential roles in drug resistance development. However, the precise underlying process remains a mystery. The purpose of this study was to look at the control of MSC-induced SNHG7 in pancreatic cancer. In vitro and in vivo sphere formation, colony formation, and flow cytometry investigations revealed the stemness and Folfirinox resistance in pancreatic cancer cells. To confirm the direct connections between SNHG7 and other related targets, RNA pulldown and immunoprecipitation tests were performed. MSC co-culture enhanced the stemness and Folfirinox resistance in pancreatic cancer cells according to the findings. MSC coculture increased SNHG7 expression in pancreatic cancer cells, contributing to the stemness and Folfirinox resistance. We demonstrated that Notch1 interacted with SNHG7 and could reverse the facilitative effect of SNHG7 on the stemness and Folfirinox resistance in pancreatic cancer cells. Finally, our findings showed that MSCs increased SNHG7 expression in pancreatic cancer cells, promoting the stemness and Folfirinox resistance via the Notch1/Jagged1/Hes-1 signaling pathway. These findings could provide a novel approach and therapeutic target for pancreatic cancer patients.

Keywords: SNHG7 ; Notch1 ; pancreatic cancer ; stemness ; resistance

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Alternative Products

Product Details of Irinotecan

CAS No. :97682-44-5
Formula : C33H38N4O6
M.W : 586.68
SMILES Code : O=C(N1CCC(N2CCCCC2)CC1)OC3=CC=C4N=C5C(CN6C(C(COC([C@@]7(CC)O)=O)=C7C=C65)=O)=C(CC)C4=C3
Synonyms :
CPT-11; VAL-413(free base); (+)-Irinotecan
MDL No. :MFCD00866307

Safety of Irinotecan

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H301
Precautionary Statements:P501-P270-P264-P301+P310+P330-P405
Class:6.1
UN#:1544
Packing Group:

Related Pathways of Irinotecan

DNA

Isoform Comparison

Biological Activity

Description
Irinotecan ((+)-Irinotecan) is a topoisomerase I inhibitor by preventing the DNA strand's religation through its binding to the topoisomerase I-DNA complex[1].

In Vitro:

Cell Line
Concentration Treated Time Description References
RKO cells 2.5 µM 96 hours Induce cellular senescence and evaluate changes in cell proliferation, migration, and invasion abilities Mol Cancer. 2024 Apr 4;23(1):70
HCT116 cells 1.5 µM 96 hours Induce cellular senescence and evaluate changes in cell proliferation, migration, and invasion abilities Mol Cancer. 2024 Apr 4;23(1):70
Pancreatic ductal adenocarcinoma PDX tumor tissue slices 10 μM, 30 μM 72 h Test the sensitivity of PDX tumor tissue slices to irinotecan, results were consistent with patients' clinical responses. Clin Cancer Res. 2016 Dec 15;22(24):6021-6030.
HT29 cells 3.125 to 100 µM 24 h Irinotecan (CPT-11) as the positive control significantly inhibited the proliferation of HT29 cells, with a GI50 of 5.19 µM. Biomolecules. 2019 Aug 27;9(9):418.
HT29-dx cells 1 µM 24 h The anti-tumor effect of irinotecan on chemotherapy-resistant HT29-dx cells was studied. The results showed that irinotecan could reduce the IC50 value of drug-resistant cells and restore its anti-tumor effect Mol Cancer. 2013 Nov 13;12:137.
HT-29 human colorectal cancer cells 20 µM 1.5 h To investigate the effects of irinotecan alone or in combination with 5-FU on the growth, metabolic activity, and proliferation of HT-29 cells. The results showed that irinotecan alone or in combination with 5-FU significantly inhibited the growth, metabolic activity, and proliferation of HT-29 cells. Int J Mol Sci. 2023 Jun 20;24(12):10385.
TFK-1 cells 20 µg/ml 72 h Irinotecan treatment significantly reduced cell viability, increased cytotoxicity, and induced the expression of inflammation-related genes in TFK-1 cells. Sci Rep. 2019 Mar 13;9(1):4338.
EGI-1 cells 20 µg/ml 72 h Irinotecan treatment significantly reduced cell viability, increased cytotoxicity, and induced the expression of inflammation-related genes in EGI-1 cells. Sci Rep. 2019 Mar 13;9(1):4338.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Nude mice Pancreatic ductal adenocarcinoma PDX model Not specified 50 mg/kg Weekly for 3 weeks Validate LTSA results, irinotecan significantly inhibited tumor growth. Clin Cancer Res. 2016 Dec 15;22(24):6021-6030.
Mice Orthotopic colon cancer model Intravenous injection 40 mg/kg Every third or fourth day To evaluate the pharmacokinetics and tumor drug content of Ir-silicasome in a colon cancer model ACS Nano. 2019 Jan 22;13(1):38-53
Mice B16-Luc brain tumour model Intravenous injection 50 μM/kg Daily injection for 6 days Irinotecan suppressed subcutaneous tumour growth but minimally suppressed brain tumour growth. Br J Cancer. 2020 Nov;123(11):1633-1643
BALB/c nude mice Subcutaneous xenograft model Intraperitoneal injection 5 mg/kg Twice a week for approximately 50 days To study the role of eIF3a in irinotecan sensitivity in vivo, it was found that eIF3a downregulation increased resistance to irinotecan. Cell Prolif. 2022 Apr;55(4):e13208
Mice FLC PDX models Intraperitoneal injection 5 mg/kg Irinotecan: 5 days a week for 2 weeks; DT2216: Once or twice a week for 3 weeks To evaluate the synergistic effect of Irinotecan and DT2216 in FLC PDX models, results showed that Irinotecan and DT2216 have remarkable synergy in vivo at clinically achievable doses not associated with significant thrombocytopenia JCI Insight. 2022 Sep 8;7(17):e161820

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT00005626 Leukemia|Lymphoma PHASE2 COMPLETED 2025-11-03 H. Lee Moffitt Cancer Center a... More >>nd Research Institute, Tampa, Florida, 33612, United States Less <<
NCT02662959 Stomach Neoplasms PHASE2 UNKNOWN - Shanghai Cancer Center, Shangh... More >>ai, Shanghai, China Less <<
NCT05391126 Colorectal Cancer|Pancreatic C... More >>ancer Less << RECRUITING 2025-05-27 University of Kentucky, Lexing... More >>ton, Kentucky, 40506, United States Less <<
NCT00320320 Colorectal Neoplasms|Metastase... More >>s Less << PHASE2 TERMINATED 2025-04-07 Gachon University Gil Medical ... More >>Center, Incheon, 405 760, Korea, Republic of Less <<
NCT00509860 Sarcoma PHASE2 COMPLETED 2025-01-12 UT MD Anderson Cancer Center, ... More >>Houston, Texas, 77030, United States Less <<
NCT00072852 Breast Neoplasms PHASE2 COMPLETED 2025-05-07 Pfizer Investigational Site, M... More >>obile, Alabama, 36608, United States|Pfizer Investigational Site, Anchorage, Alaska, 99508, United States|Pfizer Investigational Site, Lewistown, Idaho, 83501, United States|Pfizer Investigational Site, Alton, Illinois, 62002, United States|Pfizer Investigational Site, Indianapolis, Indiana, 46227, United States|Pfizer Investigational Site, Overland Park, Kansas, 66210, United States|Pfizer Investigational Site, Chalmette, Louisiana, 70043, United States|Pfizer Investigational Site, Covington, Louisiana, 70433, United States|Pfizer Investigational Site, Mandeville, Louisiana, 70448, United States|Pfizer Investigational Site, Metairie, Louisiana, 70002, United States|Pfizer Investigational Site, Metairie, Louisiana, 70006, United States|Pfizer Investigational Site, New Orleans, Louisiana, 70115, United States|Pfizer Investigational Site, Boston, Massachusetts, 02114, United States|Pfizer Investigational Site, Boston, Massachusetts, 02115, United States|Pfizer Investigational Site, Boston, Massachusetts, 02130, United States|Pfizer Investigational Site, Detroit, Michigan, 48201, United States|Pfizer Investigational Site, Southaven, Mississippi, 38671, United States|Pfizer Investigational Site, Kansas City, Missouri, 64111, United States|Pfizer Investigational Site, St. Louis, Missouri, 63136, United States|Pfizer Investigational Site, St. Louis, Missouri, 63141, United States|Pfizer Investigational Site, Washington, Missouri, 63090, United States|Pfizer Investigational Site, New Brunswick, New Jersey, 08901-2601, United States|Pfizer Investigational Site, New Brunswick, New Jersey, 08903, United States|Pfizer Investigational Site, New York, New York, 10021, United States|Pfizer Investigational Site, Stony Brook, New York, 11794, United States|Pfizer Investigational Site, Kettering, Ohio, 45409, United States|Pfizer Investigational Site, Oklahoma City, Oklahoma, 73120, United States|Pfizer Investigational Site, Greenville, South Carolina, 29615, United States|Pfizer Investigational Site, Covington, Tennessee, 38019, United States|Pfizer Investigational Site, Franklin, Tennessee, 37067, United States|Pfizer Investigational Site, Gallatin, Tennessee, 37066, United States|Pfizer Investigational Site, Hermitage, Tennessee, 37076, United States|Pfizer Investigational Site, Lebanon, Tennessee, 37087, United States|Pfizer Investigational Site, Memphis, Tennessee, 38120, United States|Pfizer Investigational Site, Murfreesboro, Tennessee, 37130, United States|Pfizer Investigational Site, Nashville, Tennessee, 37203, United States|Pfizer Investigational Site, Nashville, Tennessee, 37205, United States|Pfizer Investigational Site, Nashville, Tennessee, 37207, United States|Pfizer Investigational Site, Nashville, Tennessee, 37211, United States|Pfizer Investigational Site, Dallas, Texas, 75204, United States|Pfizer Investigational Site, Dallas, Texas, 75230-2510, United States|Pfizer Investigational Site, Dallas, Texas, 75231, United States|Pfizer Investigational Site, Dallas, Texas, 75246, United States|Pfizer Investigational Site, Fort Worth, Texas, 76104, United States|Pfizer Investigational Site, Plano, Texas, 75075-7787, United States|Pfizer Investigational Site, Tyler, Texas, 75702, United States|Pfizer Investigational Site, Federal Way, Washington, 98003, United States|Pfizer Investigational Site, Lakewood, Washington, 98499, United States|Pfizer Investigational Site, Seattle, Washington, 98104-2499, United States|Pfizer Investigational Site, Seattle, Washington, 98104, United States|Pfizer Investigational Site, Seattle, Washington, 98109-1023, United States|Pfizer Investigational Site, Seattle, Washington, 98122, United States|Pfizer Investigational Site, Seattle, Washington, 98195, United States|Pfizer Investigational Site, Tacoma, Washington, 98405, United States|Pfizer Investigational Site, Vancouver, Washington, 98684, United States|Pfizer Investigational Site, Yakima, Washington, 98902, United States|Pfizer Investigational Site, Milwaukee, Wisconsin, 53215, United States|Pfizer Investigational Site, Capital Federal, Buenos Aires, 1426, Argentina|Pfizer Investigational Site, Rosario, Santa Fe, 2000, Argentina|Pfizer Investigational Site, Capital Federal, 1406, Argentina|Pfizer Investigational Site, Cordoba, 5000, Argentina|Pfizer Investigational Site, Santa Fe, 3000, Argentina|Pfizer Investigational Site, South Brisbane, Queensland, 4101, Australia|Pfizer Investigational Site, Frankston, Victoria, 3199, Australia|Pfizer Investigational Site, Bogota, Bogota DC, 464, Colombia|Pfizer Investigational Site, Wellington, 489, New Zealand Less <<
NCT01654081 Lung Cancer PHASE2 WITHDRAWN 2025-05-14 -
NCT00144378 Stomach Neoplasm|Neoplasm Meta... More >>stasis Less << PHASE3 COMPLETED - Charité,Universit?tsmedizin Be... More >>rlin, Campus Virchow Klinikum, Dep. orf Hematology and Oncology,, Berlin, Germany Less <<
NCT01826396 Colonic Neoplasms PHASE2 UNKNOWN 2025-12-14 Colorectal Cancer Institute of... More >> the Heilongjiang Academy of Medical Sciences, Harbin, Heilongjiang, 150001, China Less <<
NCT01635400 Small Cell Carcinoma of Lung PHASE2 UNKNOWN 2025-06-14 Zhejiang Cancer Hospital, Hang... More >>zhou, Zhejiang, China Less <<
NCT01607554 Non-small Cell Lung Cancer PHASE1|PHASE2 TERMINATED 2025-03-13 Hematology Oncology Associates... More >>, Albuquerque, New Mexico, 87106, United States|University of New Mexico Cancer Center, Albuquerque, New Mexico, 87131, United States|New Mexico Cancer Care Associates, Santa Fe, New Mexico, 87505, United States Less <<
NCT00222443 Lymphomas|Tumors PHASE1 COMPLETED 2025-12-07 Oklahoma University Health Sci... More >>ences Center-Jimmy Everest Center, Oklahoma City, Oklahoma, 73104, United States Less <<
NCT00062842 Cancer PHASE1 COMPLETED 2006-09-12 Texas Children's Hospital, Hou... More >>ston, Texas, 77030, United States Less <<
NCT01239485 Acute Leukemia PHASE1 UNKNOWN 2025-12-13 Seoul National University Hosp... More >>ital, Seoul, Chongno-gu, 110-744, Korea, Republic of Less <<
NCT01963182 First Line Metastatic Colorect... More >>al Cancer Less << PHASE2 COMPLETED 2019-12-09 Clinique de la Chataigneraie, ... More >>Beaumont, 63110, France|Centre Jean Perrin, Clermont-Ferrand, 63011, France|CHU Estaing, Clermont-Ferrand, 63011, France Less <<
NCT00037804 Unspecified Adult Solid Tumor|... More >>Chemotherapy|Liver Dysfunction|Neoplasms, Solid Tumor Less << PHASE1 COMPLETED - Research Center, Detroit, Mich... More >>igan, 48201, United States|Research Center, New Brunswick, New Jersey, 08901, United States|Research Center, Nashville, Tennessee, 37232, United States|Research Center, Marshfield, Wisconsin, 54449, United States Less <<
NCT03329183 Colorectal Cancer PHASE2 UNKNOWN 2025-03-22 Shanghai Changzheng Hospital, ... More >>Shanghai, Shanghai, 200433, China Less <<
NCT03562390 Breast Cancer PHASE2 UNKNOWN 2025-12-21 Cancer Hospital of China Medic... More >>al University, Shenyang, Liaoning, China Less <<
NCT00136955 Uterine Cervical Neoplasms PHASE2 COMPLETED 2025-05-08 Pfizer Investigational Site, K... More >>aoshiung, 813, Taiwan|Pfizer Investigational Site, Kwei-Shan County, TaoYuan,, Taiwan|Pfizer Investigational Site, Taichung, Taiwan|Pfizer Investigational Site, Taipei, 112, Taiwan|Pfizer Investigational Site, Taipei, Taiwan Less <<
NCT00708773 Advanced Cancer PHASE1 COMPLETED 2025-08-16 University of Chicago, Chicago... More >>, Illinois, 60637, United States|NorthShore University HealthSystem, Evanston, Illinois, 60201, United States Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.70mL

0.34mL

0.17mL

8.52mL

1.70mL

0.85mL

17.05mL

3.41mL

1.70mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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