Gimatecan

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 201410

CAS#: 292618-32-7

Description: Gimatecan is an orally bioavailable, semi-synthetic lipophilic analogue of camptothecin, a quinoline alkaloid extracted from the Asian tree Camptotheca acuminate, with potential antineoplastic and antiangiogenic activities. Gimatecan binds to and inhibits the activity of topoisomerase I, stabilizing the cleavable complex of topoisomerase I-DNA, which inhibits the religation of single-stranded DNA breaks generated by topoisomerase I; lethal double-stranded DNA breaks occur when the topoisomerase I-DNA complex is encountered by the DNA replication machinery, DNA replication is disrupted, and the tumor cell undergoes apoptosis.


Chemical Structure

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Gimatecan
CAS# 292618-32-7

Theoretical Analysis

MedKoo Cat#: 201410
Name: Gimatecan
CAS#: 292618-32-7
Chemical Formula: C25H25N3O5
Exact Mass: 447.17942
Molecular Weight: 447.4831
Elemental Analysis: C, 67.10; H, 5.63; N, 9.39; O, 17.88

Size Price Shipping out time Quantity
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Pricing updated 2021-02-27. Prices are subject to change without notice.

Gimatecan, is not in stock, but may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.

Synonym: LBQ707; LBQ 707; LB-Q707; ST1481; ST1481; ST-1481; CPT 1847; CPT-1847; CPT1847; Gimatecan;

IUPAC/Chemical Name: (4S)-11-((E)-((1,1-Dimethylethoxy)imino)methyl)-4-ethyl-4-hydroxy-1,12-dihydro-14H-pyrano(3',4':6,7)indolizino(1,2-b)quinoline-3,14(4H)-dione

InChi Key: UIVFUQKYVFCEKJ-OPTOVBNMSA-N

InChi Code: InChI=1S/C25H25N3O5/c1-5-25(31)18-10-20-21-16(12-28(20)22(29)17(18)13-32-23(25)30)15(11-26-33-24(2,3)4)14-8-6-7-9-19(14)27-21/h6-11,31H,5,12-13H2,1-4H3/b26-11+/t25-/m0/s1

SMILES Code: O=C1[C@](O)(CC)C2=C(CO1)C(N3CC4=C(/C=N/OC(C)(C)C)C5=CC=CC=C5N=C4C3=C2)=O

Appearance:
Solid powder

Purity:
>98% (or refer to the Certificate of Analysis)

Shipping Condition:
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs. Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Storage Condition:
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility:
Soluble in DMSO, not in water

Shelf Life:
>5 years if stored properly

Drug Formulation:
This drug may be formulated in DMSO

Stock Solution Storage:
0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code:
2934.99.9001

Handling Instructions:

Preparing Stock Solutions

The following data is based on the product molecular weight 447.4831 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Select a batch to recalculate based on the batch molecular weight:
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL

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This message contains search results from the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM). Do not reply directly to this message

Sent On: Wed Oct 21 21:46:41 2020

Search: Gimatecan

20 selected items

PubMed Results
Items 1-20 of 20 (Display the 20 citations in PubMed)

1: DE Cesare M. High Efficacy of Intravenous Gimatecan on Human Tumor Xenografts. Anticancer Res. 2018 Oct;38(10):5783-5790. doi: 10.21873/anticanres.12917. PMID: 30275200.

2: Minenkova O, Vesci L, De Santis R, Santapaola D, Cincinelli R, Musso L, Dallavalle S, Giannini G. Growth inhibition of human ovarian carcinoma by a novel AvidinOX-anchored biotinylated camptothecin derivative. Bioorg Med Chem Lett. 2018 Nov 1;28(20):3312-3314. doi: 10.1016/j.bmcl.2018.09.017. Epub 2018 Sep 15. PMID: 30243588.

3: Zou J, Li S, Chen Z, Lu Z, Gao J, Zou J, Lin X, Li Y, Zhang C, Shen L. A novel oral camptothecin analog, gimatecan, exhibits superior antitumor efficacy than irinotecan toward esophageal squamous cell carcinoma in vitro and in vivo. Cell Death Dis. 2018 May 31;9(6):661. doi: 10.1038/s41419-018-0700-0. PMID: 29855512; PMCID: PMC5981453.

4: Chen Z, Liu Z, Huang W, Li Z, Zou J, Wang J, Lin X, Li B, Chen D, Hu Y, Ji J, Gao J, Shen L. Gimatecan exerts potent antitumor activity against gastric cancer in vitro and in vivo via AKT and MAPK signaling pathways. J Transl Med. 2017 Dec 13;15(1):253. doi: 10.1186/s12967-017-1360-z. PMID: 29237470; PMCID: PMC5729429.

5: Zhao Y, Lau LF, Dai X, Li B. In Vitro and In Vivo Anticancer Activity of Gimatecan against Hepatocellular Carcinoma. Asian Pac J Cancer Prev. 2016 Nov 1;17(11):4853-4856. doi: 10.22034/APJCP.2016.17.11.4853. PMID: 28030910; PMCID: PMC5454685.

6: Mulholland K, Wu C. Computational Study of Anticancer Drug Resistance Caused by 10 Topisomerase I Mutations, Including 7 Camptothecin Analogs and Lucanthone. J Chem Inf Model. 2016 Sep 26;56(9):1872-83. doi: 10.1021/acs.jcim.6b00317. Epub 2016 Sep 1. PMID: 27564845.

7: Prada CF, Alvarez-Velilla R, Balaña-Fouce R, Prieto C, Calvo-Álvarez E, Escudero-Martínez JM, Requena JM, Ordóñez C, Desideri A, Pérez-Pertejo Y, Reguera RM. 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. doi: 10.1016/j.bcp.2013.02.024. Epub 2013 Mar 1. PMID: 23466420.

8: Lin F, Marchetti S, Pluim D, Iusuf D, Mazzanti R, Schellens JH, Beijnen JH, van Tellingen O. Abcc4 together with abcb1 and abcg2 form a robust cooperative drug efflux system that restricts the brain entry of camptothecin analogues. Clin Cancer Res. 2013 Apr 15;19(8):2084-95. doi: 10.1158/1078-0432.CCR-12-3105. Epub 2013 Mar 5. PMID: 23461902.

9: Hu J, Wen PY, Abrey LE, Fadul CE, Drappatz J, Salem N, Supko JG, Hochberg F. A phase II trial of oral gimatecan for recurrent glioblastoma. J Neurooncol. 2013 Feb;111(3):347-53. doi: 10.1007/s11060-012-1023-0. Epub 2012 Dec 12. PMID: 23232808.

10: Perego P, Cossa G, Tinelli S, Corna E, Carenini N, Gatti L, De Cesare M, Ciusani E, Zunino F, Luison E, Canevari S, Zaffaroni N, Beretta GL. Role of tyrosyl-DNA phosphodiesterase 1 and inter-players in regulation of tumor cell sensitivity to topoisomerase I inhibition. Biochem Pharmacol. 2012 Jan 1;83(1):27-36. doi: 10.1016/j.bcp.2011.09.021. Epub 2011 Sep 29. PMID: 21978643.

11: Biroccio A, Porru M, Rizzo A, Salvati E, D'Angelo C, Orlandi A, Passeri D, Franceschin M, Stevens MF, Gilson E, Beretta G, Zupi G, Pisano C, Zunino F, Leonetti C. DNA damage persistence as determinant of tumor sensitivity to the combination of Topo I inhibitors and telomere-targeting agents. Clin Cancer Res. 2011 Apr 15;17(8):2227-36. doi: 10.1158/1078-0432.CCR-10-3033. Epub 2011 Feb 25. PMID: 21355072.

12: Tomillero A, Moral MA. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2010 Jan-Feb;32(1):47-86. PMID: 20383346.

13: Zucchetti M, Meco D, Di Francesco AM, Servidei T, Patriarca V, Cusano G, D'Incalci M, Forestieri D, Pisano C, Riccardi R. Antitumor activity and pharmacokinetics of oral gimatecan on pediatric cancer xenografts. Cancer Chemother Pharmacol. 2010 Sep;66(4):635-41. doi: 10.1007/s00280-009-1201-8. Epub 2009 Dec 20. PMID: 20091168.

14: Frapolli R, Zucchetti M, Sessa C, Marsoni S, Viganò L, Locatelli A, Rulli E, Compagnoni A, Bello E, Pisano C, Carminati P, D'Incalci M. Clinical pharmacokinetics of the new oral camptothecin gimatecan: the inter-patient variability is related to alpha1-acid glycoprotein plasma levels. Eur J Cancer. 2010 Feb;46(3):505-16. doi: 10.1016/j.ejca.2009.11.006. Epub 2009 Dec 16. PMID: 20007015.

15: Pecorelli S, Ray-Coquard I, Tredan O, Colombo N, Parma G, Tisi G, Katsaròs D, Lhommé C, Lissoni AA, Vermorken JB, du Bois A, Poveda A, Frigerio L, Barbieri P, Carminati P, Brienza S, Guastalla JP. Phase II of oral gimatecan in patients with recurrent epithelial ovarian, fallopian tube or peritoneal cancer, previously treated with platinum and taxanes. Ann Oncol. 2010 Apr;21(4):759-765. doi: 10.1093/annonc/mdp514. Epub 2009 Nov 11. PMID: 19906760; PMCID: PMC2844948.

16: Fabbri F, Brigliadori G, Carloni S, Ulivi P, Tesei A, Silvestrini R, Amadori D, Zoli W. Docetaxel-ST1481 sequence exerts a potent cytotoxic activity on hormone-resistant prostate cancer cells by reducing drug resistance-related gene expression. Prostate. 2010 Feb 1;70(2):219-27. doi: 10.1002/pros.21055. PMID: 19790230.

17: Zuco V, Supino R, Favini E, Tortoreto M, Cincinelli R, Croce AC, Bucci F, Pisano C, Zunino F. Efficacy of ST1968 (namitecan) on a topotecan-resistant squamous cell carcinoma. Biochem Pharmacol. 2010 Feb 15;79(4):535-41. doi: 10.1016/j.bcp.2009.09.012. PMID: 19765546.

18: Pace S, Capocasa F, Tallarico C, Frapolli R, Zucchetti M, Longo A. Determination of total and lactone form of a new camptothecin derivative gimatecan (ST1481) and its metabolite ST1698 in human plasma by high-performance liquid chromatography with fluorimetric detection. J Pharm Biomed Anal. 2009 Oct 15;50(3):507-14. doi: 10.1016/j.jpba.2009.05.019. Epub 2009 May 27. PMID: 19553057.

19: Vekhoff P, Halby L, Oussedik K, Dallavalle S, Merlini L, Mahieu C, Lansiaux A, Bailly C, Boutorine A, Pisano C, Giannini G, Alloatti D, Arimondo PB. Optimized synthesis and enhanced efficacy of novel triplex-forming camptothecin derivatives based on gimatecan. Bioconjug Chem. 2009 Apr;20(4):666-72. doi: 10.1021/bc800494y. PMID: 19309124.

20: Oostendorp RL, van de Steeg E, van der Kruijssen CM, Beijnen JH, Kenworthy KE, Schinkel AH, Schellens JH. Organic anion-transporting polypeptide 1B1 mediates transport of Gimatecan and BNP1350 and can be inhibited by several classic ATP-binding cassette (ABC) B1 and/or ABCG2 inhibitors. Drug Metab Dispos. 2009 Apr;37(4):917-23. doi: 10.1124/dmd.108.024901. Epub 2009 Jan 12. PMID: 19139163.



Additional Information

Phase II study of Gimatecan: From June 2005 to December 2005, 69 assessable patients were enrolled. The best overall response to study treatment by combined CA-125 and RECIST criteria was partial response in 17 patients (24.6%) and disease stabilization in 22 patients (31.9%). The median time to progression and overall survival were 3.8 and 16.2 months, respectively. A total of 312 cycles were administered. Neutropenia grade 4 and thrombocytopenia grade 4 occurred in 17.4% and 7.2% of patients, respectively. Diarrhea grade 4 was never observed. Asthenia and fatigue were reported by 36.2% and 18.8% of patients, but were all grade 2 or less. CONCLUSION: Gimatecan is a new active agent in previously treated ovarian cancer with myelosuppression as main toxicity.   (source: Ann Oncol. 2010 Apr;21(4):759-65.).
Phase II study of Gimatecan: From June 2005 to December 2005, 69 assessable patients were enrolled. The best overall response to study treatment by combined CA-125 and RECIST criteria was partial response in 17 patients (24.6%) and disease stabilization in 22 patients (31.9%). The median time to progression and overall survival were 3.8 and 16.2 months, respectively. A total of 312 cycles were administered. Neutropenia grade 4 and thrombocytopenia grade 4 occurred in 17.4% and 7.2% of patients, respectively. Diarrhea grade 4 was never observed. Asthenia and fatigue were reported by 36.2% and 18.8% of patients, but were all grade 2 or less. CONCLUSION: Gimatecan is a new active agent in previously treated ovarian cancer with myelosuppression as main toxicity.   (source: Ann Oncol. 2010 Apr;21(4):759-65.).