Indotecan
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MedKoo CAT#: 402502

CAS#: 915303-09-2

Description: Indotecan, also known as LMP400, is a novel selective and potent topoisomerase I inhibitor with potential anticancer activitity. Indotecan is currently in Phase I trials.


Chemical Structure

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Indotecan
CAS# 915303-09-2

Theoretical Analysis

MedKoo Cat#: 402502
Name: Indotecan
CAS#: 915303-09-2
Chemical Formula: C26H26N2O7
Exact Mass: 478.174
Molecular Weight: 478.501
Elemental Analysis: C, 65.26; H, 5.48; N, 5.85; O, 23.41

Price and Availability

Size Price Availability Quantity
50.0mg USD 950.0 2 Weeks
100.0mg USD 1650.0 2 Weeks
200.0mg USD 2150.0 2 Weeks
500.0mg USD 3250.0 2 Weeks
1.0g USD 4650.0 2 Weeks
2.0g USD 7850.0 2 Weeks
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Synonym: LMP400; LMP-400; LMP 400; Indotecan.

IUPAC/Chemical Name: 2,3-dimethoxy-6-(3-morpholinopropyl)-5H-[1,3]dioxolo[4',5':5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione

InChi Key: FMFIFGLHVOZDEL-UHFFFAOYSA-N

InChi Code: InChI=1S/C26H26N2O7/c1-31-19-10-15-18(13-20(19)32-2)26(30)28(5-3-4-27-6-8-33-9-7-27)24-16-11-21-22(35-14-34-21)12-17(16)25(29)23(15)24/h10-13H,3-9,14H2,1-2H3

SMILES Code: O=C1N(CCCN2CCOCC2)C3=C(C(C4=C3C=C(OCO5)C5=C4)=O)C6=C1C=C(OC)C(OC)=C6

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.

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: >2 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

Product Data:

Biological target: Indotecan (LMP-400) is a potent topoisomerase 1 (Top1) inhibitor with IC50 values of 300, 1200, 560 nM for P388, HCT116, MCF-7 cell lines, respectively.
In vitro activity: Interestingly, increased KAP1 polypeptide was accompanied by enhanced phosphorylation at Ser824. Similar to gammaH2AX, KAP1 phosphorylation was consistently enhanced in a panel of 12 cell lines and in A375 xenografts following NSC 724998 treatment. In summary, these data enhance our understanding of protein dynamics in the nucleus following DNA damage and provide an alternate marker (pKAP1) with potential for monitoring clinical responses to Top1 poisons. Reference: J Proteome Res. 2010 Aug 6;9(8):4016-27. https://pubmed.ncbi.nlm.nih.gov/20515076/
In vivo activity: Treatment of DU145 xenograft tumors with OTX015 or LMP400 as single agents did not result in any noticeable reduction in tumor growth. In contrast, the combination treatment of OTX015 and LMP400 resulted in a potent reduction in tumor growth (Figure 5, D and E, and Supplemental Table 6). Taken together, these studies present a compelling rationale for combining BETi and TOP1i in the treatment of aggressive cancers. Reference: JCI Insight. 2022 May 9;7(9):e152955. https://pubmed.ncbi.nlm.nih.gov/35349486/

Preparing Stock Solutions

The following data is based on the product molecular weight 478.501 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.

Recalculate based on batch purity %
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
Formulation protocol: 1. Lee HM, Clark EP, Kuijer MB, Cushman M, Pommier Y, Philpot BD. Characterization and structure-activity relationships of indenoisoquinoline-derived topoisomerase I inhibitors in unsilencing the dormant Ube3a gene associated with Angelman syndrome. Mol Autism. 2018 Aug 17;9:45. doi: 10.1186/s13229-018-0228-2. PMID: 30140420; PMCID: PMC6098585. 2. Han B, Stockwin LH, Hancock C, Yu SX, Hollingshead MG, Newton DL. Proteomic analysis of nuclei isolated from cancer cell lines treated with indenoisoquinoline NSC 724998, a novel topoisomerase I inhibitor. J Proteome Res. 2010 Aug 6;9(8):4016-27. doi: 10.1021/pr100194d. Erratum in: J Proteome Res. 2011 Apr 1;10(4):2128. PMID: 20515076; PMCID: PMC2917484. 3. Li X, Baek G, Carreira S, Yuan W, Ma S, Hofstad M, Lee S, Gao Y, Bertan C, Fenor de la Maza MLD, Alluri PG, Burma S, Chen BP, Raj GV, de Bono J, Pommier Y, Mani RS. Targeting radioresistance and replication fork stability in prostate cancer. JCI Insight. 2022 May 9;7(9):e152955. doi: 10.1172/jci.insight.152955. PMID: 35349486; PMCID: PMC9090241. 4. Coussy F, El-Botty R, Château-Joubert S, Dahmani A, Montaudon E, Leboucher S, Morisset L, Painsec P, Sourd L, Huguet L, Nemati F, Servely JL, Larcher T, Vacher S, Briaux A, Reyes C, La Rosa P, Lucotte G, Popova T, Foidart P, Sounni NE, Noel A, Decaudin D, Fuhrmann L, Salomon A, Reyal F, Mueller C, Ter Brugge P, Jonkers J, Poupon MF, Stern MH, Bièche I, Pommier Y, Marangoni E. BRCAness, SLFN11, and RB1 loss predict response to topoisomerase I inhibitors in triple-negative breast cancers. Sci Transl Med. 2020 Feb 19;12(531):eaax2625. doi: 10.1126/scitranslmed.aax2625. PMID: 32075943; PMCID: PMC8662740.
In vitro protocol: 1. Lee HM, Clark EP, Kuijer MB, Cushman M, Pommier Y, Philpot BD. Characterization and structure-activity relationships of indenoisoquinoline-derived topoisomerase I inhibitors in unsilencing the dormant Ube3a gene associated with Angelman syndrome. Mol Autism. 2018 Aug 17;9:45. doi: 10.1186/s13229-018-0228-2. PMID: 30140420; PMCID: PMC6098585. 2. Han B, Stockwin LH, Hancock C, Yu SX, Hollingshead MG, Newton DL. Proteomic analysis of nuclei isolated from cancer cell lines treated with indenoisoquinoline NSC 724998, a novel topoisomerase I inhibitor. J Proteome Res. 2010 Aug 6;9(8):4016-27. doi: 10.1021/pr100194d. Erratum in: J Proteome Res. 2011 Apr 1;10(4):2128. PMID: 20515076; PMCID: PMC2917484.
In vivo protocol: 1. Li X, Baek G, Carreira S, Yuan W, Ma S, Hofstad M, Lee S, Gao Y, Bertan C, Fenor de la Maza MLD, Alluri PG, Burma S, Chen BP, Raj GV, de Bono J, Pommier Y, Mani RS. Targeting radioresistance and replication fork stability in prostate cancer. JCI Insight. 2022 May 9;7(9):e152955. doi: 10.1172/jci.insight.152955. PMID: 35349486; PMCID: PMC9090241. 2. Coussy F, El-Botty R, Château-Joubert S, Dahmani A, Montaudon E, Leboucher S, Morisset L, Painsec P, Sourd L, Huguet L, Nemati F, Servely JL, Larcher T, Vacher S, Briaux A, Reyes C, La Rosa P, Lucotte G, Popova T, Foidart P, Sounni NE, Noel A, Decaudin D, Fuhrmann L, Salomon A, Reyal F, Mueller C, Ter Brugge P, Jonkers J, Poupon MF, Stern MH, Bièche I, Pommier Y, Marangoni E. BRCAness, SLFN11, and RB1 loss predict response to topoisomerase I inhibitors in triple-negative breast cancers. Sci Transl Med. 2020 Feb 19;12(531):eaax2625. doi: 10.1126/scitranslmed.aax2625. PMID: 32075943; PMCID: PMC8662740.

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1: Jossé R, Martin SE, Guha R, Ormanoglu P, Pfister TD, Reaper PM, Barnes CS, Jones J, Charlton P, Pollard JR, Morris J, Doroshow JH, Pommier Y. 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. doi: 10.1158/0008-5472.CAN-13-3369. Epub 2014 Sep 30. PubMed PMID: 25269479; PubMed Central PMCID: PMC4252598.

2: Beck DE, Agama K, Marchand C, Chergui A, Pommier Y, Cushman M. Synthesis and biological evaluation of new carbohydrate-substituted indenoisoquinoline topoisomerase I inhibitors and improved syntheses of the experimental anticancer agents indotecan (LMP400) and indimitecan (LMP776). J Med Chem. 2014 Feb 27;57(4):1495-512. doi: 10.1021/jm401814y. Epub 2014 Feb 11. PubMed PMID: 24517248; PubMed Central PMCID: PMC3983348.

3: Pfister TD, Hollingshead M, Kinders RJ, Zhang Y, Evrard YA, Ji J, Khin SA, Borgel S, Stotler H, Carter J, Divelbiss R, Kummar S, Pommier Y, Parchment RE, Tomaszewski JE, Doroshow JH. Development and validation of an immunoassay for quantification of topoisomerase I in solid tumor tissues. PLoS One. 2012;7(12):e50494. doi: 10.1371/journal.pone.0050494. Epub 2012 Dec 28. PubMed PMID: 23284638; PubMed Central PMCID: PMC3532478.

4: Cinelli MA, Reddy PV, Lv PC, Liang JH, Chen L, Agama K, Pommier Y, van Breemen RB, Cushman M. Identification, synthesis, and biological evaluation of metabolites of the experimental cancer treatment drugs indotecan (LMP400) and indimitecan (LMP776) and investigation of isomerically hydroxylated indenoisoquinoline analogues as topoisomerase I poisons. J Med Chem. 2012 Dec 27;55(24):10844-62. doi: 10.1021/jm300519w. Epub 2012 Dec 7. PubMed PMID: 23215354; PubMed Central PMCID: PMC3542640.

5: Balaña-Fouce R, Prada CF, Requena JM, Cushman M, Pommier Y, Ã



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