Camptothecin
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MedKoo CAT#: 406279

CAS#: 7689-03-4

Description: Camptothecin (CPT) is a cytotoxic quinoline alkaloid which inhibits the DNA enzyme topoisomerase I (topo I). It was discovered in 1966 by M. E. Wall and M. C. Wani in systematic screening of natural products for anticancer drugs. It was isolated from the bark and stem of Camptotheca acuminata (Camptotheca, Happy tree), a tree native to China used as a cancer treatment in Traditional Chinese Medicine. CPT showed remarkable anticancer activity in preliminary clinical trials but also low solubility and (high) adverse drug reaction. Because of these disadvantages synthetic and medicinal chemists have developed numerous syntheses of Camptothecin and various derivatives to increase the benefits of the chemical, with good results. Two CPT analogues have been approved and are used in cancer chemotherapy today, topotecan and irinotecan.


Chemical Structure

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Camptothecin
CAS# 7689-03-4

Theoretical Analysis

MedKoo Cat#: 406279
Name: Camptothecin
CAS#: 7689-03-4
Chemical Formula: C20H16N2O4
Exact Mass: 348.11101
Molecular Weight: 348.35
Elemental Analysis: C, 68.96; H, 4.63; N, 8.04; O, 18.37

Price and Availability

Size Price Availability Quantity
1.0g USD 120.0 Same day
2.0g USD 190.0 Same day
5.0g USD 350.0 Same day
10.0g USD 650.0 2 Weeks
20.0g USD 950.0 2 Weeks
50.0g USD 1650.0 2 Weeks
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Synonym: Camptothecine; (S)-(+)-Camptothecin; d-Camptothecin; 20(S)-Camptothecine; (+)-Camptothecin; Camptothecin; CPT.

IUPAC/Chemical Name: (S)-4-ethyl-4-hydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione

InChi Key: VSJKWCGYPAHWDS-FQEVSTJZSA-N

InChi Code: InChI=1S/C20H16N2O4/c1-2-20(25)14-8-16-17-12(7-11-5-3-4-6-15(11)21-17)9-22(16)18(23)13(14)10-26-19(20)24/h3-8,25H,2,9-10H2,1H3/t20-/m0/s1

SMILES Code: O=C1[C@](O)(CC)C2=C(CO1)C(N3CC4=CC5=CC=CC=C5N=C4C3=C2)=O

Appearance: Light yellow 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

Biological target: Camptothecin (CPT) is a DNA enzyme topoisomerase I inhibitor with an IC50 of 679 nM.
In vitro activity: Treatment of cells with CPT as well as its derivatives CPT-11 and SN38 influences KMT1A independently of DNA damage induction, which raises the possibility that CPT can modulate KMT1A activity. The effect of CPT on KMT1A activity was examined in an in vitro histone methyltransferase (HMTase) assay. The data shows dose-dependent inhibition of KMT1A methyltransferase activity in the presence of CPT (Figure 6A). Furthermore, a subsequent experiment showed that CPT-11 and SN38 have similar dose-dependent inhibitory effects on KMT1A methyltransferase activity in this assay system (Figure 6B). Collectively, these data demonstrate that CPT can directly inhibit KMT1A activity in vitro. Reference: Oncotarget. 2018 May 25;9(40):25796-25807. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5995248/
In vivo activity: The in vivo effect of CPT-11 on differentiation was evaluated using an Rh30 aRMS (alveolar rhabdomyosarcoma) xenograft model. Tumor-bearing mice were treated with CPT-11 or PBS as a control, and tumor volume was measured weekly. A substantial reduction in tumor growth was observed in treated animals (Supplementary Figure 2B). Tumor sections from CPT-11 treated and control mice were subjected to immunohistochemical (IHC) analysis for MyHC, and proliferation marker Ki-67 following experimental endpoints. A decrease in Ki-67-positive cells and an increase in MyHC-positive cells were evident in tumor sections from CPT-11 treated mice (Figure 3B). Additionally, lysates from tumor samples were analyzed via immunoblot for KMT1A and MyoG expression. The data shows a loss of KMT1A and induction of MyoG from tumors in mice treated with CPT-11 compared to PBS control (Figure 3C), demonstrating these biochemical changes in therapeutically achievable concentrations in mice. Collectively, these data demonstrate that treatment with CPT-11 leads to the suppression of cell and tumor growth coupled with induction of terminal myogenic differentiation in aRMS. Reference: Oncotarget. 2018 May 25;9(40):25796-25807. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5995248/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMF 2.0 5.74
DMSO 3.75 10.77
DMSO:PBS (pH 7.2) (1:3) 0.25 0.72

Preparing Stock Solutions

The following data is based on the product molecular weight 348.35 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. Wolff DW, Lee MH, Jothi M, Mal M, Li F, Mal AK. Camptothecin exhibits topoisomerase1-independent KMT1A suppression and myogenic differentiation in alveolar rhabdomyosarcoma cells. Oncotarget. 2018 May 25;9(40):25796-25807. doi: 10.18632/oncotarget.25376. PMID: 29899822; PMCID: PMC5995248. 2. Gigliotti CL, Minelli R, Cavalli R, Occhipinti S, Barrera G, Pizzimenti S, Cappellano G, Boggio E, Conti L, Fantozzi R, Giovarelli M, Trotta F, Dianzani U, Dianzani C. In Vitro and In Vivo Therapeutic Evaluation of Camptothecin-Encapsulated β-Cyclodextrin Nanosponges in Prostate Cancer. J Biomed Nanotechnol. 2016 Jan;12(1):114-27. doi: 10.1166/jbn.2016.2144. PMID: 27301177.
In vitro protocol: 1. Wolff DW, Lee MH, Jothi M, Mal M, Li F, Mal AK. Camptothecin exhibits topoisomerase1-independent KMT1A suppression and myogenic differentiation in alveolar rhabdomyosarcoma cells. Oncotarget. 2018 May 25;9(40):25796-25807. doi: 10.18632/oncotarget.25376. PMID: 29899822; PMCID: PMC5995248. 2. Gigliotti CL, Minelli R, Cavalli R, Occhipinti S, Barrera G, Pizzimenti S, Cappellano G, Boggio E, Conti L, Fantozzi R, Giovarelli M, Trotta F, Dianzani U, Dianzani C. In Vitro and In Vivo Therapeutic Evaluation of Camptothecin-Encapsulated β-Cyclodextrin Nanosponges in Prostate Cancer. J Biomed Nanotechnol. 2016 Jan;12(1):114-27. doi: 10.1166/jbn.2016.2144. PMID: 27301177.
In vivo protocol: 1. Wolff DW, Lee MH, Jothi M, Mal M, Li F, Mal AK. Camptothecin exhibits topoisomerase1-independent KMT1A suppression and myogenic differentiation in alveolar rhabdomyosarcoma cells. Oncotarget. 2018 May 25;9(40):25796-25807. doi: 10.18632/oncotarget.25376. PMID: 29899822; PMCID: PMC5995248. 2. Gigliotti CL, Minelli R, Cavalli R, Occhipinti S, Barrera G, Pizzimenti S, Cappellano G, Boggio E, Conti L, Fantozzi R, Giovarelli M, Trotta F, Dianzani U, Dianzani C. In Vitro and In Vivo Therapeutic Evaluation of Camptothecin-Encapsulated β-Cyclodextrin Nanosponges in Prostate Cancer. J Biomed Nanotechnol. 2016 Jan;12(1):114-27. doi: 10.1166/jbn.2016.2144. PMID: 27301177.

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1: Bala V, Rao S, Boyd BJ, Prestidge CA. Prodrug and nanomedicine approaches for the delivery of the camptothecin analogue SN38. J Control Release. 2013 Nov 28;172(1):48-61. doi: 10.1016/j.jconrel.2013.07.022. Epub 2013 Aug 6. Review. PubMed PMID: 23928356.

2: Huang Q, Wang L, Lu W. Evolution in medicinal chemistry of E-ring-modified Camptothecin analogs as anticancer agents. Eur J Med Chem. 2013 May;63:746-57. doi: 10.1016/j.ejmech.2013.01.058. Epub 2013 Mar 21. Review. PubMed PMID: 23578545.

3: Beretta GL, Gatti L, Perego P, Zaffaroni N. Camptothecin resistance in cancer: insights into the molecular mechanisms of a DNA-damaging drug. Curr Med Chem. 2013;20(12):1541-65. Review. PubMed PMID: 23432590.

4: Tomicic MT, Kaina B. Topoisomerase degradation, DSB repair, p53 and IAPs in cancer cell resistance to camptothecin-like topoisomerase I inhibitors. Biochim Biophys Acta. 2013 Jan;1835(1):11-27. doi: 10.1016/j.bbcan.2012.09.002. Epub 2012 Sep 21. Review. PubMed PMID: 23006513.

5: Beretta GL, Zuco V, De Cesare M, Perego P, Zaffaroni N. Namitecan: a hydrophilic camptothecin with a promising preclinical profile. Curr Med Chem. 2012;19(21):3488-501. Review. PubMed PMID: 22680917.

6: Mollica A, Stefanucci A, Feliciani F, Cacciatore I, Cornacchia C, Pinnen F. Delivery methods of camptothecin and its hydrosoluble analogue irinotecan for treatment of colorectal cancer. Curr Drug Deliv. 2012 Mar;9(2):122-31. Review. PubMed PMID: 22283650.

7: Beretta GL, Zuco V, Perego P, Zaffaroni N. Targeting DNA topoisomerase I with non-camptothecin poisons. Curr Med Chem. 2012;19(8):1238-57. Review. PubMed PMID: 22204335.

8: Sheng C, Miao Z, Zhang W. New strategies in the discovery of novel non-camptothecin topoisomerase I inhibitors. Curr Med Chem. 2011;18(28):4389-409. Review. PubMed PMID: 21861816.

9: Beretta GL, Cossa G, Gatti L, Zunino F, Perego P. Tyrosyl-DNA phosphodiesterase 1 targeting for modulation of camptothecin-based treatment. Curr Med Chem. 2010;17(15):1500-8. Review. PubMed PMID: 20166932.

10: Sirikantaramas S, Yamazaki M, Saito K. A survival strategy: the coevolution of the camptothecin biosynthetic pathway and self-resistance mechanism. Phytochemistry. 2009 Oct-Nov;70(15-16):1894-8. doi: 10.1016/j.phytochem.2009.07.034. Epub 2009 Aug 24. Review. PubMed PMID: 19709698.



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