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Belotecan Hydrochloride (CKD602)

Alias: CKD-602; Camtobell; Belotecan Hydrochloride; 213819-48-8; Camtobell hydrochloride; Belotecan HCl; CKD-602; CKD 602; Belotecan (hydrochloride); (S)-4-ethyl-4-hydroxy-11-(2-(isopropylamino)ethyl)-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione hydrochloride;CKD 602; CKD602; Belotecan
Cat No.:V6360 Purity: ≥98%
Belotecan HCl (CKD-602), thehydrochloride of CKD602 which isa Topoisomerase I inhibitor, is a semi-synthetic camptothecin analogue with potential antitumor activity.
Belotecan Hydrochloride (CKD602)
Belotecan Hydrochloride (CKD602) Chemical Structure CAS No.: 213819-48-8
Product category: Topoisomerase
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
5mg
10mg
25mg
50mg
100mg
250mg
Other Sizes

Other Forms of Belotecan Hydrochloride (CKD602):

  • Belotecan free base
Official Supplier of:
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Top Publications Citing lnvivochem Products
Purity & Quality Control Documentation

Purity: ≥98%

Product Description

Belotecan HCl (CKD-602), the hydrochloride of CKD602 which is a Topoisomerase I inhibitor, is a semi-synthetic camptothecin analogue with potential antitumor activity. Belotecan binds to topoisomerase I and inhibits its activity, stabilizing the cleavable complex of topoisomerase I-DNA and preventing topoisomerase I from religating single-stranded DNA breaks. Lethal double-stranded DNA breaks happen when the DNA replication machinery comes into contact with the top technicaloisomerase I-DNA complex, disrupting DNA replication and causing the tumor cell to undergo apoptosis. During DNA replication, reversible single-strand breaks in DNA are mediated by the enzyme topoisomerase I.

Biological Activity I Assay Protocols (From Reference)
Targets

Topoisomerase 1

ln Vitro
Belotecan significantly reduces the viability of YD-8, YD-9, and YD-38 cells in a dose- and time-dependent manner; at 72 hours after treatment, the IC50 values are 2.4, 0.18, and 0.05 μg/mL. These cell lines undergo apoptosis when exposed to belotecan. Oral squamous cell cancer cells undergo G2/M phase arrest upon exposure to belotecan[1]. Belotecan has a noteworthy anticancer effect on glioma cells, as evidenced by its IC50 values of 9.07 nM for LN229, 14.57 nM for U251 MG, 29.13 nM for U343 MG, and 84.66 nM for U87 MG [2].
ln Vivo
CKD-602 (7-[2-(N-isopropylamino)ethyl]-(20S)-camptothecin, belotecan), a novel synthetic water-soluble camptothecin derivative, is known to have a significant anticancer effect in vitro on human glioma cell lines, including U87MG and U251MG. In the present study, we evaluated the in vivo antitumor effect of CKD-602 in a mouse glioma model. Nude mice with established U87MG glioma were treated with a dose of CKD-602 of 0mg/kg (control group, injection with saline only; n=5), 40 mg/kg (group A) or 60 mg/kg (group B). Thereafter, the dose was repeated once every 4 days for a total of four doses. Tumor volume was measured histologically and apoptosis was detected using the terminal deoxynucleotide transferase dUTP nick end labeling (TUNEL) assay and immunofluorescence analysis with cleaved caspase-3. Mean tumor volume in each group was: control, 145.35 mm(3); group A, 76.51 mm(3); group B, 73.99 mm(3)). Tumor volume was significantly smaller in both groups A and B compared with the control group (group A, p<0.01; group B, p<0.05). Apoptosis of tumor cells was evident to a greater extent in groups A and B relative to the control group, but there were no significant differences in tumor volume or apoptotic index between groups A and B. These results suggest that CKD-602 has a significant anticancer effect on glioma cells in vivo.[1]
Belotecan significantly inhibits the growth of intracerebral gliomas; animals treated with this drug showed notably smaller tumors than animals in the control group[3].
Cell Assay
CKD-602 7-[2-(N-isopropylamino)ethyl]-(20S)-camptothecin, belotecan) is a synthetic water-soluble camptothecin derivative and topoisomerase inhibitor that has been shown to have clinical anticancer effect against ovarian and lung cancer. We studied its anticancer effects on four human glioma cell lines, U87 MG, U343 MG, U251 MG and LN229. Cell viability was quantified by a modified 2-(2-methoxy-4-nitropheyl)-3-(4-nitropheyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt and significant time- and dose-dependent cytotoxicity was observed in all cell lines. Susceptibility to CKD-602 at 48 h after treatment varied among the four cell lines and their IC50 value was as follows: 9.07 nM (95% CI 0.18-37.42) for LN229, 14.57 nM (95% CI 0.86-47.33) for U251 MG, 29.13 nM (95% CI 0.35-101.23) for U343 MG, and 84.66 nM (95% CI 34.63-148.25) for U87 MG. CKD-602 induced cell cycle arrest at G2 phase and produced antiproliferative activity and apoptosis in all cell lines. Thus, CKD-602 showed a significant anticancer effect on glioma cells in vitro and is a promising candidate for further studies on malignant gliomas.[2]
For 24, 48, and 72 hours, the cells are exposed to varying concentrations of belotecan (0.01, 0.1, 0.5, 1, 5, and 10 μg/mL). Only medium is applied to control samples of every cell line. Using the MTS assay, cell viability is determined[1].
Animal Protocol
Mice: Belotecan is administered intraperitoneally to groups A and B at doses of 40 mg/kg, 60 mg/kg, and 0 mg/kg (control group) in order to treat established U87MG gliomas in naked mice. After that, for a total of four doses, the dose is repeated once every four days. Histological measurements of the tumor volume reveal the presence of apoptosis[1].
References

[1]. Anticancer effects of CKD-602 (Camtobell\u00ae) via G2/M phase arrest in oral squamous cell carcinoma cell lines. Oncol Lett. 2015 Jan;9(1):136-142.

[2]. CKD-602, a camptothecin derivative, inhibits proliferation and induces apoptosis in glioma cell lines. Oncol Rep. 2009 Jun;21(6):1413-9.

[3]. Antitumor activity of CKD-602, a camptothecin derivative, in a mouse glioma model. J Clin Neurosci. 2012 Feb;19(2):301-5

[4]. Lesser Toxicities of Belotecan in Patients with Small Cell Lung Cancer: A Retrospective Single-Center Study of Camptothecin Analogs. Can Respir J. 2016;2016:3576201.

Additional Infomation
Belotecan Hydrochloride is the hydrochloride salt of the semi-synthetic camptothecin analogue belotecan with potential antitumor activity. Belotecan 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. Topoisomerase I is an enzyme that mediates reversible single-strand breaks in DNA during DNA replication.
See also: Belotecan (annotation moved to).
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C25H28CLN3O4
Molecular Weight
469.9605
Exact Mass
469.177
Elemental Analysis
C, 63.89; H, 6.01; Cl, 7.54; N, 8.94; O, 13.62
CAS #
213819-48-8
Related CAS #
256411-32-2; 213819-48-8 (HCl)
PubChem CID
6918340
Appearance
White to yellow solid powder
Boiling Point
772.4ºC at 760mmHg
Flash Point
420.9ºC
Vapour Pressure
4.21E-25mmHg at 25°C
LogP
3.813
Hydrogen Bond Donor Count
3
Hydrogen Bond Acceptor Count
6
Rotatable Bond Count
5
Heavy Atom Count
33
Complexity
865
Defined Atom Stereocenter Count
1
SMILES
Cl[H].O1C([C@](C([H])([H])C([H])([H])[H])(C2C([H])=C3C4C(=C(C5=C([H])C([H])=C([H])C([H])=C5N=4)C([H])([H])C([H])([H])N([H])C([H])(C([H])([H])[H])C([H])([H])[H])C([H])([H])N3C(C=2C1([H])[H])=O)O[H])=O
InChi Key
SJKBXKKZBKCHET-UQIIZPHYSA-N
InChi Code
InChI=1S/C25H27N3O4.ClH/c1-4-25(31)19-11-21-22-17(12-28(21)23(29)18(19)13-32-24(25)30)15(9-10-26-14(2)3)16-7-5-6-8-20(16)27-22;/h5-8,11,14,26,31H,4,9-10,12-13H2,1-3H3;1H/t25-;/m0./s1
Chemical Name
(19S)-19-ethyl-19-hydroxy-10-[2-(propan-2-ylamino)ethyl]-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4,6,8,10,15(20)-heptaene-14,18-dione;hydrochloride
Synonyms
CKD-602; Camtobell; Belotecan Hydrochloride; 213819-48-8; Camtobell hydrochloride; Belotecan HCl; CKD-602; CKD 602; Belotecan (hydrochloride); (S)-4-ethyl-4-hydroxy-11-(2-(isopropylamino)ethyl)-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione hydrochloride;CKD 602; CKD602; Belotecan
HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO: 12.5~47 mg/mL (26.6~100.0 mM)
Water: ~4 mg/mL
Solubility (In Vivo)
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

Injection Formulations
(e.g. IP/IV/IM/SC)
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution 50 μL Tween 80 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO 400 μLPEG300 50 μL Tween 80 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).
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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO 100 μLPEG300 200 μL castor oil 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10: 10 : 80 (i.e. 100 μL Ethanol 100 μL Cremophor 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH 400 μLPEG300 50 μL Tween 80 450 μL Saline)


Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).
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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders


Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 2.1278 mL 10.6392 mL 21.2784 mL
5 mM 0.4256 mL 2.1278 mL 4.2557 mL
10 mM 0.2128 mL 1.0639 mL 2.1278 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

Calculator

Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

  • Calculate the Mass of a compound required to prepare a solution of known volume and concentration
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An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
  • Enter 350.26 in the Molecular Weight (MW) box
  • Enter 10 in the Concentration box and choose the correct unit (mM)
  • Enter 5 in the Volume box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
  • Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
  • Enter 25 into the Concentration (End) box and select the correct unit (mM)
  • Enter 25 into the Volume (End) box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box
g/mol

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:
  • To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.
Definitions of molecular mass, molecular weight, molar mass and molar weight:
  • Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
  • Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.
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Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

  • Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
  • Click the “Calculate” button
  • The answer appears in the Volume (to add to vial) box
In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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Calculation results

Working concentration mg/mL;

Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.

(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
             (2) Be sure to add the solvent(s) in order.

Clinical Trial Information
NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT00430144 Completed Drug: Belotecan
(CKD-602)
Cervical Cancer Sokbom Kang January 2007 Phase 2
NCT01630018 Completed Drug: Belotecan
Drug: Topotecan
Epithelial Ovarian Cancer Chong Kun Dang Pharmaceutical January 2011 Phase 2
NCT00826644 Completed Drug: Belotecan
Drug: Etoposide
Carcinoma, Small Cell Chonnam National University
Hospital
January 2009 Phase 3
NCT00177281 Completed Drug: S CKD602 Cancer University of Pittsburgh September 2003 Phase 1
NCT00754858 Completed Drug: belotecan hydrochloride
Drug: cisplatin
Lung Cancer Yonsei University May 2010 Phase 2
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