Belotecan Hydrochloride
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MedKoo CAT#: 526096

CAS#: 213819-48-8 (HCl)

Description: Belotecan, also known as CKD-602, is 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 top technicaloisomerase 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.

Chemical Structure

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Belotecan Hydrochloride
CAS# 213819-48-8 (HCl)
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 526096
Name: Belotecan Hydrochloride
CAS#: 213819-48-8 (HCl)
Chemical Formula: C25H28ClN3O4
Exact Mass: 0.00
Molecular Weight: 469.966
Elemental Analysis: C, 63.89; H, 6.01; Cl, 7.54; N, 8.94; O, 13.62

Price and Availability

Size Price Availability Quantity
10mg USD 150 Ready to Ship
25mg USD 250 Ready to Ship
50mg USD 450 Ready to Ship
100mg USD 750 Ready to Ship
200mg USD 1250 Ready to Ship
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Related CAS #: 256411-32-2 (free base)   213819-48-8 (HCl)    

Synonym: Belotecan Hydrochloride, Camtobell, CKD602, CKD-602, CKD 602, Belotecan

IUPAC/Chemical Name: (4S)-4-Ethyl-4-hydroxy-11-[2-[(1-methylethyl)amino]-ethyl]-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)dione hydrochloride

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

SMILES Code: O=C1[C@](O)(CC)C2=C(CO1)C(N3CC4=C(CCNC(C)C)C5=CC=CC=C5N=C4C3=C2)=O.[H]Cl

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

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

More Info:

Biological target: Belotecan hydrochloride is a Topoisomerase I inhibitor.
In vitro activity: Treatment with CKD-602 showed a significant cytotoxic effect in all cervical cancer cell lines in a time- (p < 0.05) and dose- (p < 0.05) dependent manner (Additional file 1: Figure S1). The IC50 (50% inhibition concentration of cell viability) values were 30 ng/ml (95% CI: 18.29–63.30) for Caski cells, 150 ng/ml (95% CI: 100.3–179.4) for HeLa cells, and 150 ng/ml (95% CI: 64.63–254.3) for SiHa cells at 48 h after treatment. To investigate the efficacy of CKD-602 in cervical cancer, pro-apoptotic activity was measured. A strong pro-apoptotic activity was observed in the treatment groups after 48 h of treatment (Fig. 1a and b). Compared to the control, apoptosis rates significantly increased in Caski, HeLa and Siha when treated with different concentrations (half the IC50 and IC50 values). The treatment increased the expression of PARP, cleaved PARP and Bcl2-associated X protein (BAX). In addition, expression of both p53 and phosphorylated p53 (Ser15) was increased (Fig. 1c). Reference: Mol Med. 2019 May 28;25(1):23. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6540464/
In vivo activity: It was investigated whether CKD-602 would be effective in an in vivo model. Groups of BALB/c-nude mice (five per group) were subcutaneously injected with CaSki cells and then treated (intravenously) with CKD-602 (25 m/kg) or PBS two weeks after the transplantation, when the tumors were approximately 80 mm3 (Fig. 4a). Seventeen days after the last injections, the mice were killed and the tumor volume measured and body weights of the mice recorded (Fig. 4b). Treatment with CKD-602 significantly inhibited the tumor growth of in this xenograft model compared with the control (p < 0.05). There was no significant difference in body weight between the xenograft mice and the controls, indicating that treatment with CKD-602 was well tolerated (Fig. 4b). Reference: Mol Med. 2019 May 28;25(1):23. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6540464/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 48.5 103.20
Water 4.0 8.51

Preparing Stock Solutions

The following data is based on the product molecular weight 469.97 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 S, Ho JY, Liu JJ, Lee H, Park JY, Baik M, Ko M, Lee SU, Choi YJ, Hur SY. CKD-602, a topoisomerase I inhibitor, induces apoptosis and cell-cycle arrest and inhibits invasion in cervical cancer. Mol Med. 2019 May 28;25(1):23. doi: 10.1186/s10020-019-0089-y. PMID: 31138113; PMCID: PMC6540464.
In vitro protocol: 1. Lee S, Ho JY, Liu JJ, Lee H, Park JY, Baik M, Ko M, Lee SU, Choi YJ, Hur SY. CKD-602, a topoisomerase I inhibitor, induces apoptosis and cell-cycle arrest and inhibits invasion in cervical cancer. Mol Med. 2019 May 28;25(1):23. doi: 10.1186/s10020-019-0089-y. PMID: 31138113; PMCID: PMC6540464.
In vivo protocol: 1. Lee S, Ho JY, Liu JJ, Lee H, Park JY, Baik M, Ko M, Lee SU, Choi YJ, Hur SY. CKD-602, a topoisomerase I inhibitor, induces apoptosis and cell-cycle arrest and inhibits invasion in cervical cancer. Mol Med. 2019 May 28;25(1):23. doi: 10.1186/s10020-019-0089-y. PMID: 31138113; PMCID: PMC6540464.

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1: Park YH, Chung CU, Park BM, Park MR, Park DI, Moon JY, Park HS, Kim JH, Jung SS, Kim JO, Kim SY, Lee JE. 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. doi: 10.1155/2016/3576201. Epub 2016 Nov 27. PubMed PMID: 28018128; PubMed Central PMCID: PMC5149640.

2: Oh IJ, Kim KS, Park CK, Kim YC, Lee KH, Jeong JH, Kim SY, Lee JE, Shin KC, Jang TW, Lee HK, Lee KY, Lee SY. Belotecan/cisplatin versus etoposide/cisplatin in previously untreated patients with extensive-stage small cell lung carcinoma: a multi-center randomized phase III trial. BMC Cancer. 2016 Aug 26;16:690. doi: 10.1186/s12885-016-2741-z. PubMed PMID: 27566413; PubMed Central PMCID: PMC5002146.

3: 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. PubMed PMID: 27564845.

4: Ataei S, Yilmaz S, Ertan-Bolelli T, Yildiz I. Generated 3D-common feature hypotheses using the HipHop method for developing new topoisomerase I inhibitors. Arch Pharm (Weinheim). 2015 Jul;348(7):498-507. doi: 10.1002/ardp.201500045. Epub 2015 Apr 27. PubMed PMID: 25914208.

5: Liu YQ, Li WQ, Morris-Natschke SL, Qian K, Yang L, Zhu GX, Wu XB, Chen AL, Zhang SY, Nan X, Lee KH. Perspectives on biologically active camptothecin derivatives. Med Res Rev. 2015 Jul;35(4):753-89. doi: 10.1002/med.21342. Epub 2015 Mar 21. Review. PubMed PMID: 25808858; PubMed Central PMCID: PMC4465867.

6: Kim YK, Koo NY, Yun PY. Anticancer effects of CKD-602 (Camtobell(®)) via G2/M phase arrest in oral squamous cell carcinoma cell lines. Oncol Lett. 2015 Jan;9(1):136-142. Epub 2014 Oct 30. PubMed PMID: 25435947; PubMed Central PMCID: PMC4246617.

7: Chan BA, Coward JI. Chemotherapy advances in small-cell lung cancer. J Thorac Dis. 2013 Oct;5 Suppl 5:S565-78. doi: 10.3978/j.issn.2072-1439.2013.07.43. Review. PubMed PMID: 24163749; PubMed Central PMCID: PMC3804877.

8: Lee GJ, Min JW, Seo MW, Lee MY, Jin JY. Durable response after just one cycle of belotecan-based chemotherapy in a patient with relapsed primary peritoneal serous carcinoma. J Obstet Gynaecol Res. 2014 Jan;40(1):297-300. doi: 10.1111/jog.12161. Epub 2013 Sep 19. PubMed PMID: 24102892.

9: Yeo CD, Lee SH, Kim JS, Kim SJ, Kim SC, Kim YK, Kang HH, Yoon HK, Song JS, Moon HS, Kim JW, Kim KH, Shim BY, Kim CH. A multicenter phase II study of belotecan, a new camptothecin analogue, in elderly patients with previously untreated, extensive-stage small cell lung cancer. Cancer Chemother Pharmacol. 2013 Oct;72(4):809-14. doi: 10.1007/s00280-013-2256-0. Epub 2013 Aug 6. PubMed PMID: 23918044.

10: Lim S, Cho BC, Jung JY, Kim GM, Kim SH, Kim HR, Kim HS, Lim SM, Park JS, Lee JH, Kim D, Kim EY, Park MS, Kim YS, Kim SK, Chang J, Kim JH. Phase II study of camtobell inj. (belotecan) in combination with cisplatin in patients with previously untreated, extensive stage small cell lung cancer. Lung Cancer. 2013 Jun;80(3):313-8. doi: 10.1016/j.lungcan.2013.02.009. Epub 2013 Mar 16. PubMed PMID: 23510628.

11: Kim YH, Lee JK, Kim B, DeWitt JP, Lee JE, Han JH, Kim SK, Oh CW, Kim CY. Combination therapy of cilengitide with belotecan against experimental glioblastoma. Int J Cancer. 2013 Aug 1;133(3):749-56. doi: 10.1002/ijc.28058. Epub 2013 Feb 27. PubMed PMID: 23354807.

12: Wu H, Ramanathan RK, Zamboni BA, Strychor S, Ramalingam S, Edwards RP, Friedland DM, Stoller RG, Belani CP, Maruca LJ, Bang YJ, Zamboni WC. Mechanism-based model characterizing bidirectional interaction between PEGylated liposomal CKD-602 (S-CKD602) and monocytes in cancer patients. Int J Nanomedicine. 2012;7:5555-64. doi: 10.2147/IJN.S35751. Epub 2012 Oct 19. PubMed PMID: 23112576; PubMed Central PMCID: PMC3480239.

13: Lee SW, Kim YM, Kim MB, Kim DY, Kim JH, Nam JH, Kim YT. In vitro chemosensitivity using the histoculture drug response assay in human epithelial ovarian cancer. Acta Med Okayama. 2012;66(3):271-7. PubMed PMID: 22729108.

14: Kim GM, Kim YS, Ae Kang Y, Jeong JH, Kim SM, Hong YK, Sung JH, Lim ST, Kim JH, Kim SK, Cho BC. Efficacy and toxicity of belotecan for relapsed or refractory small cell lung cancer patients. J Thorac Oncol. 2012 Apr;7(4):731-6. doi: 10.1097/JTO.0b013e31824b23cb. PubMed PMID: 22425922.

15: Hwang JH, Yoo HJ, Lim MC, Seo SS, Park SY, Kang S. Phase I clinical trial of alternating belotecan and oral etoposide in patients with platinum-resistant or heavily treated ovarian cancer. Anticancer Drugs. 2012 Mar;23(3):321-5. doi: 10.1097/CAD.0b013e32834ea5d0. PubMed PMID: 22156765.

16: Kim CY, Lee SJ, Kim SK, Park CK, Wang KC, Cho BK. Antitumor activity of CKD-602, a camptothecin derivative, in a mouse glioma model. J Clin Neurosci. 2012 Feb;19(2):301-5. doi: 10.1016/j.jocn.2011.03.032. Epub 2011 Dec 9. PubMed PMID: 22154203.

17: Caron WP, Clewell H, Dedrick R, Ramanathan RK, Davis WL, Yu N, Tonda M, Schellens JH, Beijnen JH, Zamboni WC. Allometric scaling of pegylated liposomal anticancer drugs. J Pharmacokinet Pharmacodyn. 2011 Oct;38(5):653-69. doi: 10.1007/s10928-011-9213-5. Epub 2011 Aug 24. PubMed PMID: 21863380.

18: Hong J, Jung M, Kim YJ, Sym SJ, Kyung SY, Park J, Lee SP, Park JW, Cho EK, Jeong SH, Shin DB, Lee JH. Phase II study of combined belotecan and cisplatin as first-line chemotherapy in patients with extensive disease of small cell lung cancer. Cancer Chemother Pharmacol. 2012 Jan;69(1):215-20. doi: 10.1007/s00280-011-1689-6. Epub 2011 Jun 21. PubMed PMID: 21691745.

19: Choi CH, Lee YY, Song TJ, Park HS, Kim MK, Kim TJ, Lee JW, Lee JH, Bae DS, Kim BG. Phase II study of belotecan, a camptothecin analogue, in combination with carboplatin for the treatment of recurrent ovarian cancer. Cancer. 2011 May 15;117(10):2104-11. doi: 10.1002/cncr.25710. Epub 2010 Nov 29. PubMed PMID: 21523722.

20: Hwang JH, Lim MC, Seo SS, Park SY, Kang S. Phase II study of belotecan (CKD 602) as a single agent in patients with recurrent or progressive carcinoma of uterine cervix. Jpn J Clin Oncol. 2011 May;41(5):624-9. doi: 10.1093/jjco/hyr017. Epub 2011 Feb 24. PubMed PMID: 21355002.