Topotecan HCl | CAS#123948-87-8 | topoisomerase inhibitor

MedKoo Cat#: 100870 | Name: Topotecan HCl

Description:

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

Topotecan is a topoisomerase inhibitor. It is a synthetic, water-soluble analog of the natural chemical compound camptothecin. In physiological environments, topotecan is in equilibrium with its inactive carboxylate form. Topotecan's active lactone form intercalates between DNA bases in the topoisomerase-I cleavage complex. The binding of topotecan in the cleavage complex prevents topoisomerase-I from religating the nicked DNA strand after relieving the strain. This intercalation therefore traps the topoisomerase-I in the cleavage complex bound to the DNA. When the replication-fork collides with the trapped topoisomerase-I, DNA damage occurs. This disruption prevents DNA replication and ultimately leads to cell death.

Chemical Structure

Topotecan HCl

CAS#119413-54-6 (HCl)

Theoretical Analysis

MedKoo Cat#: 100870

Name: Topotecan HCl

CAS#: 119413-54-6 (HCl)

Chemical Formula: C23H24ClN3O5

Exact Mass: 0.0000

Molecular Weight: 457.91

Elemental Analysis: C, 60.33; H, 5.28; Cl, 7.74; N, 9.18; O, 17.47

Price and Availability

Size	Price	Availability
10mg	USD 75.00	Ready to Ship
100mg	USD 150.00	Ready to ship
500mg	USD 250.00	Ready to ship
1g	USD 450.00	Ready to ship
2g	USD 750.00	Ready to ship
5g	USD 1,650.00	Ready to ship
10g	USD 2,950.00	Ready to ship

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Related CAS #

123948-88-9 (acetate) 123948-87-8 (free base) 119413-54-6 (HCl)

Synonym

NSC 609699 NSC-609699 NSC609699; SKF S104864A. SKF 104864 A; SKF-104864-A; SKF104864A; TOPO. Hycamtamine; Hycamtin Hydrochloride; Nogitecan Hydrochloride; Topotecan; Nogitecan Hydrochloride; US brand name: Hycamtin.

IUPAC/Chemical Name

(S)-10-((dimethylamino)methyl)-4-ethyl-4,9-dihydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione hydrochloride

InChi Key

DGHHQBMTXTWTJV-BQAIUKQQSA-N

InChi Code

InChI=1S/C23H23N3O5.ClH/c1-4-23(30)16-8-18-20-12(9-26(18)21(28)15(16)11-31-22(23)29)7-13-14(10-25(2)3)19(27)6-5-17(13)24-20;/h5-8,27,30H,4,9-11H2,1-3H3;1H/t23-;/m0./s1

SMILES Code

O=C1[C@](O)(CC)C2=C(CO1)C(N3CC4=CC5=C(CN(C)C)C(O)=CC=C5N=C4C3=C2)=O.[H]Cl

Appearance

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

More Info

HYCAMTIN (topotecan hydrochloride) is a semi-synthetic derivative of camptothecin and is an anti-tumor drug with topoisomerase I-inhibitory activity. HYCAMTIN for Injection is supplied as a sterile lyophilized, buffered, light yellow to greenish powder available in single-dose vials. Each vial contains topotecan hydrochloride equivalent to 4 mg of topotecan as free base. The reconstituted solution ranges in color from yellow to yellow-green and is intended for administration by intravenous infusion. Inactive ingredients are mannitol, 48 mg, and tartaric acid, 20 mg. Hydrochloric acid and sodium hydroxide may be used to adjust the pH. The solution pH ranges from 2.5 to 3.5. FDA approved for treating: ovarian cancer (FDA May 1996); cervical cancer (FDA June 2006); small cell lung cancer (SCLC) (FDA Oct 2007). FDA approved for treating: ovarian cancer (FDA May 1996); cervical cancer (FDA June 2006); small cell lung cancer (SCLC) (FDA Oct 2007).

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#C23R11B29

View CoA: current batch, Lot#EOS50323

QC Data

View QC data: current batch, Lot#C23R11B29

View QC data: current batch, Lot#EOS50323

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Topotecan Hydrochloride (SKF 104864A Hydrochloride) is a Topoisomerase I inhibitor.

In vitro activity:

Topotecan [(S)-9-dimethylaminomethyl-10-hydroxycampto-thecin hydrochloride; SK&F 104864-A, NSC 609699], a water soluble semisynthetic analogue of the alkaloid campto-thecin, is a potent topoisomerase I inhibitor. Topotecan stabilizes topoisomerase l/DNA cleavable complexes in radiation-resistant human B-lineage acute lymphoblastic leukemia (ALL) cells, causes rapid apoptotic cell death despite high-level expression of bcl-2 protein, and inhibits ALL cell in vitro clonogenic growth in a dose-dependent fashion. As shown in Figs 3 and 4, the examination of topotecan-treated RS4: l l cells by transmission electron microscopy confirmed the presence of multiple apoptosis-associated ultrastructural changes involving both the cytosol and the nucleus. The changes in the cytosol included development of translucent cytoplasmic vacuoles, condensation leading to compaction of organelles, disappearance of microvilli with concomitant formation of blunt protuberances from the cell surface (blebbing), and separation of surface protuberances with plas-malemmal sealing to produce membrane-bound apoptotic bodies of spherical or ovoidal shape. Reference: Blood. 1995 May 15;85(10):2817-28. https://www.sciencedirect.com/science/article/pii/S0006497120764554?via%3Dihub

In vivo activity:

SCID mouse models of human B-lineage acute lymphoblastic leukemia (ALL) were used to evaluate the antileukemic efficacy of topotecan administered subcutaneously over 72 hours. Treatment with topotecan significantly improved event-free survival of SCID mice challenged with RS4;11 cells. Significantly higher cumulative proportions of topotecan-treated SCID mice remained alive without evidence of leukemia as compared with PBS-treated SCID mice (P < .000001 for 200 μg topotecan as well as 400 μg topotecan). Furthermore, time to event (paraplegia or death) in topotecan-treated groups was significantly delayed as compared with the PBS-treated group (Fig 9A). Reference: Blood. 1995 May 15;85(10):2817-28. https://www.sciencedirect.com/science/article/pii/S0006497120764554?via%3Dihub

	Solvent	mg/mL	mM
Solubility
	Water	56.7	123.85
	DMSO	43.0	93.80
	DMSO:PBS (pH 7.2) (1:1)	0.5	1.09

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 457.91 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.

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. Uckun FM, Stewart CF, Reaman G, Chelstrom LM, Jin J, Chandan-Langlie M, Waddick KG, White J, Evans WE. In vitro and in vivo activity of topotecan against human B-lineage acute lymphoblastic leukemia cells. Blood. 1995 May 15;85(10):2817-28. PMID: 7742543.

In vitro protocol:

In vivo protocol:

1: Alshammari MK, Alghazwni MK, Alharbi AS, Alqurashi GG, Kamal M, Alnufaie SR, Alshammari SS, Alshehri BA, Tayeb RH, Bougeis RJM, Aljehani AA, Alotaibi NM, Abida A, Imran M. Nanoplatform for the Delivery of Topotecan in the Cancer Milieu: An Appraisal of its Therapeutic Efficacy. Cancers (Basel). 2022 Dec 22;15(1):65. doi: 10.3390/cancers15010065. PMID: 36612067; PMCID: PMC9817931. 2: Mills H, Acquah R, Tang N, Cheung L, Klenk S, Glassen R, Pirson M, Albert A, Hoang DT, Van TN. A Critical Scrutiny on Liposomal Nanoparticles Drug Carriers as Modelled by Topotecan Encapsulation and Release in Treating Cancer. Evid Based Complement Alternat Med. 2022 Aug 9;2022:7702512. doi: 10.1155/2022/7702512. Retraction in: Evid Based Complement Alternat Med. 2023 Dec 13;2023:9816492. doi: 10.1155/2023/9816492. PMID: 35983007; PMCID: PMC9381203. 3: Drugs and Lactation Database (LactMed®) [Internet]. Bethesda (MD): National Institute of Child Health and Human Development; 2006–. Topotecan. 2021 Aug 16. PMID: 30372006. 4: Upadhyayula PS, Spinazzi EF, Argenziano MG, Canoll P, Bruce JN. Convection Enhanced Delivery of Topotecan for Gliomas: A Single-Center Experience. Pharmaceutics. 2020 Dec 30;13(1):39. doi: 10.3390/pharmaceutics13010039. PMID: 33396668; PMCID: PMC7823846. 5: Rosen VM, Guerra I, McCormack M, Nogueira-Rodrigues A, Sasse A, Munk VC, Shang A. Systematic Review and Network Meta-Analysis of Bevacizumab Plus First- Line Topotecan-Paclitaxel or Cisplatin-Paclitaxel Versus Non-Bevacizumab- Containing Therapies in Persistent, Recurrent, or Metastatic Cervical Cancer. Int J Gynecol Cancer. 2017 Jul;27(6):1237-1246. doi: 10.1097/IGC.0000000000001000. PMID: 28448304; PMCID: PMC5499964. 6: Saraf S, Jain A, Hurkat P, Jain SK. Topotecan Liposomes: A Visit from a Molecular to a Therapeutic Platform. Crit Rev Ther Drug Carrier Syst. 2016;33(5):401-432. doi: 10.1615/CritRevTherDrugCarrierSyst.2016015926. PMID: 27910741. 7: Bracher F, Tremmel T. From Lead to Drug Utilizing a Mannich Reaction: The Topotecan Story. Arch Pharm (Weinheim). 2017 Jul;350(7). doi: 10.1002/ardp.201600236. Epub 2016 Nov 2. PMID: 27805723. 8: Rao V, Bauer F, Vredenburgh JJ. Refractory Small Cell Carcinoma of the Ovary - Hypercalcemic Type (SCCOHT) Treated with Romidepsin and Topotecan: A Case Report and Review of the Literature. Conn Med. 2016 Oct;80(9):529-532. PMID: 29772136. 9: Vennepureddy A, Atallah JP, Terjanian T. Role of Topotecan in Non-Small Cell Lung Cancer: A Review of Literature. World J Oncol. 2015 Oct;6(5):429-436. doi: 10.14740/wjon950e. Epub 2015 Oct 26. PMID: 28983343; PMCID: PMC5624667. 10: Francis JH, Marr BP, Schaiquevich P, Kellick MG, Abramson DH. Properties and clinical utility of topotecan fluorescence: uses for retinoblastoma. Br J Ophthalmol. 2015 Oct;99(10):1320-2. doi: 10.1136/bjophthalmol-2015-306633. Epub 2015 Apr 29. PMID: 25926516. 11: Edwards SJ, Barton S, Thurgar E, Trevor N. Topotecan, pegylated liposomal doxorubicin hydrochloride, paclitaxel, trabectedin and gemcitabine for advanced recurrent or refractory ovarian cancer: a systematic review and economic evaluation. Health Technol Assess. 2015 Jan;19(7):1-480. doi: 10.3310/hta19070. PMID: 25626481; PMCID: PMC4781035. 12: Schaiquevich P, Carcaboso AM, Buitrago E, Taich P, Opezzo J, Bramuglia G, Chantada GL. Ocular pharmacology of topotecan and its activity in retinoblastoma. Retina. 2014 Sep;34(9):1719-27. doi: 10.1097/IAE.0000000000000253. PMID: 25099219. 13: Musa F, Blank S, Muggia F. A pharmacokinetic evaluation of topotecan as a cervical cancer therapy. Expert Opin Drug Metab Toxicol. 2013 Feb;9(2):215-24. doi: 10.1517/17425255.2013.758249. PMID: 23320990. 14: Riemsma R, Simons JP, Bashir Z, Gooch CL, Kleijnen J. Systematic Review of topotecan (Hycamtin) in relapsed small cell lung cancer. BMC Cancer. 2010 Aug 17;10:436. doi: 10.1186/1471-2407-10-436. PMID: 20716361; PMCID: PMC2931489. 15: Hartwell D, Jones J, Loveman E, Harris P, Clegg A, Bird A. Topotecan for relapsed small cell lung cancer: a systematic review and economic evaluation. Cancer Treat Rev. 2011 May;37(3):242-9. doi: 10.1016/j.ctrv.2010.07.005. Epub 2010 Aug 14. PMID: 20709456. 16: Pirker R, Berzinec P, Brincat S, Kasan P, Ostoros G, Pesek M, Plāte S, Purkalne G, Rooneem R, Skricková J, Stanculeanu D, Timcheva C, Tzekova V, Zakotnik B, Zielinski CC, Zwitter M. Therapy of small cell lung cancer with emphasis on oral topotecan. Lung Cancer. 2010 Oct;70(1):7-13. doi: 10.1016/j.lungcan.2010.05.020. Epub 2010 Jun 23. PMID: 20576312. 17: Paton F, Paulden M, Saramago P, Manca A, Misso K, Palmer S, Eastwood A. Topotecan for the treatment of recurrent and stage IVB carcinoma of the cervix. Health Technol Assess. 2010 May;14 Suppl 1:55-62. doi: 10.3310/hta14Suppl1/08. PMID: 20507804. 18: Loveman E, Jones J, Hartwell D, Bird A, Harris P, Welch K, Clegg A. The clinical effectiveness and cost-effectiveness of topotecan for small cell lung cancer: a systematic review and economic evaluation. Health Technol Assess. 2010 Mar;14(19):1-204. doi: 10.3310/hta14190. PMID: 20356561. 19: Lorusso D, Pietragalla A, Mainenti S, Masciullo V, Di Vagno G, Scambia G. Review role of topotecan in gynaecological cancers: current indications and perspectives. Crit Rev Oncol Hematol. 2010 Jun;74(3):163-74. doi: 10.1016/j.critrevonc.2009.08.001. Epub 2009 Sep 18. PMID: 19766512. 20: Sehouli J, Oskay-Ozcelik G. Current role and future aspects of topotecan in relapsed ovarian cancer. Curr Med Res Opin. 2009 Mar;25(3):639-51. doi: 10.1185/03007990802707139. PMID: 19232038.