Karenitecin (Cositecan) is a topoisomerase I inhibitor (antagonist) with high anti-tumor activity.

Physicochemical Properties

Molecular Formula	C25H28N2O4SI
Molecular Weight	448.59
Exact Mass	448.181
CAS #	203923-89-1
PubChem CID	148202
Appearance	Light yellow to yellow solid powder
Density	1.3±0.1 g/cm3
Boiling Point	727.2±60.0 °C at 760 mmHg
Flash Point	393.6±32.9 °C
Vapour Pressure	0.0±2.5 mmHg at 25°C
Index of Refraction	1.645
LogP	4.14
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	4
Heavy Atom Count	32
Complexity	891
Defined Atom Stereocenter Count	1
SMILES	CC[C@@]1(C2=C(COC1=O)C(=O)N3CC4=C(C5=CC=CC=C5N=C4C3=C2)CC[Si](C)(C)C)O
InChi Key	POADTFBBIXOWFJ-VWLOTQADSA-N
InChi Code	InChI=1S/C25H28N2O4Si/c1-5-25(30)19-12-21-22-17(13-27(21)23(28)18(19)14-31-24(25)29)15(10-11-32(2,3)4)16-8-6-7-9-20(16)26-22/h6-9,12,30H,5,10-11,13-14H2,1-4H3/t25-/m0/s1
Chemical Name	(19S)-19-ethyl-19-hydroxy-10-(2-trimethylsilylethyl)-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
Synonyms	Cositecan, 7-Trimethylsilylethylcamptothecin; BNP 1350, BNP1350, BNP-1350, Karenitecin; MCC 12824, MCC-12824, MCC12824, DB 172, DB172, DB-172
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
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	Topoisomerase I inhibitor Karenitecin has strong anticancer properties. After two hours of treatment, kénitecin reduced the proliferation of A253 cells with IC10, IC50, and IC90 values of 0.01, 0.07, and 0.7 μM, respectively. In A253 cells, kenditecin causes DNA damage (0.01, 0.07, and 0.7 μM) and raises the expression of the cyclin E and cdk2 proteins (0.07 and 0.7 μM). At low doses, kenditecin dramatically increases the cyclin B/cdc2-related kinase activity, whereas at high concentrations, it modestly suppresses this kinase activity [1]. Several human colon cancer cell lines, including COLO205, COLO320, LS174T, SW1398, and WiDr cells, are inhibited by karyanitecin, with IC50 values of 2.4 nM, 1.5 nM, 1.6 nM, 2.9 nM, and 3.2 nM, respectively [2].
ln Vivo	Karenitecin inhibited the maximal development of COLO320 and COLO205 colon cancer cells by intraperitoneal injection at a dose of 1 mg/kg in mice, 61% and 54%, respectively. Karenitecin (1.0 mg/kg × 5 ip daily) notably reduced the growth inhibition of Pgp-positive and Pgp-negative parental xenografts [2].
References	[1]. Characterization of protein kinase chk1 essential for the cell cycle checkpoint after exposure of human head and neck carcinoma A253 cells to a novel topoisomerase I inhibitor BNP1350. Mol Pharmacol. 2000 Mar;57(3):453-9. [2]. New highly lipophilic camptothecin BNP1350 is an effective drug in experimental human cancer. Int J Cancer. 2000 Oct 15;88(2):260-6.
Additional Infomation	Cositecan is a pyranoindolizinoquinoline. Cositecan is the novel camptothecin derivative which is also known as Karenitecin. It has been developed for superior oral bioavailability and increased lactone stability. It is used to treat cancer. Cositecan is a synthetic silicon-containing agent related to camptothecin with antineoplastic properties. Cositecan stabilizes the cleavable complex between topoisomerase I and DNA, resulting in DNA breaks and consequently triggering apoptosis. Because it is lipophilic, cositecan exhibits enhanced tissue penetration and bio-availability compared to water-soluble camptothecins. Drug Indication Investigated for use/treatment in brain cancer, lung cancer, and melanoma. Mechanism of Action BNP1350, 7-[(2-trimethylsilyl)ethyl]-20(S)-camptothecin, is a novel semi-synthetic, highly lipophilic, silicon-containing camptothecin and an inhibitor of topoisomerase I. It has been supercomputer engineered for superior oral bioavailability, superior lactone stability, broad anti-tumor activity, increased potency and insensitivity to Pgp/MRP/LRP drug resistance.

Solubility Data

Solubility (In Vitro)

DMSO : ~3.03 mg/mL (~6.75 mM)

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 : PEG300 ：Tween 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). 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 : PEG300：Tween 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). 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	2.2292 mL	11.1460 mL	22.2921 mL
	5 mM	0.4458 mL	2.2292 mL	4.4584 mL
	10 mM	0.2229 mL	1.1146 mL	2.2292 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.