Namitecan (ST-1968) is a novel, potent and water-soluble camptothecin analog with high antitumor activity, acting as a topoisomerase I inhibitor. ST1968 exhibited an impressive activity against several tumors including models of ovarian and colon carcinoma in which a high rate of cures was observed. t ST1968 was able to overcome the most relevant mechanisms associated with the development of topotecan resistance (i.e., slow proliferation and target downregulation) owing to its peculiar pharmacokinetic behaviour.

Physicochemical Properties

Molecular Formula	C23H22N4O5
Molecular Weight	434.452
Exact Mass	434.159
CAS #	372105-27-6
Related CAS #	372105-27-6;
PubChem CID	10950142
Appearance	Light yellow to yellow solid powder
LogP	2.089
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	5
Heavy Atom Count	32
Complexity	899
Defined Atom Stereocenter Count	1
SMILES	CC[C@@]1(C2=C(COC1=O)C(=O)N3CC4=C(C5=CC=CC=C5N=C4C3=C2)/C=N/OCCN)O
InChi Key	IBTISPLPBBHVSU-UVOOVGFISA-N
InChi Code	InChI=1S/C23H22N4O5/c1-2-23(30)17-9-19-20-15(11-27(19)21(28)16(17)12-31-22(23)29)14(10-25-32-8-7-24)13-5-3-4-6-18(13)26-20/h3-6,9-10,30H,2,7-8,11-12,24H2,1H3/b25-10+/t23-/m0/s1
Chemical Name	(4S)-11-((E)-((2-Aminoethoxy)imino)methyl)-4-ethyl-4-hydroxy-1,12-dihydro-14H-pyrano(3',4'
Synonyms	ST-1968 ST 1968 ST1968
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	Cetuximab and namitecan work together to suppress EGFR expression. In various cell lines, namitecan causes an EGFR expression reduction that is dose-dependent [1]. A431 and A431/TPT cells undergo similar degrees of apoptosis when exposed to ST1968, with IC50 values of 0.21 and 0.29 μM, respectively [2].
ln Vivo	In SCC models, a combination of cetuximab (1 mg/mouse) and napitecan (10 mg/kg) causes synergistic antitumor effects based on the copy number of the EGFR gene [1]. There were no hazardous deaths and a tolerable weight loss with ST1968 (25 mg/kg). In mice bearing A431 tumors, ST1968 elicited a 100% complete response rate and continued to exhibit meaningful activity in tumors resistant to topotecan [2].
References	[1]. Synergistic antitumor activity of cetuximab and namitecan in human squamous cell carcinoma models relies on cooperative inhibition of EGFR expression and depends on high EGFR gene copy number. Clin Cancer Res. 2014 Feb 15;20(4):995-100. [2]. Efficacy of ST1968 (namitecan) on a topotecan-resistant squamous cell carcinoma. Biochem Pharmacol. 2010 Feb 15;79(4):535-41.
Additional Infomation	Namitecan has been used in trials studying the treatment of Solid Tumors.

Solubility Data

Solubility (In Vitro)

DMSO : ~250 mg/mL (~575.45 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.79 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.79 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.3018 mL	11.5088 mL	23.0176 mL
	5 mM	0.4604 mL	2.3018 mL	4.6035 mL
	10 mM	0.2302 mL	1.1509 mL	2.3018 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.