Duocarmycin SA is an orally bioactive anti-tumor antibiotic with IC50 of 10 pM. Duocarmycin SA is a very potent cytotoxic agent that induces sequence-selective alkylation of double-stranded DNA. Duocarmycin SA displays synergistic cell toxicity/cytotoxicity against glioblastoma multiforme (GBM) cells treated with proton irradiation in vitro.

Physicochemical Properties

Molecular Formula	C25H23N3O7
Molecular Weight	477.46600
Exact Mass	477.154
CAS #	130288-24-3
PubChem CID	115369
Appearance	Off-white to light yellow solid powder
Density	1.53±0.1 g/cm3
Vapour Pressure	8.82E-25mmHg at 25°C
LogP	2.74
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	6
Heavy Atom Count	35
Complexity	971
Defined Atom Stereocenter Count	2
SMILES	COC1=C(C(=C2C(=C1)C=C(N2)C(=O)N3C[C@H]4C[C@@]45C3=CC(=O)C6=C5C=C(N6)C(=O)OC)OC)OC
InChi Key	VQNATVDKACXKTF-XELLLNAOSA-N
InChi Code	InChI=1S/C25H23N3O7/c1-32-17-6-11-5-14(26-19(11)22(34-3)21(17)33-2)23(30)28-10-12-9-25(12)13-7-15(24(31)35-4)27-20(13)16(29)8-18(25)28/h5-8,12,26-27H,9-10H2,1-4H3/t12-,25-/m1/s1
Chemical Name	methyl (1R,12S)-7-oxo-10-(5,6,7-trimethoxy-1H-indole-2-carbonyl)-5,10-diazatetracyclo[7.4.0.01,12.02,6]trideca-2(6),3,8-triene-4-carboxylate
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 (e.g. under nitrogen), 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)

Biological Activity

ln Vitro	Duocarmycin SA (DSA) (0.1-1 nM; 72 hours) decreases U-138 cell pathway survival in a dose-dependent manner and activates insets and endpoints [2]. Duocarmycin SA (0.1-1 nM; 72 hours) flow chart.
ln Vivo	In CDF1 mice implanted with mouse liver cancer P388, duocarmycin SA (0.143 mg/kg, intraperitoneal injection, single dose) shown anti-tumor efficacy, considerably prolonging carotene in mice by 30% [3]. Mice lacking CDF1 were given a transplant of murine lymphocytic leukemia P388 [3].
Cell Assay	Cell viability assay [1] Cell Types: U-138 Cell Tested Concentrations: 0.1, 0.5, 1 nM Incubation Duration: 72 hrs (hours) Experimental Results: Produced a significant concentration-dependent decrease in cell viability, and tumor cells were more sensitive to proton radiation [2]. 65% cell viability was observed at 0.1 nM, cell viability stabilized at at least 25% at 0.5 nM, and no increase in cytotoxicity was observed at higher doses. The IC50 of Duocarmycin SA against U-138 MG cells is 0.4 nM. Exhibits strong cytotoxicity with an IC50 of 0.0018 nM (1.8 pM). Apoptosis analysis [1] Cell Types: U-138 Cell Tested Concentrations: 0.001, 0.1 nM Incubation Duration: 3 or 14 days Experimental Results: Improved radiosensitivity of U-138 GBM cells by activating apoptosis and necrosis pathways. Survival rates were Dramatically diminished at different proton radiation doses (1-8 Gy).
Animal Protocol	Animal/Disease Models: Murine lymphocytic leukemia P388 transplanted in CDF1 mice [3] Doses: 0.143 mg/kg Route of Administration: intraperitoneal (ip) injection (i.p.), single dose Experimental Results:demonstrated a significant 30% increase in life span.
References	[1]. Synthesis and evaluation of a thio analogue of duocarmycin SA. Bioorg Med Chem Lett. 2009 Dec 15;19(24):6962-5. [2]. Boyle KE, et.al. Duocarmycin SA, a potent antitumor antibiotic, sensitizes glioblastoma cells to proton radiation. Bioorg Med Chem Lett. 2018 Sep 1;28(16):2688-2692. [3]. Ichimura M,et.al. Duocarmycin SA, a new antitumor antibiotic from Streptomyces sp. J Antibiot (Tokyo). 1990 Aug;43(8):1037-8.
Additional Infomation	Duocarmycin SA is an indolecarboxamide. Duocarmycin sa has been reported in Streptomyces with data available.

Solubility Data

Solubility (In Vitro)

DMSO : ~50 mg/mL (~104.72 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 5 mg/mL (10.47 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 50.0 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: ≥ 5 mg/mL (10.47 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 50.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.0944 mL	10.4719 mL	20.9437 mL
	5 mM	0.4189 mL	2.0944 mL	4.1887 mL
	10 mM	0.2094 mL	1.0472 mL	2.0944 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.