Topoisomerase I inhibitor 17 (Compound 7h) is a Topoisomerase I (Top1) inhibitor. Topoisomerase I inhibitor 17 reduces DDX5 and reverses the locking of Top1 activity by DDX5. Topoisomerase I inhibitor 17 induces Top1-mediated DNA damage and promotes reactive oxygen species (ROS) production. Topoisomerase I inhibitor 17 induces apoptosis (reduced anti-apoptotic proteins XIAP, Bcl-2, Survivin and increased pro-apoptotic proteins Bax, γH2AX). Topoisomerase I inhibitor 17 also prevents the progression of the G2/M checkpoint and induces cell cycle arrest. Topoisomerase I inhibitor 17 significantly inhibits the ability of colorectal cancer cells to form colonies and migrate. Topoisomerase I inhibitor 17 effectively reduces tumors in mice bearing human PDX tumors.

Physicochemical Properties

Molecular Formula	C28H21FN2O7
Molecular Weight	516.47
CAS #	2413582-45-1
Appearance	Typically exists as solids at room temperature
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

Targets	Bax Bcl-2 Top1 XIAP
ln Vitro	Topoisomerase I inhibitor 17 (5-500 nM, 72 h) has antiproliferative effects on four cancer cells (HepG2, A549, HeLa and HCT116) with IC50 values of 136.6, 33.7, 72.9 and 36.1 nM, respectively[1]. Topoisomerase I inhibitor 17 can cross the Caco-2 cell monolayer with an apparent permeability coefficient of 2.24 μcm/s from the apical to the basolateral side (0.5-1.0 μM, 4 h), and the survival rate of Caco-2 cells is over 90% (0.2-1.0 μM, 4 h)[1]. Topoisomerase I inhibitor 17 (5-100 nM, 12-72 h) significantly inhibited proliferation-induced colony formation, concentration-dependently inhibited HCT116 cell migration, and increased ROS generation [1]. Topoisomerase I inhibitor 17 (0-50 μM, 48 h) induces apoptosis and cell cycle arrest in HCT116 cells in a dose-dependent manner, preventing progression of the G2/M checkpoint [1]. Topoisomerase I inhibitor 17 inhibits DDX5 expression in HCT116 cells (100 μM, 48-72 h) and relieves DDX5-blocked Top1 activity (5 and 50 μM)[1].
ln Vivo	Topoisomerase I inhibitor 17 (2-15 mg/kg, ip, once a week for 4 weeks) effectively reduces tumors in mice bearing human colon cancer PDX tumors through a concentration-dependent tumor inhibition effect and acceptable toxicity [1].
Cell Assay	Cell Cycle Analysis[1] Cell Types: HCT116 Tested Tested Concentrations: 0, 2.5, 10, 50 nM Incubation Duration: 48 h Experimental Results: Halted the progression of the G2/M checkpoint, Experimental Experimental Resultsed in a significant accumulation of cells at this critical pre-division stage, with increases in cell number observed at G2/M phases of 2.05% (0 nM), 33.48% (2.5 nM), 55.28% (5 nM) and 64.01% (10 nM), respectively. Apoptosis Analysis[1] Cell Types: HCT116 Tested Tested Concentrations: 50, 100 nM Incubation Duration: 72 h Experimental Results: Reduced expression of anti-apoptotic proteins (e.g. Survivin). Upregulated the pro-apoptotic proteins Bax and γH2AX in a dose-dependent manner.
Animal Protocol	Animal/Disease Models: FL118 colorectal cancer (CRC) patient-derived xenograft (PDX) tumors models using a limited number of severe combined immunodeficiency (SCID) mice[1] Doses: 2, 8 and 15 mg/kg Route of Administration: Intraperitoneal injection (i.p.) Experimental Results: Regressed CRC PDX27454 tumors after 21 days with no recurrence within 35 days through a concentration-dependent tumor-suppressive effect and acceptable toxicity at 15 mg/kg. Displayed stable mouse body weights.
References	[1]. Design, synthesis and investigation of biological activity and mechanism of fluoroaryl-substituted derivatives at the FL118 position 7. European journal of medicinal chemistry. 2024, 283, 117143.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

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	1.9362 mL	9.6811 mL	19.3622 mL
	5 mM	0.3872 mL	1.9362 mL	3.8724 mL
	10 mM	0.1936 mL	0.9681 mL	1.9362 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.