Fulvene-5 is a novel and highly potent inhibitor of NADPH oxidase 4 (NOX4) with antioxidant and anticancer activities. Fulvene-5 is a reactive oxygen species (ROS) modifying agent and a highly potent radioprotector.

Physicochemical Properties

Molecular Weight	358.434525966644
Exact Mass	358.146
CAS #	1075723-01-1
PubChem CID	156597123
Appearance	Typically exists as solid at room temperature
LogP	5.4
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	2
Rotatable Bond Count	0
Heavy Atom Count	28
Complexity	803
Defined Atom Stereocenter Count	0
InChi Key	SELCTRAHLFTCQL-UHFFFAOYSA-N
InChi Code	InChI=1S/C26H18N2/c1-2-10-17(9-1)23-19-13-5-7-15-21(19)27-25(23)26-24(18-11-3-4-12-18)20-14-6-8-16-22(20)28-26/h1-16,27-28H
Chemical Name	3-cyclopenta-2,4-dien-1-ylidene-2-(3-cyclopenta-2,4-dien-1-ylidene-1H-indol-2-ylidene)-1H-indole
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	Fulvene-5 (10 µM; 1 hour) facilitates the reversal of the adaptive response between pro-survival and radiosensitization in HCT116 TP53 wild-type (WT) and HCT116 isogenic TP53 null mutant (Mut) cell cultures. Naturally. Concurrent with these modifications, survivin translocation was reversed, moving from the cytoplasm of TP53 Mut cells to the nucleus of TP53 WT cells. Through the use of NOX4 siRNA oligomers to decrease NOX4 expression, HCT116 cells were used to study the possible involvement of NOX4 in the development of survivin-related adaptive responses. NOX4 expression is around 50% suppressed under these circumstances [1]. Treatment with Fulvene-5 (0.5-1.0 μM) in bEnd.3 cells decreases the expression of DLL4, Ang2, Nrarp, and placental growth factor (PLGF) in a dose-dependent manner [2].
ln Vivo	A two-week treatment of mice with hemangiomas naked with fulvene-5 (120 mg/kg/d; intraperitoneal injection; daily) can successfully limit the formation of these tumors [2].
Animal Protocol	Animal/Disease Models: Nude mice were injected with bEnd.3 cells [2]. Doses: 120 mg/kg/d. Route of Administration: intraperitoneal (ip) injection; daily; lasted for 2 weeks. Experimental Results: Tumor growth in mice was Dramatically diminished.
References	[1]. Murley JS, et al. ROS modifiers and NOX4 affect the expression of the survivin-associated radio-adaptive response. Free Radic Biol Med. 2018 Aug 1;123:39-52. [2]. Bhandarkar SS, et al. Fulvene-5 potently inhibits NADPH oxidase 4 and blocks the growth of endothelial tumors in mice. J Clin Invest. 2009 Aug;119(8):2359-65. [3]. Weyemi U, et al. Inactivation of NADPH oxidases NOX4 and NOX5 protects human primary fibroblasts from ionizing radiation-induced DNA damage. Radiat Res. 2015 Mar;183(3):262-70.

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	2.7899 mL	13.9497 mL	27.8995 mL
	5 mM	0.5580 mL	2.7899 mL	5.5799 mL
	10 mM	0.2790 mL	1.3950 mL	2.7899 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.