Fabesetron (FK1052) is a novel, potent and orally bioactive 5-HT3 receptor antagonist with 5-HT4 receptor antagonistic activity. It has the potential to be used in treating acute and delayed emesis induced by cancer chemotherapy.

Physicochemical Properties

Molecular Formula	C₁₈H₁₉N₃O
Molecular Weight	293.36
Exact Mass	293.153
CAS #	129300-27-2
Related CAS #	129299-81-6 ((±)-FK1052 HCl)
PubChem CID	208947
Appearance	Off-white to light yellow solid powder
Vapour Pressure	1.28E-12mmHg at 25°C
LogP	3.426
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	2
Rotatable Bond Count	2
Heavy Atom Count	22
Complexity	440
Defined Atom Stereocenter Count	1
SMILES	CC1NC=NC=1C[C@H]1CCC2N(C3=CC=CC=C3C=2C)C1=O
InChi Key	AEKQMJRJRAHOAP-CYBMUJFWSA-N
InChi Code	InChI=1S/C18H19N3O/c1-11-14-5-3-4-6-17(14)21-16(11)8-7-13(18(21)22)9-15-12(2)19-10-20-15/h3-6,10,13H,7-9H2,1-2H3,(H,19,20)/t13-/m1/s1
Chemical Name	(7R)-10-methyl-7-[(5-methyl-1H-imidazol-4-yl)methyl]-8,9-dihydro-7H-pyrido[1,2-a]indol-6-one
Synonyms	FK1052 FK-1052 FK 1052
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 Vivo	Fabesetron (FK1052) (0.1 mg/kg po) totally prevents the rise in intestinal transit [1]. FK1052 (100 µg/kg) totally eliminates cisplatin (18 mg/kg, ip)-induced vomiting in Suncus murinus [2].
Animal Protocol	Animal/Disease Models: Male SD (SD (Sprague-Dawley)) rats weighing 220 to 330 grams and male ddy mice weighing 25 to 35 grams were used [1]. Doses: 0.1 mg/kg. Route of Administration: PO Experimental Results: 0.1 mg/kg po caused significant delay with a degree of inhibition of 33.8 ± 4.8%. Animal/Disease Models: Suncus murinus of either gender (>10 weeks old; body weight 30-70 grams) [2]. Doses: 1, 10 and 100 µg/kg. Route of Administration: Take orally 30 minutes before injecting cisplatin. Experimental Results: Cisplatin-induced vomiting was inhibited in a dose-dependent manner, with no vomiting observed in the three animals administered 100 µg/kg of compound.
References	[1]. M Kadowaki, et al. Effect of FK1052, a potent 5-hydroxytryptamine3 and 5-hydroxytryptamine4 receptor dual antagonist, on colonic function in vivo. J Pharmacol Exp Ther. 1993 Jul;266(1):74-80. [2]. Hiroe Nakayama, et al. Antiemetic activity of FK1052, a 5-HT3- and 5-HT4-receptor antagonist, in Suncus murinus and ferrets. J Pharmacol Sci. 2005 Aug;98(4):396-403.
Additional Infomation	Fabesetron is an organic heterotricyclic compound that is 8,9-dihydropyrido[1,2-a]indol-6(7H)-one substituted by a (5-methyl-1H-imidazol-4-yl)methyl group at position 7R and a methyl group at position 10. It is a dual 5-HT3 and 5-HT4 receptors antagonist whose clinical development was terminated in phase II. It was being developed for the treatment of chemotherapy-induced emesis and irritable bowel syndrome. It has a role as an antiemetic and a serotonergic antagonist. It is a member of imidazoles and an organic heterotricyclic compound.

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	3.4088 mL	17.0439 mL	34.0878 mL
	5 mM	0.6818 mL	3.4088 mL	6.8176 mL
	10 mM	0.3409 mL	1.7044 mL	3.4088 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.