(±)-Fabesetron hydrochloride (FK-1052), the racemic mixture of Fabesetron, 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	C18H20CLN3O
Molecular Weight	329.823903083801
Exact Mass	329.129
CAS #	129299-81-6
Related CAS #	129299-81-6 ((±)-FK1052 HCl) 129300-27-2
PubChem CID	9949384
Appearance	Typically exists as solid at room temperature
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	2
Rotatable Bond Count	2
Heavy Atom Count	23
Complexity	440
Defined Atom Stereocenter Count	0
SMILES	O=C1C(CC2=C(C)N=CN2)CCC(N31)=C(C)C4=C3C=CC=C4.[H]Cl
InChi Key	POKFYJWUPWZYQV-UHFFFAOYSA-N
InChi Code	InChI=1S/C18H19N3O.ClH/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);1H
Chemical Name	10-methyl-7-[(5-methyl-1H-imidazol-4-yl)methyl]-8,9-dihydro-7H-pyrido[1,2-a]indol-6-one;hydrochloride
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

Both 5-HT and 5-methoxytryptamine markedly enhanced intestinal transit and fecal pellet excretion in awake rats. On the other hand, 2-methyl-5-HT has a negligible effect. While 5-HT (1 mg/kg sc)-stimulated colonic transit was marginally reduced by Ondansetron and Granisetron, the increase in colonic transit was totally suppressed by (±)-Fabesetron, 0.1 mg/kg po. Furthermore, the administration of (±)-fabesetron, ondansetron, and granisetron, with corresponding ED50 values of 0.21, 3.0, and 1.1 mg/kg po, significantly reduced the increase in fecal pellet excretion resulting from wrapping restraint stress. In fasting mice, intraperitoneal injection of 5-HT and 5-methoxytryptamine (but not 2-methyl-5-HT) increased the incidence of diarrhea in a dose-dependent manner. Additionally, 5-HT (0.32 mg/kg ip)-induced diarrhea is inhibited by (±)-Fabesetron, ondansetron, and granisetron, with corresponding ED50 values of 0.09, 2.3, and 0.88 mg/kg po [ 1]. (±)-Fabesetron (1 mg/kg iv ×4) raised the time to vomiting onset, albeit not significantly, and significantly decreased methotrexate (MTX)-induced delayed vomiting. Furthermore, it was found that administering 3.2 mg/kg of (±)-fabesetron was considerably less effective than giving 1 mg/kg of the drug in preventing MTX-induced vomiting [2].

References

[1]. Kadowaki M, 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]. Yamakuni H, et al. Probable involvement of the 5-hydroxytryptamine(4) receptor in methotrexate-induced delayed emesis in dogs. J Pharmacol Exp Ther. 2000 Mar;292(3):1002-7

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	3.0320 mL	15.1598 mL	30.3196 mL
	5 mM	0.6064 mL	3.0320 mL	6.0639 mL
	10 mM	0.3032 mL	1.5160 mL	3.0320 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.