Zoniporide (CP-597396) HCl hydrate is a novel highly potent and specific inhibitor of sodium-hydrogen exchanger type 1 (NHE-1) with cardioprotective effects against myocardial injuries and ischemic insults. Zoniporide HCl hydrate inhibits human NHE-1 (IC50=14 nM), and has >150-fold selectivity versus other NHE isoforms. Zoniporide HCl hydrate highly potently inhibits ex vivo NHE-1-dependent swelling of human platelets (IC50=59 nM).

Physicochemical Properties

Molecular Formula	C₁₇H₁₉CLN₆O₂
Molecular Weight	374.82
Exact Mass	374.126
CAS #	863406-85-3
Related CAS #	Zoniporide hydrochloride;241800-97-5
PubChem CID	22267662
Appearance	White to off-white solid powder
LogP	4.033
Hydrogen Bond Donor Count	4
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	3
Heavy Atom Count	26
Complexity	515
Defined Atom Stereocenter Count	0
InChi Key	UCIJUEGJEFJRMP-UHFFFAOYSA-N
InChi Code	InChI=1S/C17H16N6O.ClH.H2O/c18-17(19)22-16(24)12-9-21-23(15(12)10-6-7-10)14-5-1-4-13-11(14)3-2-8-20-13;;/h1-5,8-10H,6-7H2,(H4,18,19,22,24);1H;1H2
Chemical Name	5-cyclopropyl-N-(diaminomethylidene)-1-quinolin-5-ylpyrazole-4-carboxamide;hydrate;hydrochloride
Synonyms	CP597396 CP-597396CP 597396
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, 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 Vivo	Zonipol hydrochloride hydrate (0.25-4 mg/kg; intravenously; once hourly for 2 hours) causes a dose-dependent reduction in infarct size in rabbits under thoracotomy anesthesia (ED50=0.45 mg/kg/ h)[1]. Zoniporide exhibits moderate plasma protein binding with a t1/2 of 1.5 hours in monkeys and has one major active metabolite [1]. Zonipol hydrochloride hydrate treatment showed AUC0-∞ and t1/2 of 0.07 μg·h/mL and 0.5 hours respectively [2].
Animal Protocol	Animal/Disease Models: Rabbit [1] Doses: 0.25, 1, 4 mg/kg Route of Administration: once every hour for 2 hrs (hrs (hours)); intravenous (iv) (iv)injection Experimental Results: There was a significant dose-dependent reduction in infarct area in anesthetized rabbits. ED50 is 0.45 mg/kg/h. Animal/Disease Models: Rat [2] Doses: 1 mg/kg Route of Administration: intravenous (iv) (iv)injection (pharmacokinetic/PK/PK analysis) Experimental Results: AUC0-∞ and t1/2 were 0.07 μg·h/mL and 0.5 hrs (hrs (hours)) respectively.
References	[1]. Zoniporide: a potent and selective inhibitor of the human sodium-hydrogen exchanger isoform 1 (NHE-1). Cardiovasc Drug Rev. 2003 Spring;21(1):17-32. [2]. Discovery of zoniporide: a potent and selective sodium-hydrogen exchanger type 1 (NHE-1) inhibitor with high aqueous solubility. Bioorg Med Chem Lett. 2001 Mar 26;11(6):803-7.

Solubility Data

Solubility (In Vitro)

H2O : ~2 mg/mL (~5.34 mM)

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	2.6679 mL	13.3397 mL	26.6795 mL
	5 mM	0.5336 mL	2.6679 mL	5.3359 mL
	10 mM	0.2668 mL	1.3340 mL	2.6679 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.