Sograzepide (Netazepide; YF 476; YM-220) is a very potent, selective and orally bioactive Gastrin/CCK-B antagonist (inhibitor) with IC50 of 0.1 nM. It also inhibits Gastrin/CCK-A activity with IC50 of 502 nM. Sograzepide (Netazepide; YF 476; YM-220) replaces [125I]CCK-8 and specifically binds to rat brain, cloned dog, and human Gastrin/CCK-B with Kis of 0.068, 0.62, and 0.19 nM, respectively.

Physicochemical Properties

Molecular Formula	C28H30N6O3
Molecular Weight	498.587
Exact Mass	498.238
CAS #	155488-25-8
Related CAS #	(Rac)-Sograzepide;168161-71-5
PubChem CID	9870520
Appearance	Off-white to light yellow solid powder
Density	1.25g/cm3
Boiling Point	723.049ºC at 760 mmHg
Flash Point	391.086ºC
LogP	4.048
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	7
Heavy Atom Count	37
Complexity	868
Defined Atom Stereocenter Count	1
SMILES	CC(C)(C)C(=O)CN1C2=CC=CC=C2C(=N[C@H](C1=O)NC(=O)NC3=CC=CC(=C3)NC)C4=CC=CC=N4
InChi Key	YDZYKNJZCVIKPP-VWLOTQADSA-N
InChi Code	InChI=1S/C28H30N6O3/c1-28(2,3)23(35)17-34-22-14-6-5-12-20(22)24(21-13-7-8-15-30-21)32-25(26(34)36)33-27(37)31-19-11-9-10-18(16-19)29-4/h5-16,25,29H,17H2,1-4H3,(H2,31,33,37)/t25-/m0/s1
Chemical Name	1-[(3R)-1-(3,3-dimethyl-2-oxobutyl)-2-oxo-5-pyridin-2-yl-3H-1,4-benzodiazepin-3-yl]-3-[3-(methylamino)phenyl]urea
Synonyms	YF 476; YF-476; YF476
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

Anesthetized rats' stomach acid secretion induced by pentagastrin is inhibited by sograzepide (Netazepide; YF 476; YM-220) (0.1 μmol/kg; intravenous injection), with an ED50 of 87 nmol/kg[1]. With an ED50 value of 0.0086 μM/kg, sograzepide (Netazepide; YF 476; YM-220) (intravenous injection; 10 μM/kg) reduces pentagastrin-induced acid secretion but has no effect on histamine or bethanechol. acid secretion brought on by bases [2]. With ED50 values of 0.018 and 0.020 μM/kg, sograzepide (Netazepide; YF 476; YM-220) (IV; PO) suppresses pentagastrin-stimulated stomach acid secretion in a dose-dependent manner in Heidenhain pouch dogs [2].

References

[1]. Effect of netazepide, a gastrin/CCK2 receptor antagonist, on gastric acid secretion and rabeprazole-induced hypergastrinaemia in healthy subjects. Br J Clin Pharmacol. 2015 May;79(5):744-55. [2]. YF476 is a new potent and selective gastrin/cholecystokinin-B receptor antagonist in vitro and in vivo.Aliment Pharmacol Ther. 1997 Feb;11(1):113-20.

Solubility Data

Solubility (In Vitro)

DMSO : ≥ 100 mg/mL (~200.57 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.17 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.17 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 3: ≥ 2.08 mg/mL (4.17 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.0057 mL	10.0283 mL	20.0566 mL
	5 mM	0.4011 mL	2.0057 mL	4.0113 mL
	10 mM	0.2006 mL	1.0028 mL	2.0057 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.