PhTx-74 HCl (Philanthotoxin 74; PhTx 74; PhTx74), the dihydrochloride salt of PhTx-74, is an analogue of philanthotoxin-4,3,3 which is a naturally-occurring wasp venom toxin. PhTx-74 is a novel and potent AMPAR antagonist that inhibits GluR3 and GluR1 with IC50 values of 263 and 296 nM, respectively.

Physicochemical Properties

Molecular Formula	C24H44CL2N4O3
Molecular Weight	507.54
Exact Mass	506.279
Elemental Analysis	C, 56.80; H, 8.74; Cl, 13.97; N, 11.04; O, 9.46
CAS #	1227301-51-0
Related CAS #	401601-11-4;1227301-51-0 (HCl);
PubChem CID	46213501
Appearance	White to light yellow solid powder
Hydrogen Bond Donor Count	7
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	18
Heavy Atom Count	33
Complexity	468
Defined Atom Stereocenter Count	1
SMILES	O=C(NCCCCCCCNCCCCN)[C@@H](NC(CCC)=O)CC1=CC=C(O)C=C1.[H]Cl.[H]Cl
InChi Key	HWTJQQMIKVJWLH-IKXQUJFKSA-N
InChi Code	InChI=1S/C24H42N4O3.2ClH/c1-2-10-23(30)28-22(19-20-11-13-21(29)14-12-20)24(31)27-18-8-5-3-4-7-16-26-17-9-6-15-25/h11-14,22,26,29H,2-10,15-19,25H2,1H3,(H,27,31)(H,28,30)2*1H/t22-/m0../s1
Chemical Name	(S)-N-(1-((7-((4-aminobutyl)amino)heptyl)amino)-3-(4-hydroxyphenyl)-1-oxopropan-2-yl)butyramide dihydrochloride
Synonyms	PhTx 74PhTx74 Philanthotoxin 74 Philanthotoxin74 Philanthotoxin-74 HCl
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 Vitro	When oocytes coexpressed γ-2 with the two primary isoforms of GluA2R-containing AMPARs (GluA1/A2R and GluA2R/A3), philanthotoxin 74 exhibited selective inhibition in the micromolar dose range. At 500 μM, philanthotoxin 74 has been shown to totally inhibit GluA1/A2R receptors while just slightly inhibiting GluA2R/A3 receptors (10%). When tested at 100 and 500 μM concentrations, philanthotoxin 74 demonstrated negligible channel blocking of GluA2R/A3, but significant channel blocking of GluA1/A2R (greater than 80%). When evaluated at the highest dose of 300 μM, oocytes expressing GluA2R alone or homopolymeric GluA2R showed less than 5% inhibition, making them essentially inert to Zanthoxylin 74 in the concentration range of 0.1-300 μM. With an IC50 value of roughly 30 μM, philanthotoxin 74 non-selectively inhibits these receptors both in the presence and absence of gamma-2 [1].
References	[1]. Evaluation of PhTX-74 as subtype-selective inhibitor of GluA2-containing AMPA receptors. Mol Pharmacol. 2014 Feb;85(2):261-8. [2]. Solid-phase synthesis of polyamine toxin analogues: potent and selective antagonists of Ca2+-permeable AMPA receptors. J Med Chem. 2002 Dec 19;45(26):5745-54.
Additional Infomation	Philanthotoxin 74 is a tyrosine derivative.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~197.03 mM) H2O : ~50 mg/mL (~98.51 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (4.93 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 25.0 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: ≥ 2.5 mg/mL (4.93 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 25.0 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: ≥ 2.5 mg/mL (4.93 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 50 mg/mL (98.51 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.9703 mL	9.8514 mL	19.7029 mL
	5 mM	0.3941 mL	1.9703 mL	3.9406 mL
	10 mM	0.1970 mL	0.9851 mL	1.9703 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.