NSC77674 (also known as PIH or Pyridoxal isonicotinoyl hydrazone) is is a novel, potent, lipophilic, nontoxic, iron-chelating agent that shows high iron chelation efficacy both in vitro in cell culture models and in vivo in rats and mice. As iron is a crucial component of metabolic pathways involved in DNA synthesis, cancerous cells have a high iron requirement due to rapid rates of proliferation. While pyridoxal isonicotinoyl hydrazine exhibits low anticancer activity, its analogs demonstrate antiproliferative effects in a range of tumor cells. As a cell-permeable, non-toxic tridendate iron (Fe3+) chelator of the aroyl hydrazone class, even at low concentrations, NSC77674 is highly effective in mobilizing Fe3+ from cells and preventing its uptake from transferrin. It exhibits similar specificity and binding affinity as Deferoxamine Mesylate but has greater access to mitochondrial iron. It is also useful for the management of iron overload disease in experimental models.

Physicochemical Properties

Molecular Formula	C14H14N4O3
Molecular Weight	286.28596
Exact Mass	286.107
Elemental Analysis	C, 58.74; H, 4.93; N, 19.57; O, 16.77
CAS #	737-86-0
PubChem CID	135409539
Appearance	Light yellow to yellow solid powder
Density	1.35g/cm3
Index of Refraction	1.646
LogP	1.137
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	4
Heavy Atom Count	21
Complexity	371
Defined Atom Stereocenter Count	0
SMILES	CC1=NC=C(C(=C1O)C=NNC(=O)C2=CC=NC=C2)CO
InChi Key	BQYIXOPJPLGCRZ-REZTVBANSA-N
InChi Code	InChI=1S/C14H14N4O3/c1-9-13(20)12(11(8-19)6-16-9)7-17-18-14(21)10-2-4-15-5-3-10/h2-7,19-20H,8H2,1H3,(H,18,21)/b17-7+
Chemical Name	N-[(E)-[3-hydroxy-5-(hydroxymethyl)-2-methylpyridin-4-yl]methylideneamino]pyridine-4-carboxamide
Synonyms	NSC 77674; NSC-77674; NSC77674; PIH; Pyridoxal isonicotinoyl hydrazone;
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: This product requires protection from light (avoid light exposure) during transportation and storage.
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

References

Molecular Pharmacology78(4),675-684(2010);J Lab Clin Med. 1998 Apr;131(4):306-15.

Solubility Data

Solubility (In Vitro)

DMSO : ~14.71 mg/mL (~51.38 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 1.47 mg/mL (5.13 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 14.7 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: ≥ 1.47 mg/mL (5.13 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 14.7 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 3: 1.47 mg/mL (5.13 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 14.7 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	3.4930 mL	17.4648 mL	34.9296 mL
	5 mM	0.6986 mL	3.4930 mL	6.9859 mL
	10 mM	0.3493 mL	1.7465 mL	3.4930 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.