AS8351 is a potent inhibitor of KDM5B (lysine-specific histone demethylase 5B) which plays an important role in maintaining cancer stem cells and justifies the rationale for studying the effects of continuous inhibition of this epigenetic factor in cancer. AS8351 can induce and sustain active chromatin marks to facilitate the induction of cardiomyocyte-like cells.It induces reprogramming of human fetal lung fibroblasts into functional cardiomyocytes, in combination with CHIR 99021, A83-01, BIX 01294, SC1, Y-27632, OAC2, SU 16f and JNJ 10198409. Reprogramming somatic fibroblasts into alternative lineages would provide a promising source of cells for regenerative therapy. However, transdifferentiating human cells into specific homogeneous, functional cell types is challenging.

Physicochemical Properties

Molecular Formula	C17H13N3O2
Molecular Weight	291.3
Exact Mass	291.101
Elemental Analysis	C, 70.09; H, 4.50; N, 14.42; O, 10.98
CAS #	796-42-9
Related CAS #	796-42-9
PubChem CID	135400486
Appearance	Light yellow to yellow solid powder
Density	1.364g/cm3
Boiling Point	503.5ºC at 760 mmHg
Melting Point	266 °C
Flash Point	258.3ºC
Index of Refraction	1.715
LogP	3.095
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	3
Heavy Atom Count	22
Complexity	407
Defined Atom Stereocenter Count	0
SMILES	O=C(C1C=CN=CC=1)NN=CC1C2C(=CC=CC=2)C=CC=1O
InChi Key	WQSHHAVECQJKLX-YBFXNURJSA-N
InChi Code	InChI=1S/C17H13N3O2/c21-16-6-5-12-3-1-2-4-14(12)15(16)11-19-20-17(22)13-7-9-18-10-8-13/h1-11,21H,(H,20,22)/b19-11+
Chemical Name	N-[(E)-(2-hydroxynaphthalen-1-yl)methylideneamino]pyridine-4-carboxamide
Synonyms	NSC51355;NSC 51355;NSC-51355; AS-8351; AS-8351; AS-8351
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 Vitro	By competing with α-ketoglutarate (α-KG) to chelate iron [Fe(II)] in specific epigenetic enzymes, like the JmjC-containing structure that needs α-KG and iron domain-based histone demethylase (JmjC-KDM) as a cofactor, AS8351 influences epigenetic modifications [2].
ln Vivo
Animal Protocol
References	[1]. Chemical Modulation of Cell Fate in Stem Cell Therapeutics and Regenerative Medicine. Cell Chem Biol. 2016 Aug 18;23(8):893-916. [2]. Conversion of human fibroblasts into functional cardiomyocytes by small molecules. Science. 2016 Jun 3;352(6290):1216-20.

Solubility Data

Solubility (In Vitro)

DMSO:150 mg/mL Water:<1 mg/mL Ethanol:<1 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (8.58 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.4329 mL	17.1644 mL	34.3289 mL
	5 mM	0.6866 mL	3.4329 mL	6.8658 mL
	10 mM	0.3433 mL	1.7164 mL	3.4329 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.