HUHS015 is a novel and potent inhibitor of PCA-1/ALKBH3 (prostate cancer antigen-1/AlkB Homolog 3) both in vitro and in vivo that was discovered from the optimization of a hit compound identified during random screening using a recombinant PCA-1/ALKBH3. The bioavailability (BA) of HUHS015 was 7.2% in rats after oral administration. Continuously administering HUHS015 significantly suppressed the growth of DU145 cells, which are human hormone-independent prostate cancer cells, in a mouse xenograft model without untoward effects.

Physicochemical Properties

Molecular Formula	C19H18N4O
Molecular Weight	318.37
Exact Mass	318.148
CAS #	1453097-13-6
Related CAS #	1453097-13-6
PubChem CID	71696702
Appearance	White to off-white solid powder
Density	1.3±0.1 g/cm3
Boiling Point	585.2±42.0 °C at 760 mmHg
Flash Point	307.7±27.9 °C
Vapour Pressure	0.0±1.7 mmHg at 25°C
Index of Refraction	1.689
LogP	4.72
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	3
Heavy Atom Count	24
Complexity	526
Defined Atom Stereocenter Count	0
SMILES	OC1=C(CC2=CC=CC=C2)C(C)=NN1C3=NC4=CC=C(C)C=C4N3
InChi Key	IQOKQFQFGHZHJT-UHFFFAOYSA-N
InChi Code	InChI=1S/C19H18N4O/c1-12-8-9-16-17(10-12)21-19(20-16)23-18(24)15(13(2)22-23)11-14-6-4-3-5-7-14/h3-10,22H,11H2,1-2H3,(H,20,21)
Chemical Name	4-benzyl-5-methyl-2-(6-methyl-1H-benzimidazol-2-yl)-1H-pyrazol-3-one
Synonyms	HUHS015; HUHS 015; HUHS-015
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	Human hormone-independent prostate cancer cells, or DU145 cells, are greatly suppressed in growth by HUHS015[1].
ln Vivo	DU145 cell growth is potently suppressed by HUHS015 in a mouse xenograft model[1]. After oral administration, HUHS015 exhibits a 7.2% bioavailability (BA) in rats[1].
Animal Protocol	Animal/Disease Models: Nude mice[1] Doses: 32 mg/kg Route of Administration: subcutaneous (sc) injection; daily; 6 days Experimental Results: Has inhibitory effect on the growth of subcutaneously (sc) implanted DU145, without limiting weight gains after a 6 days continuous administration.
References	[1]. Nakao S et al. Design and synthesis of prostate cancer antigen-1 (PCA-1/ALKBH3) inhibitors as anti-prostate cancer drugs. Bioorg Med Chem Lett, 2014 Feb 15, 24(4):1071-4.

Solubility Data

Solubility (In Vitro)

DMSO:≥ 34 mg/mL Water:<1 mg/mL Ethanol:

Solubility (In Vivo)

Solubility in Formulation 1: 2.5 mg/mL (7.85 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. 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 2: ≥ 2.5 mg/mL (7.85 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 3: 5 mg/mL (15.70 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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	3.1410 mL	15.7050 mL	31.4100 mL
	5 mM	0.6282 mL	3.1410 mL	6.2820 mL
	10 mM	0.3141 mL	1.5705 mL	3.1410 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.