SMIP004 also known as N-(4-butyl-2-methyl-phenyl) is a novel specific inducer of cancer-cell-specific apoptosis in human prostate cancer cells. Positive cell cycle regulators were downregulated by SMIP004, while cyclin-dependent kinase inhibitors were upregulated. These changes led to G1 arrest, the prevention of soft agar colony formation, and cell death. However, it was still unclear how SMIP004 caused cancer cells to selectively undergo apoptosis. Prostate and breast cancer xenografts in mice are potently inhibited by SMIP004. Our findings indicate that SMIP004 targets specific redox and bioenergetic sensitivities of prostate cancer cells that can be used as a therapeutic target by causing the production of mitochondrial ROS.

Physicochemical Properties

Molecular Formula	C13H19NO
Molecular Weight	205.3
Exact Mass	205.147
Elemental Analysis	C, 76.06; H, 9.33; N, 6.82; O, 7.79
CAS #	143360-00-3
Related CAS #	143360-00-3
PubChem CID	2747581
Appearance	White to off-white solid powder
Density	1.003g/cm3
Boiling Point	343ºC at 760mmHg
Flash Point	206.1ºC
Vapour Pressure	7.24E-05mmHg at 25°C
Index of Refraction	1.539
LogP	3.369
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	1
Rotatable Bond Count	4
Heavy Atom Count	15
Complexity	203
Defined Atom Stereocenter Count	0
SMILES	CC1=C(NC(C)=O)C=CC(CCCC)=C1
InChi Key	ZFVMECVBUGMWIX-UHFFFAOYSA-N
InChi Code	InChI=1S/C13H19NO/c1-4-5-6-12-7-8-13(10(2)9-12)14-11(3)15/h7-9H,4-6H2,1-3H3,(H,14,15)
Chemical Name	N-(4-butyl-2-methylphenyl)acetamide
Synonyms	SMIP004; SMIP-004; SMIP 004
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

Targets	SKP2 E3 ligase
ln Vitro	SMIP004, a N-(4-butyl-2-methyl-phenyl) acetamide, is a novel specific inducer of cancer-cell selective apoptosis of human prostate cancer cells. SMIP004 decreased the levels of positive cell cycle regulators, upregulated cyclin-dependent kinase inhibitors, and resulted in G1 arrest, inhibition of colony formation in soft agar, and cell death. However, the mechanism of SMIP004-induced cancer cell selective apoptosis remained unknown. SMIP004 potently inhibits the growth of prostate and breast cancer xenografts in mice. Our data suggest that SMIP004, by inducing mitochondrial ROS formation, targets specific sensitivities of prostate cancer cells to redox and bioenergetic imbalances that can be exploited in cancer therapy.
ln Vivo	SMIP004 potently inhibits the growth of prostate and breast cancer xenografts in mice.
Enzyme Assay	SMIP004 also known as N-(4-butyl-2-methyl-phenyl) is a novel specific inducer of cancer-cell-specific apoptosis of human prostate cancer cells.
Cell Assay	Whereas SMIP012 and 016 were moderately toxic in normal fibroblasts, SMIPs 001 and 004 showed substantial cancer cell specificity being at least five times more potent in LNCaP-S14 than in IMR90 cells , treatment with either MG132 or SMIP004 increased p27 half-life to > 6 h. SMIP004 also decreased the quantities of cyclins E and A obtained using CDK2. Cyclins E and A significantly decreased after receiving SMIP004 treatment, which was paralleled by this. Positive cell cycle regulators were downregulated by SMIP004, cyclin-dependent kinase inhibitors were upregulated, G1 arrest, soft agar colony formation was inhibited, and cell death occurred.
Animal Protocol	Mice with prostate and breast cancer xenografts
References	[1]. J Exp Clin Cancer Res. 2019 Feb 13;38(1):76. [2]. Oncotarget. 2013 Aug;4(8):1212-29..
Additional Infomation	SMIP004 is a member of the class of N-benzylacetamides that is benzene substituted by acetylnitrilo, methyl, and butyl groups at positions 1, 2 and 4, respectively. It is a SKP2 E3 ligase inhibitor and a selective apoptosis inducer of human prostate cancer cells. It has a role as an antineoplastic agent, an apoptosis inducer, an antidepressant, an EC 6.3.2.19 (ubiquitin--protein ligase) inhibitor, an autophagy inducer and an anticoronaviral agent. It is a member of toluenes, a member of N-benzylacetamides and an alkylbenzene.

Solubility Data

Solubility (In Vitro)

DMSO: ~10 mM in DMSO Water: <1 mg/mL Ethanol: <1 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (12.18 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 2: ≥ 2.5 mg/mL (12.18 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	4.8709 mL	24.3546 mL	48.7092 mL
	5 mM	0.9742 mL	4.8709 mL	9.7418 mL
	10 mM	0.4871 mL	2.4355 mL	4.8709 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.