SMI-16a (Pim1/2 Inhibitor IV) is a novel, potent, selective, cell-permeable, ATP-competitive Pim kinase inhibitor with IC50 values of 0.15, 0.02 and 48 μM for Pim1, Pim2 and PC3 cells, respectively. The Pim protein kinases are frequently overexpressed in prostate cancer and certain forms of leukemia and lymphoma. SMI-16a was identified by screening to be a Pim-1 inhibitor and was found to attenuate the autophosphorylation of tagged Pim-1 in intact cells. Although SMI-16a is a competitive inhibitor with respect to ATP, a screen of approximately 50 diverse protein kinases demonstrated that it has high selectivity for Pim kinases. SMI-16a demonstrated selectivities of more than 2500-fold and 400-fold for Pim-1 or Pim-2, respectively. Overall, SMI-16a has the potential to be developed into a novel anticancer agent.

Physicochemical Properties

Molecular Formula	C13H13NO3S
Molecular Weight	263.31222
Exact Mass	263.061
CAS #	587852-28-6
Related CAS #	587852-28-6
PubChem CID	6076476
Appearance	Light yellow to yellow solid powder
LogP	3.1
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	4
Heavy Atom Count	18
Complexity	359
Defined Atom Stereocenter Count	0
SMILES	O=C(NC/1=O)SC1=C\C2=CC=C(OCCC)C=C2
InChi Key	GBWOSXZUTXXXQF-FLIBITNWSA-N
InChi Code	InChI=1S/C13H13NO3S/c1-2-7-17-10-5-3-9(4-6-10)8-11-12(15)14-13(16)18-11/h3-6,8H,2,7H2,1H3,(H,14,15,16)/b11-8-
Chemical Name	(Z)-5-(4-Propoxybenzylidene)thiazolidine-2,4-dione
Synonyms	SMI-16a; SMI16a; SMI 16a; Pim1/2 Inhibitor IV; PIM1/2 Kinase Inhibitor VI; Pim1/2 Kinase Inhibitor IV;
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	SMI-16a exhibits superior inhibitory properties against Pim-1 and Pim-2 [1]. In MM cells, treatment with Pim-2 short interfering RNA and the Pim inhibitor SMI-16a effectively restored osteoblastogenesis, which had been suppressed by all of the aforementioned inhibitors. Treatment with SMI-16a increases anabolic signaling mediated by BMP-2 and inhibits TGF-β signaling [2].
ln Vivo	SMI-16a was administered intraperitoneally to mice at a dose of 50 mg/kg every day for five days; a dose of 100 mg/kg was markedly hazardous. Five days a week of SMI-16a treatment decreased tumor growth in the mice by around 50% without resulting in weight loss. Red blood cell and white blood cell counts (including lymphocytes, monocytes, and granulocytes) were unaffected by subchronic treatment of SMI-16a, suggesting that the substance has no myelosuppressive effects. Because albumin, alkaline phosphatase, and alanine aminotransferase levels remain unchanged, SMI-16a is not hepatotoxic [1]. SMI-16a can successfully stop bone deterioration while preventing MM tumor growth in animal models of MM [2].
Animal Protocol	50 mg/kg; i.p. Female Balb/C mice injected subcutaneously with JC cells suspended in PBS
References	[1]. Synthesis and evaluation of novel inhibitors of Pim-1 and Pim-2 protein kinases. J Med Chem. 2009 Jan 8;52(1):74-86. [2]. Pim-2 kinase is an important target of treatment for tumor progression and bone loss in myeloma. Leukemia. 2015 Jan;29(1):207-17.

Solubility Data

Solubility (In Vitro)

DMSO:≥ 150mg/mL Water:N/A Ethanol:N/A

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (9.49 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 (9.49 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 (9.49 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	3.7978 mL	18.9890 mL	37.9780 mL
	5 mM	0.7596 mL	3.7978 mL	7.5956 mL
	10 mM	0.3798 mL	1.8989 mL	3.7978 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.