FLLL32, a synthetic curcumin analog, is a novel and potent Janus kinases-JAK2/STAT3 inhibitor with potential antitumor activity. It inhibits JAK2 with IC50 of<5 μM. FLLL-32 shows potent in vitro antiproliferative activity and high in vivo antitumor efficacy.

Physicochemical Properties

Molecular Formula	C28H32O6
Molecular Weight	464.55
Exact Mass	464.22
CAS #	1226895-15-3
Related CAS #	1226895-15-3
PubChem CID	68019246
Appearance	Light yellow to yellow solid powder
LogP	5.536
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	10
Heavy Atom Count	34
Complexity	668
Defined Atom Stereocenter Count	0
SMILES	COC1=C(C=C(C=C1)/C=C/C(=O)C2(CCCCC2)C(=O)/C=C/C3=CC(=C(C=C3)OC)OC)OC
InChi Key	NQDROBVIYYEMDQ-WFYKWJGLSA-N
InChi Code	InChI=1S/C28H32O6/c1-31-22-12-8-20(18-24(22)33-3)10-14-26(29)28(16-6-5-7-17-28)27(30)15-11-21-9-13-23(32-2)25(19-21)34-4/h8-15,18-19H,5-7,16-17H2,1-4H3/b14-10+,15-11+
Chemical Name	(E)-3-(3,4-dimethoxyphenyl)-1-[1-[(E)-3-(3,4-dimethoxyphenyl)prop-2-enoyl]cyclohexyl]prop-2-en-1-one
Synonyms	FLLL-32; FLLL32; FLLL 32
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

ln Vitro	In human melanoma cell lines and primary melanoma cultures, FLLL32 selectively decreases STAT3 phosphorylation at Tyr705 (pSTAT3) and promotes apoptosis at micromolar amounts[1].
ln Vivo	In MDA-MB-231 xenografted mice, FLLL32 (50 mg/kg, i.p.) significantly reduces tumor burdens. In mouse xenografts with OS-33 osteosarcoma cells, FLLL32 (50 mg/kg, i.p.) also inhibits tumor growth by targeting STAT3.
Animal Protocol	Dissolved in DMSO; 50 mg daily; i.p. injection MDA-MB-231 xenografted mice
References	[1]. The small molecule curcumin analog FLLL32 induces apoptosis in melanoma cells via STAT3inhibition and retains the cellular response to cytokines with anti-tumor activity. Mol Cancer. 2010 Jun 25;9:165. [2]. Novel STAT3 phosphorylation inhibitors exhibit potent growth-suppressive activity in pancreaticand breast cancer cells. Cancer Res. 2010 Mar 15;70(6):2445-54.

Solubility Data

Solubility (In Vitro)

DMSO: 92 mg/mL (198.0 mM) Water:<1 mg/mL Ethanol: 25 mg/mL warmed (53.8 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.38 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 (5.38 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 (5.38 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	2.1526 mL	10.7631 mL	21.5262 mL
	5 mM	0.4305 mL	2.1526 mL	4.3052 mL
	10 mM	0.2153 mL	1.0763 mL	2.1526 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.