WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H406111
CAS#: 1226895-15-3
Description: FLLL32, a novel curcumin analogue, is a potent STAT3 inhibitor. FLLL32 specifically reduced STAT3 phosphorylation at Tyr705 (pSTAT3) and induced apoptosis at micromolar amounts in human melanoma cell lines and primary melanoma cultures. FLLL32 promoted loss of cell proliferation at lower concentrations than curcumin leading to caspase-3- dependent apoptosis. FLLL32 may have potential for targeting multiple myeloma, glioblastoma, liver cancer, and colorectal cancer cells expressing constitutive STAT3 signaling.
Hodoodo Cat#: H406111
Name: FLLL32
CAS#: 1226895-15-3
Chemical Formula: C28H32O6
Exact Mass: 464.22
Molecular Weight: 464.550
Elemental Analysis: C, 72.39; H, 6.94; O, 20.66
Synonym: FLLL32; FLLL-32; FLLL 32
IUPAC/Chemical Name: (2E,2'E)-1,1'-(cyclohexane-1,1-diyl)bis(3-(3,4-dimethoxyphenyl)prop-2-en-1-one)
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+
SMILES Code: O=C(C1(C(/C=C/C2=CC=C(OC)C(OC)=C2)=O)CCCCC1)/C=C/C3=CC=C(OC)C(OC)=C3
Appearance: yellow solid powder
Purity: >97% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info:
| Biological target: | FLLL32, a synthetic analog of curcumina, is a JAK2/STAT3 dual inhibitor with anti-tumor activity. |
| In vitro activity: | FLLL32 was found to be a potent inhibitor of STAT3 phosphorylation, STAT3 DNA binding activity, and the expression of STAT3 downstream target genes in vitro, leading to the inhibition of cell proliferation as well as the induction of Caspase-3 and PARP cleavages in human multiple myeloma, glioblastoma, liver cancer, and colorectal cancer cell lines. However, FLLL32 exhibited little inhibition on some tyrosine kinases containing SH2 or both SH2 and SH3 domains, and other protein and lipid kinases using a kinase profile assay. FLLL32 was also more potent than four previously reported JAK2 and STAT3 inhibitors as well as curcumin to inhibit cell viability in these cancer cells. Furthermore, FLLL32 selectively inhibited the induction of STAT3 phosphorylation by Interleukin-6 but not STAT1 phosphorylation by IFN-γ. Reference: Mol Cancer. 2010 Aug 16;9:217. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20712901/ |
| In vivo activity: | The administration of FLLL32 resulted in significantly reduced tumor burdens in the MDA-MB-231 xenografted mice relative to their DMSO-treated counterparts (Figure 6A). Western blots performed with tumor tissue samples harvested from these mice also showed decreases in total levels of STAT3 phosphorylation. It was next examined whether FLLL32 would affect tumor growth and vascularity in a chicken embryo chorioallantoic membrane (CAM) human tumor xenograft model (Figure 6B–6D). It was found that gemcitabine, the standard chemotherapeutic agent for treatment of pancreatic cancer, reduced both tumor volume (Figure 6C) and tumor vascularity (Figure 6D) as compared to untreated embryos, but these decreases were statistically insignificant. FLLL32 administration resulted in a significant reduction in both tumor volume (Figure 6C) and tumor vascularity (Figure 6D) in the CAM xenograft assay. Reference: Cancer Res. 2010 Mar 15;70(6):2445-54. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20215512/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 92.0 | 198.04 | |
| Ethanol | 25.0 | 53.82 |
The following data is based on the product molecular weight 464.55 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | |
| In vitro protocol: | 1. Lin L, Deangelis S, Foust E, Fuchs J, Li C, Li PK, Schwartz EB, Lesinski GB, Benson D, Lü J, Hoyt D, Lin J. A novel small molecule inhibits STAT3 phosphorylation and DNA binding activity and exhibits potent growth suppressive activity in human cancer cells. Mol Cancer. 2010 Aug 16;9:217. doi: 10.1186/1476-4598-9-217. PMID: 20712901; PMCID: PMC2936338. 2. Lin L, Hutzen B, Zuo M, Ball S, Deangelis S, Foust E, Pandit B, Ihnat MA, Shenoy SS, Kulp S, Li PK, Li C, Fuchs J, Lin J. Novel STAT3 phosphorylation inhibitors exhibit potent growth-suppressive activity in pancreatic and breast cancer cells. Cancer Res. 2010 Mar 15;70(6):2445-54. doi: 10.1158/0008-5472.CAN-09-2468. Epub 2010 Mar 9. PMID: 20215512; PMCID: PMC2843552. |
| In vivo protocol: | 1. Lin L, Hutzen B, Zuo M, Ball S, Deangelis S, Foust E, Pandit B, Ihnat MA, Shenoy SS, Kulp S, Li PK, Li C, Fuchs J, Lin J. Novel STAT3 phosphorylation inhibitors exhibit potent growth-suppressive activity in pancreatic and breast cancer cells. Cancer Res. 2010 Mar 15;70(6):2445-54. doi: 10.1158/0008-5472.CAN-09-2468. Epub 2010 Mar 9. PMID: 20215512; PMCID: PMC2843552. 2. Onimoe GI, Liu A, Lin L, Wei CC, Schwartz EB, Bhasin D, Li C, Fuchs JR, Li PK, Houghton P, Termuhlen A, Gross T, Lin J. Small molecules, LLL12 and FLLL32, inhibit STAT3 and exhibit potent growth suppressive activity in osteosarcoma cells and tumor growth in mice. Invest New Drugs. 2012 Jun;30(3):916-26. doi: 10.1007/s10637-011-9645-1. Epub 2011 Feb 22. PMID: 21340507. |
1: Wu J, Patmore DM, Jousma E, Eaves DW, Breving K, Patel AV, Schwartz EB, Fuchs JR, Cripe TP, Stemmer-Rachamimov AO, Ratner N. EGFR-STAT3 signaling promotes formation of malignant peripheral nerve sheath tumors. Oncogene. 2013 Jan 14. doi: 10.1038/onc.2012.579. [Epub ahead of print] PubMed PMID: 23318430.
