L48H37 (L 48H37; L-48H37; L48H-37), a Curcumin analog with improved chemical stability, is a novel and potent myeloid differentiation 2 (MD2) inhibitor with the potential to be used for the treatment of of sepsis or lung injury. L48H37 inhibits the interaction and signaling transduction of LPS-TLR4/MD2.
Physicochemical Properties
| Molecular Formula | C27H33NO7 |
| Molecular Weight | 483.56 |
| Exact Mass | 483.226 |
| CAS # | 343307-76-6 |
| PubChem CID | 6523614 |
| Appearance | Light yellow to yellow solid powder |
| LogP | 4.047 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 8 |
| Rotatable Bond Count | 9 |
| Heavy Atom Count | 35 |
| Complexity | 668 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | CCN1C/C(=C\C2=CC(=C(C(=C2)OC)OC)OC)/C(=O)/C(=C/C3=CC(=C(C(=C3)OC)OC)OC)/C1 |
| InChi Key | IOFNKUXFKVPLPF-LQGKIZFRSA-N |
| InChi Code | InChI=1S/C27H33NO7/c1-8-28-15-19(9-17-11-21(30-2)26(34-6)22(12-17)31-3)25(29)20(16-28)10-18-13-23(32-4)27(35-7)24(14-18)33-5/h9-14H,8,15-16H2,1-7H3/b19-9+,20-10+ |
| Chemical Name | (3E,5E)-1-ethyl-3,5-bis[(3,4,5-trimethoxyphenyl)methylidene]piperidin-4-one |
| Synonyms | L48H37 L48 H37 L48-H37L 48H37L-48H 37L48H-37 |
| 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 | L48H37 suppresses inflammation brought on by LPS, particularly the synthesis and expression of TNF-α and IL-6 in mouse macrophages [1]. L48H37 is more effective than curcumin in lung cancer cells, reducing the viability of A549 and H460 cells with IC50 values of 2.3 µM and 5.3 µM, respectively, over a 24-hour period (0-20 µM). With an IC50 of 21 μM, it exhibits minimal cytotoxicity against normal human lung epithelial cells (BEAS-2B) [2]. L48H37 (1, 2, or 4 µM; 16 hours) enhances the expression of p53 while dose-dependently inhibiting the expression of Cdc2 and p-Cdc2. In H460 and A549 cells, it also revealed lower levels of the anti-apoptotic protein Bcl-2 and higher amounts of cleaved poly(ADP-ribosyl) polymerase (PARP) [2]. Increased DCF levels in H460 and A549 cells indicate that L48H37 (4 µM; 16 hours) rapidly and dose-dependently increases intracellular ROS levels [2]. |
| ln Vivo | L48H37 (ip; 5 mg or 10 mg/kg; once daily; 11 days) has anticancer action in mice and reduces the formation of H460 xenograft tumors [1]. |
| Cell Assay |
Cell Viability Assay[2] Cell Types: A549 and H460 cells; BEAS-2B Cell Tested Concentrations: 0.625, 1.25, 2.5, 5, 7.5, 10 and 20 µM Incubation Duration: 24 hrs (hours) Experimental Results: Inhibition of lung cancer cell growth in a concentration-dependent manner . Western Blot Analysis[2] Cell Types: A549 and H460 Cell Tested Concentrations: 0.625, 1.25, 2.5, 5, 7.5, 10 and 20 µM Incubation Duration: 24 hrs (hours) Experimental Results: diminished expression of p-Cdc2, Cdc2 and Bcl-2 in 2 lung cancers cell. |
| Animal Protocol |
Animal/Disease Models: 5weeks old athymic BALB/cA nu/nu female mice (18-22 g) [2] Doses: 5 mg or 10 mg/kg Route of Administration: intraperitoneal (ip) injection; one time/day; 11-day Experimental Results: vs. Tumor wet weight was diminished compared to vehicle control. The levels of p-STAT3 in vivo were diminished, and the levels of p-EIF2α and ATF4 were increased. No obvious structural changes were shown in mice. |
| References |
[1]. Curcumin Analog L48H37 Prevents Lipopolysaccharide-Induced TLR4 Signaling Pathway Activation and Sepsis via Targeting MD2. J Pharmacol Exp Ther. 2015 Jun;353(3):539-50. [2]. Curcumin analog L48H37 induces apoptosis through ROS-mediated endoplasmic reticulum stress and STAT3 pathways in human lung cancer cells. Mol Carcinog. 2017 Jul;56(7):1765-1777. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~50 mg/mL (~103.40 mM) |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0680 mL | 10.3400 mL | 20.6800 mL | |
| 5 mM | 0.4136 mL | 2.0680 mL | 4.1360 mL | |
| 10 mM | 0.2068 mL | 1.0340 mL | 2.0680 mL |