IT-901 (IT901) is a novel, oral and potent c-Rel Inhibitor targeting the NF-κB subunit of c-Rel with anticancer effects. It has the potential for treating human lymphoid tumors and ameliorate graft-versus-host disease (GVHD).
Physicochemical Properties
| Molecular Formula | C17H14N2O4S |
| Molecular Weight | 342.369062900543 |
| Exact Mass | 342.067 |
| CAS # | 1584121-99-2 |
| PubChem CID | 90082813 |
| Appearance | Orange to red solid powder |
| LogP | 2.8 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 3 |
| Heavy Atom Count | 24 |
| Complexity | 555 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | S=C1NC(/C(/C(N1)=O)=C\C1=C(C=C(C2C=CC=CC1=2)OC)OC)=O |
| InChi Key | JHOPCCOYRKEHQU-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C17H14N2O4S/c1-22-13-8-14(23-2)11(9-5-3-4-6-10(9)13)7-12-15(20)18-17(24)19-16(12)21/h3-8H,1-2H3,(H2,18,19,20,21,24) |
| Chemical Name | 5-[(2,4-dimethoxynaphthalen-1-yl)methylidene]-2-sulfanylidene-1,3-diazinane-4,6-dione |
| Synonyms | IT901 IT 901 IT-901 |
| 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 | In viable ABC and GCB DLBCL cells, IT-901 (1, 3, 5 μM) reduces cell growth throughout a 24-hour period[1]. IT-901 (3 μM) reduces cell viability in a dose-dependent manner; in all studied cell lines, with the exception of HBL1, at least 60% of cells remained viable 48 hours following IT-901 treatment (4 μM)[1]. Documents IT-901 (1, 5, 10 μM; for 6 hours) Reduced expression of the inhibitory component IκBα in both its phosphorylated and non-phosphorylated forms in primary CLL cells and cell lines, as well as decreased expression of p65 and p50 in nuclear and cytosolic fractions[2]. IT-901/GDM-12 effectively blocks IL-2 secretion at 5 μM, but its IC50 for c-Rel is 2.9 μM[1]. IT-901 concentrations more than 10 μM are progressively harmful and have the potential to cause healthy cells to undergo apoptosis[1]. With IC50 values ranging from 3μM to 4μM, IT-901 suppresses the development of both activated B-like (ABC) and germinal center B-like (GCB) cell lines[1]. |
| ln Vivo | Acute GVHD can be effectively treated with IT-901 (24 mg/kg; IP; every other day for two weeks) without compromising anti-tumor activity[1]. IT-901 (12–20 mg/kg; IP) raises T1/2 and Cmax, which enhances the PK profile[1]. |
| Cell Assay |
Cell Proliferation Assay[1] Cell Types: TMD8 and SU-DHL8 cells Tested Concentrations: 1, 3, 5 μM Incubation Duration: For 24 hrs (hours) Experimental Results: Resulted in diminished proliferation of viable ABC and GCB DLBCL cells. Cell Viability Assay[1] Cell Types: SU-DHL8 and TMD8 cells Tested Concentrations: 3 μM Incubation Duration: For 24 hrs (hours) Experimental Results: diminished cell viability in a dose-dependent fashion. Western Blot Analysis[2] Cell Types: Primary chronic lymphocytic leukemia (CLL) cells and cell lines Tested Concentrations: 1, 5, 10 μM Incubation Duration: For 6 hrs (hours) Experimental Results: Documented Diminished expression of p65 and p50 in nuclear and cytosolic fractions and also diminished the expression of the inhibitory subunit IκBα both in the phosphorylated and non-phosphorylated forms. |
| Animal Protocol |
Animal/Disease Models: BALB/C-Tg (NFkB-RE-luc)-Xen mice with 6-9 weeks old[1] Doses: 24 mg/kg Route of Administration: IP; every other day for 2 weeks Experimental Results: Had an effective treatment of acute GVHD without impairing anti-tumor activity. |
| References |
[1]. Characterization of a c-Rel Inhibitor That Mediates Anticancer Properties in HematologicMalignancies by Blocking NF-κB-Controlled Oxidative Stress Responses. Cancer Res. 2016 Jan 15;76(2):377-89. [2]. Targeting metabolism and survival in chronic lymphocytic leukemia and Richter syndrome cellsby a novel NF-κB inhibitor. Haematologica. 2017 Nov;102(11):1878-1889. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~12.5 mg/mL (~36.51 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 | 2.9208 mL | 14.6041 mL | 29.2082 mL | |
| 5 mM | 0.5842 mL | 2.9208 mL | 5.8416 mL | |
| 10 mM | 0.2921 mL | 1.4604 mL | 2.9208 mL |