IT1t is a novel, potent and selective CXCR4 antagonist that inhibits CXCL12/CXCR4 interaction with an IC50 of 1.1 nM in calcium mobilization assay, it can be potentially used as an anti-HIV agent.
Physicochemical Properties
| Molecular Formula | C21H34N4S2 |
| Molecular Weight | 406.651462078094 |
| Exact Mass | 406.222 |
| CAS # | 864677-55-4 |
| Related CAS # | IT1t dihydrochloride;1092776-63-0 |
| PubChem CID | 25147749 |
| Appearance | Typically exists as solid at room temperature |
| Density | 1.3±0.1 g/cm3 |
| Boiling Point | 529.8±60.0 °C at 760 mmHg |
| Flash Point | 274.2±32.9 °C |
| Vapour Pressure | 0.0±1.4 mmHg at 25°C |
| Index of Refraction | 1.675 |
| LogP | 6.16 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 6 |
| Heavy Atom Count | 27 |
| Complexity | 614 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | C(=NC1CCCCC1)(SCC1=CSC2=NC(C)(C)CN21)NC1CCCCC1 |
| InChi Key | OOSUDWRRWZVFEB-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C21H34N4S2/c1-21(2)15-25-18(14-27-20(25)24-21)13-26-19(22-16-9-5-3-6-10-16)23-17-11-7-4-8-12-17/h14,16-17H,3-13,15H2,1-2H3,(H,22,23) |
| Chemical Name | (6,6-dimethyl-5H-imidazo[2,1-b][1,3]thiazol-3-yl)methyl N,N'-dicyclohexylcarbamimidothioate |
| 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 addition to being a coreceptor for T-tropic HIV-1 viral entry and cancer metastasis, CXCR4 is implicated in chemotaxis. IT1t is a tiny, drug-like derivative of isothiourea. With an IC50 of 2.1 nM, IT1t exhibits very strong dose-dependent suppression of the CXCL12/CXCR4 interaction. IT1t also inhibits this calcium flux, with an IC50 of 23.1[1]. In the binding cavity containing the two subunits of the CXCR4 homodimer, a significant electron density of IT1t is seen. The monomers of CXCR4 dimers linked to IT1t only engage with helices V and VI on their extracellular side, leaving at least 4 Å of space between intracellular regions that may be occupied by lipids. Competitive inhibitors of CXCL12, such as the IT1t molecule and the CVX15 peptide, have been identified. Numerous receptor-ligand interactions in the cocrystal structure, such as acidic Asp187, Glu2887.39, and Asp972.63, are crucial for CXCL12 binding. The primary anchoring area of this domain may be indicated by the binding site of IT1t [2]. |
| ln Vivo | IT1t inhibits the development of TNBC early metastases in zebrafish xenograft models. Similar to the antagonist IT1t, CXCR4 silencing will significantly decrease tumor cell invasion at the metastatic site (Figure 7B). |
| References |
[1]. Comparison of cell-based assays for the identification and evaluation of competitive CXCR4 inhibitors. PLoS One. 2017 Apr 14;12(4):e0176057. [2]. Structures of the CXCR4 chemokine GPCR with small-molecule and cyclic peptide antagonists. Science. 2010 Nov 19;330(6007):1066-71. [3]. Inhibition of signaling between human CXCR4 and zebrafish ligands by the small molecule IT1timpairs the formation of triple-negative breast cancer early metastases in a zebrafish xenograft model. Dis Model Mech. 2016 Feb;9(2):141-53. |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| 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 | 2.4591 mL | 12.2956 mL | 24.5912 mL | |
| 5 mM | 0.4918 mL | 2.4591 mL | 4.9182 mL | |
| 10 mM | 0.2459 mL | 1.2296 mL | 2.4591 mL |