WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 522450
CAS#: 1092776-63-0 (HCl salt)
Description: IT1t is a potent and selective CXCR4 antagonist (IC50 = 1.1 nM in calcium mobilization assays). IT1t may be potential useful as anti-HIV agent. The CXC chemokine receptor 4 (CXCR4) is an alpha G-protein coupled chemokine receptor that is widely expressed on most hematopoietic cells, predominantly leukocytes including neutrophils, monocytes, and macrophages.
MedKoo Cat#: 522450
Name: IT1t dihydrochloride
CAS#: 1092776-63-0 (HCl salt)
Chemical Formula: C21H36Cl2N4S2
Exact Mass:
Molecular Weight: 479.567
Elemental Analysis: C, 52.60; H, 7.57; Cl, 14.78; N, 11.68; S, 13.37
Related CAS #: 1092776-63-0 (HCl salt) 864677-55-4 (free base)
Synonym: IT1t; IT1t dihydrochloride; Isothiourea-1t;
IUPAC/Chemical Name: (6,6-dimethyl-5,6-dihydroimidazo[2,1-b]thiazol-3-yl)methyl (Z)-N,N'-dicyclohexylcarbamimidothioate dihydrochloride
InChi Key: HFXJOXOIINQOEB-UHFFFAOYSA-N
InChi Code: InChI=1S/C21H34N4S2.2ClH/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);2*1H
SMILES Code: CC1(C)N=C2SC=C(CS/C(NC3CCCCC3)=N\C4CCCCC4)N2C1.[H]Cl.[H]Cl
Appearance: Solid powder
Purity: >95% (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
| Biological target: | IT1t dihydrochloride is a potent CXCR4 antagonist; inhibits CXCL12/CXCR4 interaction with an IC50 of 2.1 nM. |
| In vitro activity: | Additionally, binding of the CXCR4 antagonist IT1t-a small drug-like isothiourea derivative-rapidly destabilizes the oligomeric structure, whereas AMD3100, another well-characterized CXCR4 antagonist, does not. Although a mutation that regulates constitutive activity of CXCR4 also results in monomerization of the receptor, binding of IT1t to this variant promotes receptor dimerization. Reference: J Biol Chem. 2021 Jan-Jun;296:100139. https://pubmed.ncbi.nlm.nih.gov/33268380/ |
| In vivo activity: | Tumor cell invasion at the metastatic site was effectively reduced upon CXCR4 silencing (Fig. 7B), similar to the antagonist IT1t (Fig. 7C). Therefore, using chemical and genetic approaches, this study demonstrates that CXCR4 signaling inhibition reduces the formation of TNBC early metastases in zebrafish xenograft models and describe IT1t as a potential therapeutic for metastatic TNBC. Reference: Dis Model Mech. 2016 Feb;9(2):141-53. https://pubmed.ncbi.nlm.nih.gov/26744352/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 17.4 | 36.28 | |
| Water | 48.98 | 102.13 |
The following data is based on the product molecular weight 479.567 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: | 1. Ward RJ, Pediani JD, Marsango S, Jolly R, Stoneman MR, Biener G, Handel TM, Raicu V, Milligan G. Chemokine receptor CXCR4 oligomerization is disrupted selectively by the antagonist ligand IT1t. J Biol Chem. 2021 Jan-Jun;296:100139. doi: 10.1074/jbc.RA120.016612. Epub 2020 Dec 6. PMID: 33268380; PMCID: PMC7949023. 2. Smith N, Rodero MP, Bekaddour N, Bondet V, Ruiz-Blanco YB, Harms M, Mayer B, Bader-Meunier B, Quartier P, Bodemer C, Baudouin V, Dieudonné Y, Kirchhoff F, Sanchez Garcia E, Charbit B, Leboulanger N, Jahrsdörfer B, Richard Y, Korganow AS, Münch J, Nisole S, Duffy D, Herbeuval JP. Control of TLR7-mediated type I IFN signaling in pDCs through CXCR4 engagement-A new target for lupus treatment. Sci Adv. 2019 Jul 10;5(7):eaav9019. doi: 10.1126/sciadv.aav9019. PMID: 31309143; PMCID: PMC6620093. 3. Tulotta C, Stefanescu C, Beletkaia E, Bussmann J, Tarbashevich K, Schmidt T, Snaar-Jagalska BE. Inhibition of signaling between human CXCR4 and zebrafish ligands by the small molecule IT1t impairs the formation of triple-negative breast cancer early metastases in a zebrafish xenograft model. Dis Model Mech. 2016 Feb;9(2):141-53. doi: 10.1242/dmm.023275. Epub 2016 Jan 7. PMID: 26744352; PMCID: PMC4770151. |
| In vitro protocol: | 1. Ward RJ, Pediani JD, Marsango S, Jolly R, Stoneman MR, Biener G, Handel TM, Raicu V, Milligan G. Chemokine receptor CXCR4 oligomerization is disrupted selectively by the antagonist ligand IT1t. J Biol Chem. 2021 Jan-Jun;296:100139. doi: 10.1074/jbc.RA120.016612. Epub 2020 Dec 6. PMID: 33268380; PMCID: PMC7949023. 2. Smith N, Rodero MP, Bekaddour N, Bondet V, Ruiz-Blanco YB, Harms M, Mayer B, Bader-Meunier B, Quartier P, Bodemer C, Baudouin V, Dieudonné Y, Kirchhoff F, Sanchez Garcia E, Charbit B, Leboulanger N, Jahrsdörfer B, Richard Y, Korganow AS, Münch J, Nisole S, Duffy D, Herbeuval JP. Control of TLR7-mediated type I IFN signaling in pDCs through CXCR4 engagement-A new target for lupus treatment. Sci Adv. 2019 Jul 10;5(7):eaav9019. doi: 10.1126/sciadv.aav9019. PMID: 31309143; PMCID: PMC6620093. |
| In vivo protocol: | 1. Tulotta C, Stefanescu C, Beletkaia E, Bussmann J, Tarbashevich K, Schmidt T, Snaar-Jagalska BE. Inhibition of signaling between human CXCR4 and zebrafish ligands by the small molecule IT1t impairs the formation of triple-negative breast cancer early metastases in a zebrafish xenograft model. Dis Model Mech. 2016 Feb;9(2):141-53. doi: 10.1242/dmm.023275. Epub 2016 Jan 7. PMID: 26744352; PMCID: PMC4770151. |
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