IT1t dihydrochloride

Category	Human immunodeficiency Virus (HIV)
CAS	1092776-63-0
Description	IT1t dihydrochloride is a potent and orally CXCR4 antagonist (IC50 = 1.1 nM in calcium mobilization assays).

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Product Information

Synonyms	N,N'-Dicyclohexylcarbamimidothioic acid (5,6-dihydro-6,6-dimethylimidazo[2,1-b]thiazol-3-yl)methyl ester dihydrochloride; IT1t; IT1t dihydrochloride
IUPAC Name	(6,6-dimethyl-5H-imidazo[2,1-b][1,3]thiazol-3-yl)methyl N,N'-dicyclohexylcarbamimidothioate;dihydrochloride
Molecular Weight	479.57
Molecular Formula	C21H34N4S2.2HCl
Canonical SMILES	CC1(C)N=C2SC=C(CS/C(NC3CCCCC3)=N\C4CCCCC4)N2C1.[H]Cl.[H]Cl
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)
InChIKey	HFXJOXOIINQOEB-UHFFFAOYSA-N
Purity	≥98% (HPLC)
Solubility	Soluble to 100 mM in DMSO and to 100 mM in ethanol
Appearance	Off-White Solid
Storage	Store at +4°C
Complexity	614
Exact Mass	478.1758449
In Vitro	The CXCR4 is involved in chemotaxis and serves as a coreceptor for T-tropic HIV-1 viral entry and in cancer metastasis. IT1t is a small, drug-like, isothiourea derivative. IT1t shows very potent and dose-dependent inhibition of the CXCL12/CXCR4 interaction with an IC50 of 2.1 nM. This calcium flux is also inhibited by IT1t with an IC50 of 23.1. Strong electron density is observed for IT1t in the binding cavity of both subunits of the CXCR4 homodimer. In dimers of CXCR4 bound to IT1t, the monomers interact only at the extracellular side of helices V and VI, leaving at least a 4 Å gap between the intracellular regions, which is presumably filled by lipids. The IT1t compound and CVX15 peptide have both been characterized as competitive inhibitors of CXCL12, and many of the receptor-ligand contacts in the co-crystal structures presented are important for CXCL12 binding, including the acidic Asp187, Glu2887.39 and Asp972.63. The binding site of IT1t may point to the major anchor region for this domain.
In Vivo	IT1t reduces the formation of TNBC early metastases in the zebrafish xenograft model. Tumor cell invasion at the metastatic site is effectively reduced upon CXCR4 silencing (Fig. 7B), similar to the antagonist IT1t .
Target	CXCL12/CXCR4:2.1 nM (IC50) HIV-1 (X4):14.2 nM (IC50, in MT-4 cells) HIV-1 (X4):19 nM (IC50, in PBMCs)