IT1t

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种高效、选择性、口服生物可利用的 CXCR4 抑制剂，对 hCXCR4 的结合 IC50 为 8 nM，在 Ca2+ 动员测定中 IC50 为 1.1 nM。

A highly potent, selective, orally bioavailable CXCR4 inhibitor with binding IC50 of 8 nM for hCXCR4, IC50 of 1.1 nM in Ca2+-mobilization assays; inhibits HIV-1IIIB attachment with IC50 of 7 nM, and IC90 of 100 nM; also show promising anti-tumor effects, impairs the formation of TNBC early metastases in a zebrafish xenograft model.

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 ? 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.

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 .

Isothiourea 1t

GPCR/G Protein

Chemokine Receptor

Chemokine Receptor

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——

864677-55-4

406.65146

C21H34N4S2

>98% (HPLC)

DMSO

CC1(CN2C(=CSC2=N1)CSC(=NC3CCCCC3)NC4CCCCC4)C

Carbamimidothioic acid, N,N'-dicyclohexyl-, (5,6-dihydro-6,6-dimethylimidazo[2,1-b]thiazol-3-yl)methyl ester

(-20℃)

With Ice Pack

≥ 2 years