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MedKoo Cat#: 522450 | Name: IT1t dihydrochloride
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

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.

Chemical Structure

IT1t dihydrochloride
IT1t dihydrochloride
CAS#1092776-63-0 (HCl salt)

Theoretical Analysis

MedKoo Cat#: 522450

Name: IT1t dihydrochloride

CAS#: 1092776-63-0 (HCl salt)

Chemical Formula: C21H36Cl2N4S2

Exact Mass: 478.1758

Molecular Weight: 479.57

Elemental Analysis: C, 52.60; H, 7.57; Cl, 14.78; N, 11.68; S, 13.37

Price and Availability

Size Price Availability Quantity
10mg USD 150.00 Ready to ship
25mg USD 250.00 Ready to ship
50mg USD 450.00 Ready to ship
100mg USD 750.00 Ready to ship
200mg USD 1,250.00 Ready to ship
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Related CAS #
1092776-63-0 (HCl salt) 864677-55-4 (free base)
Synonym
IT1t; IT1t dihydrochloride; Isothiourea-1t; IT1t HCl; IT1t hydrochloride;
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
More Info
Product Data
Product Data
Instruction
View handling instruction
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 mg/mL mM
Solubility
DMSO 17.4 36.28
Water 49.0 102.13
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 479.57 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.

Recalculate based on batch purity %
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.
1: Våbenø J, Haug BE, Rosenkilde MM. Progress toward rationally designed small-molecule peptide and peptidomimetic CXCR4 antagonists. Future Med Chem. 2015;7(10):1261-83. doi: 10.4155/fmc.15.64. PubMed PMID: 26144264. 2: Das D, Maeda K, Hayashi Y, Gavande N, Desai DV, Chang SB, Ghosh AK, Mitsuya H. Insights into the mechanism of inhibition of CXCR4: identification of Piperidinylethanamine analogs as anti-HIV-1 inhibitors. Antimicrob Agents Chemother. 2015 Apr;59(4):1895-904. doi: 10.1128/AAC.04654-14. Epub 2015 Jan 12. PubMed PMID: 25583709; PubMed Central PMCID: PMC4356787. 3: Cox BD, Prosser AR, Katzman BM, Alcaraz AA, Liotta DC, Wilson LJ, Snyder JP. Anti-HIV small-molecule binding in the peptide subpocket of the CXCR4:CVX15 crystal structure. Chembiochem. 2014 Jul 21;15(11):1614-20. doi: 10.1002/cbic.201402056. Epub 2014 Jul 2. PubMed PMID: 24990206. 4: Zhang C, Du C, Feng Z, Zhu J, Li Y. Hologram quantitative structure activity relationship, docking, and molecular dynamics studies of inhibitors for CXCR4. Chem Biol Drug Des. 2015 Feb;85(2):119-36. doi: 10.1111/cbdd.12377. Epub 2014 Jul 10. PubMed PMID: 24923360. 5: Yoshikawa Y, Oishi S, Kubo T, Tanahara N, Fujii N, Furuya T. Optimized method of G-protein-coupled receptor homology modeling: its application to the discovery of novel CXCR7 ligands. J Med Chem. 2013 Jun 13;56(11):4236-51. doi: 10.1021/jm400307y. Epub 2013 May 29. PubMed PMID: 23656360. 6: Bhattacharya S, Lam AR, Li H, Balaraman G, Niesen MJ, Vaidehi N. Critical analysis of the successes and failures of homology models of G protein-coupled receptors. Proteins. 2013 May;81(5):729-39. doi: 10.1002/prot.24195. Epub 2013 Feb 14. PubMed PMID: 23042299; PubMed Central PMCID: PMC3785289. 7: Rodríguez D, Gutiérrez-de-Terán H. Characterization of the homodimerization interface and functional hotspots of the CXCR4 chemokine receptor. Proteins. 2012 Aug;80(8):1919-28. doi: 10.1002/prot.24099. Epub 2012 May 25. PubMed PMID: 22513895. 8: Wu B, Chien EY, Mol CD, Fenalti G, Liu W, Katritch V, Abagyan R, Brooun A, Wells P, Bi FC, Hamel DJ, Kuhn P, Handel TM, Cherezov V, Stevens RC. Structures of the CXCR4 chemokine GPCR with small-molecule and cyclic peptide antagonists. Science. 2010 Nov 19;330(6007):1066-71. doi: 10.1126/science.1194396. Epub 2010 Oct 7. PubMed PMID: 20929726; PubMed Central PMCID: PMC3074590.

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JSF-2019

JSF-2019