AMD 3465 - CAS 185991-24-6
Catalog number: 185991-24-6
Category: Inhibitor
Please be kindly noted products are not for therapeutic use. We do not sell to patients.
Molecular Formula:
C24H38N6
Molecular Weight:
410.60
COA:
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Targets:
CXCR
Description:
AMD 3465,a N-pyridinylmethylene monocyclam, is a selective antagonist of CXCL12/CXCR4-mediated interactions including ligand binding and receptor activation. With its enhanced potency against the CXCR4 receptor compared with plerixafor, AMD 3465 has been
Appearance:
Light-pink solid
Synonyms:
N-(pyridin-2-ylmethyl)-1-[4-(1,4,8,11-tetrazacyclotetradec-1-ylmethyl)phenyl]methanamine;hexahydrobromideAMD 3465 hexahydrobromide185991-07-5185991-24-6AMD3465 6 HBrC24H38N6.6BrHAMD3465; AMD 3465; AMD-3465GENZ-644494 N-(1,4,8,11- tetraazacyclotetradecanyl-1,4-phenylen
Solubility:
Soluble to 93.2 mg/ml in water, and to 34.0 mg/ml in DMSO
Storage:
Store in a cool and dry place and at 0 - 4℃ for short term (days to weeks) or -73℃ for long term (months to years).
MSDS:
Inquire
Shelf Life:
2 years
Boiling Point:
571.3±50.0 °C | Condition: Press: 760 Torr
Melting Point:
200-205 °C (decomp)
Density:
1.022±0.06 g/cm3
InChIKey:
ARHBIBDGWDRBJH-UHFFFAOYSA-N
InChI:
1S/C24H38N6.6BrH/c1-2-13-29-24(5-1)20-28-19-22-6-8-23(9-7-22)21-30-17-4-12-26-15-14-25-10-3-11-27-16-18-30;;;;;;/h1-2,5-9,13,25-28H,3-4,10-12,14-21H2;6*1H
Canonical SMILES:
C1CNCCNCCCN(CCNC1)CC2=CC=C(C=C2)CNCC3=CC=CC=N3.Br.Br.Br.Br.Br.Br
1.AMD3465, a monomacrocyclic CXCR4 antagonist and potent HIV entry inhibitor.
Hatse S;Princen K;De Clercq E;Rosenkilde MM;Schwartz TW;Hernandez-Abad PE;Skerlj RT;Bridger GJ;Schols D Biochem Pharmacol. 2005 Sep 1;70(5):752-61.
The chemokine receptors CCR5 and CXCR4 function as coreceptors for human immunodeficiency virus (HIV) and are attractive targets for the development of anti-HIV drugs. The most potent CXCR4 antagonists described until today are the bicyclams. The prototype compound, AMD3100, exhibits potent and selective anti-HIV activity against CXCR4-using (X4) viruses and showed antiviral efficacy in X4 HIV-1-infected persons in a phase II clinical trial. However, AMD3100 lacks oral bioavailability due to its high overall positive charge. Initial structure-activity relationship studies with bicyclam analogues suggested that the bis-macrocyclic structure was a prerequisite for anti-HIV activity. Now, we report that the N-pyridinylmethylene cyclam AMD3465, which lacks the structural constraints mentioned above, fully conserves all the biological properties of AMD3100. Like AMD3100, AMD3465 blocked the cell surface binding of both CXCL12 (the natural CXCR4 ligand), and the specific anti-CXCR4 monoclonal antibody 12G5. AMD3465 dose-dependently inhibited intracellular calcium signaling, chemotaxis, CXCR4 endocytosis and mitogen-activated protein kinase phosphorylation induced by CXCL12. Compared to the bicyclam AMD3100, AMD3465 was even 10-fold more effective as a CXCR4 antagonist, while showing no interaction whatsoever with CCR5.
2.New advances in HIV entry inhibitors development.
Rusconi S;Scozzafava A;Mastrolorenzo A;Supuran CT Curr Drug Targets Infect Disord. 2004 Dec;4(4):339-55.
Considerable advances have been made in the last years in the design of derivatives acting as inhibitors of HIV entry and fusion. The discovery of chemokines focused the attention on cellular coreceptors used by the virus for entering within cells, and consequently the various steps of such processes have been characterized in detail. Intense research led to a wide range of effective compounds that are able to inhibit the initial steps of HIV life cycle. All steps in the process of HIV entry into the cell may be targeted by specific compounds that may be developed as novel types of antiretrovirals. Thus, several inhibitors of the gp120-CD4 interaction have been detected so far (zintevir, FP-21399 and BMS-378806 in clinical trials). Small molecule chemokine receptor antagonists acting as HIV entry inhibitors also were described in the last period, which interact both with the CXCR4 coreceptor (such as AMD3100; AMD3465; ALX40-4C; T22, T134 and T140), or which are antagonist of the CCR5 coreceptor (TAK-779, TAK-220, SCH-C, SCH-D, E913, AK-602, UK-427857 and NSC 651016 in clinical trials), together with new types of fusion inhibitors possessing the same mechanism of action as enfuvirtide (such as T1249).
3.Bridged cyclams as imaging agents for chemokine receptor 4 (CXCR4).
Woodard LE;De Silva RA;Behnam Azad B;Lisok A;Pullambhatla M;G Lesniak W;Mease RC;Pomper MG;Nimmagadda S Nucl Med Biol. 2014 Aug;41(7):552-61. doi: 10.1016/j.nucmedbio.2014.04.081. Epub 2014 Apr 21.
Over-expression of chemokine receptor 4 (CXCR4) is present in a majority of cancers, has been linked to an aggressive phenotype, and may indicate the metastatic potential of primary tumor. Several CXCR4 targeted therapeutics are in clinical trials and the development of the corresponding imaging agents is an area of active interest. Previously, (64)Cu-labeled imaging agents for CXCR4 have provided clear images of CXCR4-bearing tissues in relevant experimental models but demonstrated fast washout from tissues harboring receptor. Addition of stabilizing bridges is known to provide more robust chelator-Cu(II) complexes. In addition, bridged cyclam-based CXCR4 binding agents demonstrated increased receptor residence times relative to existing agents. Based on that knowledge we synthesized several bridged cyclam analogs of AMD3465, a monocyclam-based CXCR4 imaging agent, to increase the retention time of the tracer bound to the receptor to allow for protracted imaging and improved target-to-non-target ratios. Specific accumulation of two radiolabeled, cross-bridged analogs ([(64)Cu] RAD1-24 and [(64)Cu]RAD1-52) was observed in U87-stb-CXCR4 tumors in both PET/CT imaging and biodistribution studies.
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