- Three [...] -99m or rhenium -188 labeling ring RGD derivatives, its preparation method and comprising the said derivative as an active ingredient used for the diagnosis or treatment of diseases related to angiogenesis pharmaceutical composition
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The present invention relates to a tricarbonyl technetium-99m or rhenium-188 label ring RGD derivative, a preparation method thereof, and a pharmaceutical composition containing the derivative as an active ingredient for use in the diagnosis or treatment of angiogenesis-related diseases. The tricarbonyl technetium-99m or rhenium-188 label ring RGD derivative of the present invention has a high subnanomolar affinity to avss3 integrin (also called as a vitronectin receptor that is activated in an angiogenic action induced by a tumor, reflects a high tumor image after an animal in which cancer cells are transplanted received an initial intake of the tricarbonyl technetium-99m label ring RGD derivative, and acts exclusively upon cancer cells having selectively activated avss3 integrin because of a substantially low intake into the liver and intestines,; compared to existing known radioactive isotope label ring RGD derivatives. These results show that the rhenium-188 label derivative, a therapeutic nuclide using the same precursor as used in the technetium-99m label, effectively inhibits the growth of a tumor and demonstrates therapeutic efficacy when administered via tail vein injection to an animal model of a tumor, compared to a case where only saline has been injected, thereby making it useful as a medicine for the diagnosis or treatment of angiogenesis-related diseases.
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Paragraph 0171-0172
(2016/11/17)
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- Design of a binuclear Ni(II)-iminodiacetic acid (IDA) complex for selective recognition and covalent labeling of His-tag fused proteins
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Selective protein labeling with a small molecular probe is a versatile method for elucidating protein functions under live-cell conditions. In this Letter, we report the design of the binuclear Ni(II)-iminodiacetic acid (IDA) complex for selective recognition and covalent labeling of His-tag-fused proteins. We found that the Ni(II)-IDA complex 1-2Ni(II) binds to the His6-tag (HHHHHH) with a strong binding affinity (Kd = 24 nM), the value of which is 16-fold higher than the conventional Ni(II)-NTA complex (Kd = 390 nM). The strong binding affinity of the Ni(II)-IDA complex was successfully used in the covalent labeling and fluorescence bioimaging of a His-tag fused GPCR (G-protein coupled receptor) located on the surface of living cells.
- Takahira, Ikuko,Fuchida, Hirokazu,Tabata, Shigekazu,Shindo, Naoya,Uchinomiya, Shohei,Hamachi, Itaru,Ojida, Akio
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p. 2855 - 2858
(2014/06/10)
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- Synthesis and biological evaluation of RGD peptides with the 99mTc/188Re chelated iminodiacetate core: Highly enhanced uptake and excretion kinetics of theranostics against tumor angiogenesis
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To develop a companion set of RGD-based agents for diagnostic and radiotherapeutic purposes, facile incorporation of 99mTc(CO) 3 or 188Re(CO)3 into the same precursor produced, respectively, a structurally and functionally matched radiodiagnostic and radiotherapeutic - or theranostic - pair. This work presents the synthesis of two 99mTc-labeled RGD monomers (4 and 5) along with a 99mTc-labeled RGD dimer (6) and an investigation of the influence of the small-sized and negatively charged 99mTc-iminodiacetate (IDA) core on the in vitro and in vivo behavior of these three different RGD analogs for imaging integrin αvβ3 expression. Among the three 99mTc-IDA-RGD analogs, 6 exhibited the highest integrin binding affinity with an IC50 value of 0.5 nM and a tumor uptake with an ID/g value of 12.3 ± 5.15% at 60 min post-injection, whereas liver and intestinal levels remained relatively low with good metabolic stability (>97%), presumably because of the overall negative charge of the radiometal chelating system. Both 99mTc/188Re-labeled compounds (6 and 7), which were prepared from the precursor (18), provided a good tumor accumulation and a clearly visible image of the tumor with high contrast, as compared to the contralateral background in the U87-MG xenograft model. These data support the use of 99mTc- and 188Re-IDA-D-[c(RGDfK)] 2 as a matched radio-theragnostic pair that can be used to individualize radiotherapy for angiogenesis-dependent cancer.
- Lee, Byung Chul,Moon, Byung Seok,Kim, Ji Sun,Jung, Jae Ho,Park, Hyun Soo,Katzenellenbogen, John A.,Kim, Sang Eun
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p. 782 - 792
(2013/04/10)
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- Peptides for Treatment of Obesity
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The present invention relates to novel peptide compounds which are effective in modulating one or more melanocortin receptor types, to the use of the compounds in therapy, to methods of treatment comprising administration of the compounds to patients in need thereof, and to the use of the compounds in the manufacture of medicaments. The compounds of the invention are of particular interest in relation to the treatment of obesity as well as a variety of diseases or conditions associated with obesity.
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Page/Page column
(2013/03/26)
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- A luminescent sensor for tyrosine phosphorylation
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We have developed a luminogenic probe for tyrosine phosphorylation based on a short peptide sequence containing an iminodiacetate moiety near the site of phosphorylation. In response to kinase activity, the probe provides a strong luminescence enhancement, resulting from the increased ability of the probe to bind and sensitize Tb3+ and Eu3+ ions upon phosphorylation.
- Tremblay, Matthew S.,Lee, Minhee,Sames, Dalibor
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- Stereocontrolled Synthesis of DTPA Analogues Branched in the Ethylene Unit
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Stereochemically controlled synthesis of diethylenetriaminepentaacetic acid (DTPA) analogues substitued on the ethylene backbones with methyl groups, the chiral center α to the terminal nitrogen being derived from (S)- or (R)-alanine, has been achieved.The key intermediate (S)-propylenediaminetriacetic acid triester was synthesized via selective detosylation of the alkylation product derived from (S)-alanine and tert-butyl glycinate.Attaching the remaining modified alanine (or glycine) fragment through acyl coupling and then selective reduction of the amide followed by hydrolysis of the esters afforded the substitued DTPA analogues.Ester differentiation has been accomplished through alkylation rather than acylation of the (S)-propylenediaminetriacetic acid triester.A byproduct from this alkylation is the oxazoloisoindole formed by internal alkylation of the oxygen of the phthaloyl protecting group.Phthaloyl deprotection followed by dialkylation afforded the ester-differentiated (S,S)-dipropylenetriaminepentaacetic esters.The enantiomeric purity of the chiral intermediates (S)-alaninol and (S)-propylenediamines were determined by HPLC using epimeric standards.
- Grote, Christopher W.,Kim, Dong Jin,Rapoport, Henry
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p. 6987 - 6997
(2007/10/03)
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