Edotreotide

Edotreotideyog radioactive-labeled diagnostic and therapeutic drug, belongs rau chav kawm ntawm somatostatin analogues. Nws cov txheej txheem tseem ceeb yog txhawm rau xaiv lub hom phiaj ntawm lub hlwb nrog ntau tshaj somatostatin receptors, tshwj xeeb tshaj yog cov hom SSTR2 subtype pom nyob rau saum npoo ntawm neuroendocrine qog hlwb. Thaum nws ua ke nrog positron radionuclides xws li gallium-68 (⁶⁸Ga), nws dhau los ua cov cuab yeej kuaj mob zoo tshaj plaws (xws li ⁶⁸Ga-Edotreotide), uas tuaj yeem txheeb xyuas qhov tseeb, theem thiab ntsuas qhov ua tau zoo ntawm cov qog nqaij hlav los ntawm cov duab tomography / positron. Thaum nws ua ke nrog kev kho mob beta-duab tshav radionuclides xws li lutetium-177 (¹⁷⁷Lu) lossis yttrium-90 (⁹⁰Y), nws hloov mus rau hauv cov tshuaj siv tshuaj radioligand, uas tuaj yeem xa cov xov tooj cua ncaj qha mus rau sab hauv ntawm cov qog nqaij hlav puas tsuaj, siv hluav taws xob hauv kev kho mob los ntawm kev siv hluav taws xob. metastatic neuroendocrine qog. Yog li ntawd, Edotreotide embodies lub tswvyim siab tshaj ntawm "kev kuaj mob thiab kev kho mob kev koom ua ke", muab ib tug tseem ceeb txhais tau tias rau tag nrho cov chav kawm ntawm kev tswj ntawm neuroendocrine hlav.

 

Peb cov khoom tsim

 

Edotreotide COA

Edotreotideyog ib qho kev sib xyaw ua ke ntawm cyclic octapeptide compound, uas yog tsev neeg ntawm somatostatin analogues. Nws muaj cov tshuaj lom neeg tshwj xeeb thiab ua lub luag haujlwm tseem ceeb hauv kev kuaj mob thiab kev kho mob.

Cov mis mos molecular ntawm Edotreotide yog C₆₅H₉₂N₁₄O₁₈S₂, nrog rau qhov hnyav molecular ntawm kwv yees li 1421.64 (variations yuav tshwm sim vim purity los yog npaj tej yam kev mob nyob rau hauv ntau qhov chaw). Nws cov qauv yog tsim los ntawm kev sib xyaw ua ke ntawm DOTA (peptide cross-tus neeg sawv cev txuas) thiab Tyr³-Octreotide (ib qho somatostatin analogue), uas ua rau muaj kev sib txuam ruaj khov. Cov qauv cyclic no yog tswj hwm los ntawm disulfide daim ntawv cog lus tsim los ntawm ob lub cysteine, uas yog qhov tseem ceeb rau nws qhov tshwj xeeb khi rau lub hom phiaj receptor. N-terminal ntawm Edotreotide peptide saw muaj ntau pawg carboxyl functional, thiab N-terminal nws tus kheej yog ib pawg cawv hydroxyl functional. Lub xub ntiag ntawm cov pab pawg ua haujlwm no ua rau nws muaj qee yam tshuaj lom neeg kev ua si thiab reactivity.

Edotreotide feem ntau tshwm sim ua dawb los tawm - cov hmoov dawb ntawm chav tsev kub. Nws muaj solubility zoo thiab muaj peev xwm yaj nyob rau hauv feem ntau cov organic solvents, xws li dimethyl sulfoxide (DMSO), thiab dej. Cov cuab yeej no ua rau Edotreotide tau yooj yim tsim rau hauv cov kev xav tau kev daws teeb meem rau kev tshawb fawb hauv chav kuaj thiab kev siv tshuaj kho mob.

Cov tshuaj stability ntawm Edotreotide yog cuam tshuam los ntawm ntau yam, xws li kub, lub teeb raug, av noo, thiab kev xaiv ntawm hnyav. Thaum lub sijhawm khaws cia, txhawm rau tswj nws cov tshuaj lom neeg ruaj khov thiab kev ua haujlwm lom neeg, Edotreotide hmoov yuav tsum tau muab kaw thiab khaws cia ntawm qhov kub ntawm -20 degree, zam lub teeb thiab noo noo. Yog tias nws tau npaj los ua kev daws teeb meem, nws yuav tsum tau muab tshem tawm kom tsis txhob rov ua kom khov thiab thawing, uas tuaj yeem ua rau nws cov qauv thiab kev ua haujlwm. Ntawm -80 degree, cov tshuaj Edotreotide tuaj yeem khaws cia rau ob peb lub hlis; thaum nyob rau ntawm -20 degree, lub sij hawm cia yog luv dua.

 

Ib qho ntawm cov tshuaj lom neeg zoo kawg li ntawmEdotreotideyog nws lub peev xwm los khi nrog ntau yam xov tooj cua isotopes, tsim cov affinity tracers los yog cov tshuaj kho mob. Piv txwv li, Edotreotide tuaj yeem khi nrog gallium-68 (⁶⁸Ga), tsim ⁶⁸Ga-Edotreotide, uas yog tus kws kho mob zoo PET. Tom qab txhaj tshuaj, ⁶⁸Ga-Edotreotide tuaj yeem tshwj xeeb khi rau somatostatin receptors (SSTR) ntawm qhov chaw ntawm cov qog hlwb neuroendocrine, tshwj xeeb tshaj yog cov SSTR2 subtype, yog li qhia meej qhov chaw, qhov loj me thiab metastasis ntawm cov qog hauv PET scans.

 

Tsis tas li ntawd, Edotreotide kuj tuaj yeem ua ke nrog cov tshuaj radioactive nuclides (xws li yttrium-90 (⁹⁰Y), lutetium-177 (¹⁷⁷Lu))) los tsim cov tshuaj radiopharmaceutical conjugates (RDCs). Cov tshuaj no tuaj yeem tsom thiab xa cov xov tooj cua nuclides mus rau SSTR-zoo qog hlwb, tso beta rays los ua kom apoptosis ntawm cov qog hlwb, yog li ua tiav kev kho mob.

Kev ua haujlwm lom neeg ntawm Edotreotide feem ntau yog los ntawm nws txoj kev sib raug zoo siab khi rau somatostatin receptors. Somatostatin receptors tau qhia ntau heev nyob rau saum npoo ntawm ntau yam neuroendocrine qog hlwb. Tom qab mus txog qhov chaw qog los ntawm cov hlab ntsha, Edotreotide tshwj xeeb khi rau SSTR los ntawm nws cov qauv cyclic tshwj xeeb. Tom qab kev khi, nws tuaj yeem ua rau muaj kev hloov pauv hauv cov txheej txheem ntawm intracellular signaling pathways, xws li inhibiting adenylate cyclase kev ua thiab txo cov tsim ntawm cyclic adenosine monophosphate (cAMP), yog li inhibiting cov metabolism, proliferation, thiab sib txawv ntawm cov qog hlwb thiab ua tiav lub hom phiaj ntawm inhibiting qog loj hlob.

Edotreotideyog ib qho kev xaiv ligand uas tsom mus rau somatostatin receptor 2 (SSTR2). Nws cov txheej txheem ntau lawm suav nrog cov tshuaj lom neeg sib xyaw ua ke thiab cov txheej txheem xov tooj cua. Cov ntaub ntawv hauv qab no qhia txog kev tsim khoom los ntawm tsib yam: xaiv cov khoom siv raw, cov txheej txheem sib xyaw ua ke, kev tswj kom zoo, cov ntawv xov tooj cua, thiab kev tsim tawm.

 

Kev xaiv raw khoom

 

Lub synthesis ntawm Edotreotide pib nrog meej piv ntawm ntau yam amino acids, ntawm cov glycine thiab phenylalanine yog cov khoom tseem ceeb. Cov amino acids no yuav tsum ua kom tau raws li cov qauv purity siab kom ntseeg tau tias kev ua haujlwm lom neeg ntawm cov khoom kawg. Tsis tas li ntawd, thaum lub sij hawm tsim cov txheej txheem, tus neeg sawv cev hlau chelating, DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), yog siv. Nws tuaj yeem tsim cov chaw ruaj khov nrog cov xov tooj cua isotopes, muab lub hauv paus rau cov ntawv xov tooj cua ntawm Edotreotide.

Synthesis cov kauj ruam

 

Amino acid condensation

Raws li cov tshuaj tiv thaiv nruj, cov amino acids xaiv tau raug rau cov tshuaj tiv thaiv condensation nyob rau hauv ib qho molar ratio. Cov kauj ruam no yuav tsum muaj kev tswj xyuas qhov kub thiab txias, pH tus nqi, thiab lub sijhawm tshuaj tiv thaiv kom ntseeg tau tias cov amino acids raug txuas mus rau cov saw peptide.

Cov tshuaj tiv thaiv condensation feem ntau yog ua los ntawm cov khoom siv -theem synthesis txoj kev, uas tsim cov peptide saw kauj ruam los ntawm kev maj mam ntxiv cov amino acids thiab tshem tawm cov pab pawg tiv thaiv. Cov khoom siv-theem synthesis txoj kev muaj qhov zoo ntawm kev ua haujlwm yooj yim thiab cov khoom lag luam siab.

Kev tiv thaiv thiab cyclization

Tom qab peptide saw synthesis tiav, cov pab pawg tiv thaiv yuav tsum tau muab tshem tawm kom nthuav tawm cov chaw reactive. Cov kauj ruam no feem ntau yog ua los ntawm kev siv cov tshuaj reagents tshwj xeeb hauv cov mob me me kom tsis txhob ua rau cov saw peptide puas.

Tom qab ntawd, cov tshuaj tiv thaiv cyclization yog nqa tawm los tsim cov qauv cyclic ruaj khov ntawmEdotreotide. Cov tshuaj tiv thaiv cyclization feem ntau yog ua los ntawm kev siv oxidants los yog cross- txuas cov neeg ua hauj lwm los tsim cov ntawv cog lus disulfide lossis lwm cov ntawv cog lus covalent ntawm cov haujlwm tshwj xeeb hauv cov saw peptide, yog li txhim kho cov qauv saw peptide.

Purification thiab desalting

Cov khoom nyoos Edotreotide tom qab synthesis yuav tsum tau ua kom huv huv cov kauj ruam kom tshem tawm cov impurities thiab cov khoom siv tsis zoo. Cov txheej txheem purification feem ntau suav nrog siab -kev ua haujlwm ua kua chromatography (HPLC), ion pauv chromatography, thiab lwm yam.

Cov khoom purified kuj yuav tsum tau mus rau kev kho mob desalting kom tshem tawm cov ntsev seem thiab lwm yam me me molecule impurities. Desalting kev kho mob feem ntau yog ua los ntawm kev siv xws li kev lim ntshav, ultrafiltration, los yog gel filtration.

Cim npe nrov: Tuam Tshoj edotreotide manufacturers, lwm tus neeg