Larazotide, e nyane ya molomo, peptide ea maiketsetso le mohanyetsi ea khethang oa zonulin e fapane le lithethefatsi tse ling kaha motsoako ona ha o tlame li-receptor per se.
E sebetsa ho motlatsi karolo (e nkiloeng lingoliloeng le puisanong ea botho) ka ho tloaeleha mokoallo o sa sebetseng oa mala o bonoang bonyane lefu la celiac.
Larazotide e thibela ho buleha ha gluten-mediated tight junction and ke pheko e ntle e sa jeng lijo bakeng sa bakuli ba CD ba ka tlase ho a. GFD.
Larazotide e bontšitse katleho e ts'episang ntlafatsong ea bongaka lithutong tsa Phase IIb, haholo bakeng sa matšoao a sa foleng.
Ntle le ts'ebeliso ea eona e ka sehloohong mafung a gastrointestinal, Lithuto tsa pele tsa in vitro li bonts'itse ts'ebetso ea antiviral ea Larazotide khahlano le varicella-zoster kokoana-hloko (VZV), ho lebisa lits'ebetsong tse ncha tsa lefu le tšoaetsanoang.
Lefapheng la meriana, Larazotide ke katleho e kholo ea molomo ea peptide.
Ho monya ka molomo ha lithethefatsi tse tloaelehileng tsa peptide ho bonts'itsoe "ho fokola hobane li senngoa ke li-enzyme tsa GI..
Sebopeho sena se secha se e lumella ho sebetsa ho sepheo sa mala sebakeng sa heno ka mokhoa o fokolang oa ho monya, ka hona ho fokotsa litla-morao life kapa life tse ka bang teng tsa systemic.
Tatelano
H-Gly-Gly-Val-Leu-Val-Gln-Pro-Gly-OH
Nomoro ea CAS
258818-34-7
Foromo ea limolek'hule
C32H55N9O10
Boima ba Molek'hule
725.83
Lipatlisiso tsa Larazotide
1.Boitsebiso ba Sepheo le Moralo oa Lithethefatsi
Zonulin, protheine e laolang mala a manyane (LE) paracellular permeability in a reversible and inducible feshene e ile ea sibolloa.
Leha ho le joalo mokgoa wa ketso ea Larazotide e tšoana le AT-1001 eo–ke ho re, thibelo ea zonulin e tlamang ho receptor ea eona le ka thibelo ena ea ho eketseha ha mala ka ho thibela zonulin ho tloha makopano a tiileng-, e ile ea lekoa e le modulator ea pele ea TJ bathong.
Leha ho le joalo, ka lebaka la tatellano ea eona e ikhethang ea amino acid le motsoako oa letsoai la acetate (Larazotide acetate, Nomoro ea CAS 881851-50-9), Larazotide [Ac-KPFSLSQ(Cys)] e bonts'a botsitso bo phahameng le bioavailability ea lehae ka maleng.
2.Ho feto-fetoha ha mosebetsi oa Intestinal Barrier
Larazotide e na le boleng bo tebileng ba saense e le mokhoa o mocha le o matla oa ho feto-fetoha ha 'mele oa mala..
Ketso ea eona e sebelisoa haholo ka ho ba "analogue ea sebopeho sa zonulin, ho qothisana lehlokoa le zonulin bakeng sa ho tlama li-receptors holim'a leseli la li-enterocyte.
Sena se lebisa ho thibelo ea ts'ebetso ea intracellular myosin light-chain kinase (MLCK), ho hlophisoa bocha ha cytoskeletal le disassembly ea liprotheine tse thata tsa junction ho kenyelletsa ZO-1.
Ka mokhoa ona oa limolek'hule, Larazotide e boloka tšitiso ea "tšitiso" ea likhohlano tse thata 'me e thibela phetisetso e sa batleheng. macromolecules mohlala, gliadin.
3.Tsamaiso ea Lefu la Celiac
Lefu la Celiac (CD) ke lefu la autoimmune enteropathy, e qalileng ke ho pepesehela gluten ho batho ba nang le tšekamelo ea liphatsa tsa lefutso, mme e ama hoo e ka bang 1% ea baahi ba lefatše lohle.
Hajoale, ho khomarela lijo tse se nang gluten ke eona feela phekolo e netefalitsoeng.
Leha ho le joalo, ho khomarela nako e telele lijong ho thata; ho qoba ka tieo ho kopana ho ka ba thata ho fihlella mme matšoao a ntse a tsoela pele ho bakuli ba bangata.
Ntlheng ea eona, MOA ea Larazotide ka lefu la celiac ke thibelo e khethehileng ea ho bula TJ e entsoeng ka zonulin..
Ka lefu la celiac, karabelo ea li-peptide tse shoeleng tsa gliadin, enterocyte CXCR3 e kopanela e lebisang ho lokolloeng zonulin.
Joale zonulin ea mahala e sebelisana le receptor ea eona lera la epithelial, ho etsa hore ho be le litsela tsa matšoao a intracellular tse lebisang ho phosphorylation ea khanya ea myosin.
Sena se fella ka ho fallisoa - ha liprotheine tse kopaneng (joalo ka ZO-1, ocludin le claudins) le cytoskeleton ho hlophisoa bocha ka lebaka la ntlafatso ea ho kenella ha mala.
Larazotide ke mohanyetsi oa tlholisano oa octapeptide, ka tlholisano le ka mokhoa o tsoileng matsoho ho tlama li-receptor tsa zonulin sebakeng se khanyang sa lisele tsa epithelial., ka hona ho thibela ts'ebetso ena ea matšoao a cascade, le ho boloka thibelo ea homeostasis.
Teko ea bohlokoa ea Phase IIb e kenyellelitsoe 342 bakuli ba nang le matšoao a tsoelang pele boemong ba GFD.
Tekanyo ea 0.5 mg makhetlo a mararo ka letsatsi e bonts'itsoe e sebetsa ebile e phahametse placebo mabapi le phokotso ea matšoao a ka mpeng ka ts'ireletso e amohelehang le boemo ba mamello pele ho thuto e tsoelang pele..
4.Thepa ea Antiviral
Ntle le ts'ebeliso ea eona ka maleng ho ruruha, Larazotide e tšoaile in vitro antiviral efficacy khahlanong le VZV.
Tlhahiso ena e eketsa bokhoni ba eona ba kalafo mme e bonts'a mekhoa e fapaneng ea ts'ebetso e kanna ea sebetsa..
Bopaki ba in vitro bo bontša hore Larazotide e thibela ho pheta-pheta ha VZV OKA le 07-1 mathata le EC₅₀ ea 44.14 μM le 59.06 μM, ka ho latellana.
Boemo bona ba ts'ebetso bo itekanetse bakeng sa moemeli oa antiviral.
Leha ho le joalo, kaha ts'ebetso ea Larazotide e fumaneha sebakeng se batlang se le seholo fensetere ea phekolo, sena se eketsa bohlokoa bo boholo kholong ea bongaka.
Ka ho khetheha, the cytotoxicity ea moemeli ona liseleng tse amohelang batho (Lisele tsa Vero) bontshitse a CC₅₀ boleng ba 82.5 μM, ho fana ka tekanyo ea TI ea ~ 1.4–1.9.
Sena se fana ka maikutlo a mokhoa o itekanetseng empa o amohelehang oa tšireletso maemong a antiviral a sebetsang hantle..
COA
HPLC
MOF
