Larazotide, obere ọnụ, peptide sịntetik na onye na-emegide ahọpụtara nke zonulin dị iche na ọgwụ ndị ọzọ n'ihi na ngwakọta a anaghị ejikọta onye ọ bụla na-anabata ya.
Ọ na-arụ ọrụ na a adjuvant ọrụ (sitere na akwụkwọ na nkwurịta okwu nkeonwe) site na ịhazi ihe mgbochi eriri afọ na-adịghị arụ ọrụ nke a na-ahụ ma ọ dịkarịa ala na ọrịa celiac.
Larazotide na-egbochi mmeghe oghere nke na-eme ka gluten na-eme ka ọ bụrụ ọgwụgwọ na-adịghị eri nri maka ndị ọrịa CD n'okpuru a GFD.
Larazotide egosila ịdị mma na-ekwe nkwa na mmepe ụlọ ọgwụ na ọmụmụ nke Phase IIb, karịsịa - maka mgbaàmà na-adịghị ala ala.
Na mgbakwunye na ngwa ya bụ isi na ọrịa eriri afọ, ọmụmụ ihe izizi in vitro egosila ọrụ antiviral nke Larazotide megidere varicella-zoster nje (VZV), na-eduga ngwa ngwa ọhụrụ nwere ike ibute ọrịa na-efe efe.
Na ngalaba nke ọgwụ, Larazotide bụ nnukwu ọgwụgwọ ọgwụgwọ peptide ọnụ.
Egosiputara mmịnye ọnụ nke ọgwụ peptide a na-emekarị ka ọ dị njọ n'ihi na GI enzymes na-emebi ha..
Nhazi ọhụrụ a na-enye ya ohere ịrụ ọrụ na ebumnuche eriri afọ na mpaghara yana obere mmịpụta usoro, si otú ahụ ibelata mmetụta ọ bụla nwere ike ime n'usoro.
Usoro
H-Gly-Gly-Val-Leu-Val-Gln-Pro-Gly-OH
Nọmba CAS
258818-34-7
Usoro ihe omimi
C32H55N9O10
Ibu molekụla
725.83
Nnyocha nke Larazotide
1.Nchọpụta ebumnuche na imepụta ọgwụ
Zonulin, protein na-edozi ahụ obere eriri afọ (NA) paracellular permeability na a reversible na enweghi ike ime ihe achọpụtara ejiji.
Ọbụna ma ọ bụrụ na ụdị omume Larazotide dị ka AT-1001–ya bu ikwu, Mgbochi nke zonulin na-ejikọta ya na onye na-anabata ya na site na mgbochi a nke mmụba nke eriri afọ site na attenuation nke zonulin. nkwụsịtụ siri ike-, a nwalere ya dị ka ihe mbụ TJ modulator n'ime mmadụ.
Agbanyeghị, N'ihi usoro amino acid ya dị iche na nhazi nnu acetate (Larazotide acetate, CAS Mba 881851-50-9), Larazotide [Ac-KPFSLSQ(Cys)] na-egosipụta nkwụsi ike dị elu na bioavailability mpaghara na eriri afọ.
2.Mgbanwe nke Ọrụ mgbochi eriri afọ
Larazotide na-ejide uru sayensị miri emi dị ka ụzọ ọhụrụ na ike siri ike maka ngbanwe kpọmkwem nke mgbochi eriri afọ..
A na-eme ihe omume ya site na ịbụ analog nke zonulin, na-asọ mpi zonulin maka ijikọ ndị na-anabata ya n'elu luminal nke enterocytes.
Nke a na-eduga na mgbochi nke intracellular-arụ ọrụ nke myosin light-chain kinase (MLCK), nhazigharị cytoskeletal na igbasa protein njikọ siri ike gụnyere SE-1.
Site na usoro mkpụrụ ndụ ihe nketa a Larazotide na-echekwa ihe mgbochi-iguzosi ike n'ezi ihe nke njikọ siri ike ma gbochie ntụgharị nke achọghị. macromolecules eg., gliadin.
3.Nlekọta nke Ọrịa Celiac
Ọrịa Celiac (CD) bụ autoimmune enteropathy, malitere site na ikpughe na gluten n'ime ndị nwere ọrịa mkpụrụ ndụ ihe nketa, na ọ na-emetụta banyere 1% nke ndị bi n'ụwa niile.
Ugbu a, ịgbaso nri na-enweghị gluten bụ naanị ọgwụgwọ egosipụtara.
Agbanyeghị, ogologo oge na-agbaso nri nri siri ike; ịzere nzuzo nke kọntaktị nwere ike isi ike nweta yana mgbaàmà na-adịgide n'ọtụtụ ndị ọrịa.
Na isi ya, MOA nke Larazotide na ọrịa celiac bụ ihe mgbochi nke zonulin na-ebute TJ oghere..
Na ọrịa celiac, Nzaghachi nke gliadin peptides deamidated, ọrịa enterocyte CXCR3 na-arụ ọrụ na-eduga na mwepụta nke zonulin.
Zonulin efu na-emekọrịta ihe na onye na-anabata ya na oyi akwa epithelial, na-ebute ụzọ mgbaàmà intracellular nke na-eduga na phosphorylation myosin light-chain.
Nke a na-ebute mweghachi - nke protein njikọ siri ike (dị ka ZO-1, occludin na claudins) na cytoskeleton nhazigharị site na nkwalite nke permeability nke eriri afọ.
Larazotide bụ onye na-emegide octapeptide na-asọmpi, na-asọmpi na ngbanwe na-ejikọ ndị na-anabata zonulin n'elu luminal nke mkpụrụ ndụ epithelial., si otú a na-egbochi usoro nrịbama cascade a, ma na-edobe ihe mgbochi homeostasis.
Ọnwụnwa ụlọọgwụ nke agba nke IIb gụnyere 342 ndị ọrịa nwere mgbaàmà na-aga n'ihu na ntọala nke GFD.
Otu dose nke 0.5 mg ugboro atọ kwa ụbọchị ka egosiri na ọ dị irè ma dị elu karịa placebo n'ihe gbasara mbelata nke eriri afọ na profaịlụ nchekwa na nnabata nnabata tupu ọmụmụ ihe ọzọ..
4.Njirimara Antiviral
Ewezuga ngwa ya na eriri afọ mbufụt, Larazotide egosila na vitro dị irè antiviral megide VZV.
Nchọpụta a na-agbatị ikike ọgwụgwọ ya ma na-egosi usoro mmemme dị iche iche nwere ike ịdị na-arụ ọrụ..
Ihe akaebe in vitro na-egosi na Larazotide na-egbochi mmegharị nke VZV OKA na 07-1 nsogbu na EC₅₀ nke 44.14 μM na 59.06 μM, n'otu n'otu.
Ọkwa ọrụ a dị oke maka onye na-ahụ maka ọgwụ nje.
Agbanyeghị, dị ka ọrụ Larazotide na-arụ ọrụ nke ukwuu windo ọgwụgwọ, nke a na-agbakwunye na nnukwu uru - mmepe ụlọ ọgwụ.
Karịsịa, nke cytotoxicity nke onye nnọchi anya a na sel nnabata (Mkpụrụ ndụ Vero) gosiputara a CC₅₀ uru nke 82.5 μM, na-enye oke TI nke ~ 1.4-1.9.
Nke a na-egosi ihe nchekwa dị obere mana enwere ike ịnakwere na mkpokọta antiviral - nke dị irè.
COA
HPLC
MS
