Etelcalcetide

Etelcalcetide API

Etelcalcetidendi buku, lopangidwacalcimimetic peptidekuvomerezedwa kuchizahyperparathyroidism yachiwiri (SHPT)mwa odwala akuluakulu omwe ali ndimatenda a impso (CKD)kulandirahemodialysis. SHPT ndi vuto lodziwika bwino komanso lalikulu la matenda a aimpso omaliza, omwe amayamba chifukwa cha kusokonezeka kwa calcium, phosphorous, ndi vitamini D metabolism. Kulimbikira kukwera kwamahomoni a parathyroid (PTH)zingayambitse kuaimpso osteodystrophy, vascular calcification, matenda a mtima, ndi kuwonjezeka kwa imfa.

Etelcalcetide imapereka anjira yolunjika, yopanda opaleshonikuwongolera milingo ya PTH mwa odwala dialysis, omwe akuyimira calcimimetic ya m'badwo wachiwiri ndizabwino zosiyanapamankhwala amkamwa monga cinacalcet.

Njira Yochitira

Etelcalcetide ndisynthetic peptide agonistchacalcium-sensing receptor (CaSR), yomwe ili pamwamba pa maselo a parathyroid. Imatsanzira zochita za calcium ya extracellular ndi allosterically activating CaSR, potero:

• Kuchepetsa kutulutsa kwa hormone ya parathyroid (PTH).

• Kuchepetsa kuchuluka kwa calcium ndi phosphorous mu seramu

• Kupititsa patsogolo calcium-phosphate homeostasis

• Kuchepetsa chiopsezo cha kusinthika kwa mafupa ndi kuwerengetsa kwamtima

Mosiyana ndi oral calcimimetics, Etelcalcetide imayendetsedwakudzera m'mitsemphapambuyo pa hemodialysis, yomwe imathandizira kutsata kwamankhwala ndikuchepetsa zotsatira zoyipa za m'mimba.

Kafukufuku wa Zachipatala ndi Kuchita Bwino

Etelcalcetide yawunikidwa m'mayesero angapo azachipatala a Phase 3, kuphatikizamaphunziro awiri ofunika kwambiri osasinthikalofalitsidwa muThe LancetndiNew England Journal of Medicine. Maphunzirowa adakhudza odwala opitilira 1000 a hemodialysis omwe ali ndi SHPT yosalamulirika.

Zotsatira zazikulu zachipatala ndi izi:

• Kuchepetsa kofunikira pamilingo ya PTH(> 30% mwa odwala ambiri)

• Kuwongolera kwapamwamba kwaseramu phosphorous ndi calcium-phosphate mankhwala (Ca × P)

• Chiwopsezo chokulirapo cha mayankho a biochemicalpoyerekeza ndi cinacalcet

• Kutsatiridwa bwino kwa odwalachifukwa cha makonzedwe a pambuyo pa dialysis IV katatu pa sabata

• Kuchepetsa zizindikiro za kusintha kwa mafupa(mwachitsanzo, fupa la alkaline phosphatase)

Zopindulitsa izi zimathandizira Etelcalcetide ngati ajekeseni woyamba wa calcimimetickuyang'anira SHPT mwa odwala dialysis.

API Kupanga ndi Ubwino

ZathuEtelcalcetide APIamapangidwa kudzerasolid-phase peptide synthesis (SPPS), kuonetsetsa kuti zokolola zambiri, zoyera, ndi kukhazikika kwa maselo. API:

• Zimagwirizana ndi zolimbaMiyezo ya GMP ndi ICH Q7

• Ndioyenera kugwiritsidwa ntchito mkatijekeseni mankhwala mankhwala

• Amayesedwa mokwanira, kuphatikiza HPLC, zosungunulira zotsalira, zitsulo zolemera, ndi milingo ya endotoxin.

• Ikupezeka muoyendetsa ndi kupanga malonda masikelo

Kuthekera Kwachire ndi Ubwino Wake

• Non-hormonal mankhwalakwa SHPT mwa odwala CKD pa dialysis

• Njira ya IV imatsimikizira kutsata, makamaka kwa odwala omwe ali ndi kulemedwa kwa mapiritsi kapena kusalolera kwa GI

• Zingathandize kuchepetsazovuta zanthawi yayitalimatenda a mineral and bone (CKD-MBD)

• Zimagwirizana ndi zomangira phosphate, ma analogi a vitamini D, ndi chisamaliro chokhazikika cha dialysis