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1 kits (10 Vials)
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▎ Abaloparatide Tsarin
Source: PubChem |
Jeri: AVSEHQLLHDKGKSIQDLRRRELLEKLLXKLHTA Tsarin kwayoyin halitta: C 174H 300N 56O49 Nauyin Kwayoyin: 3961 g/mol Lambar CAS: 247062-33-5 Saukewa: 76943386 Ma’ana: Tymlos; BA058; BIM-44058 |
▎ Abaloparatide Binciken
Menene asalin binciken abaloparatide?
Osteoporosis cuta ce ta tsarin kwarangwal na yau da kullun wanda ke da ƙarancin ƙasusuwa da lalacewar nama na ƙashi. Wannan yana haifar da ƙarar ƙasusuwan ƙashi da sauƙi ga karaya, tare da raunin hip da kashin baya ya zama sakamako na kowa. Yana tasiri sosai ga ingancin rayuwar marasa lafiya kuma yana ƙara nakasa da adadin mace-mace. Tare da haɓaka yawan tsufa na duniya, abubuwan da ke faruwa na osteoporosis na ci gaba da karuwa. An kiyasta cewa 42% -56% na mata da 27% -29% na maza sama da shekaru 50 za su fuskanci karayar osteoporotic, yana mai da shi batun lafiyar jama'a na gaggawa. Maganin osteoporosis na al'ada, irin su bisphosphonates da masu haɓaka masu karɓar isrogen receptor (SERMs), da farko suna kula da ƙasusuwan kashi ta hanyar hana haɓakawar kashi na osteoclast. Duk da haka, ingancin su yana iyakance ga marasa lafiya tare da raguwar ƙashi mai tsanani da haɗari mai girma. Ko da yake parathyroid hormone (PTH) 1-34 gutsuttsura (teriparatide) shi ne na farko anabolic wakili yarda da Amurka Abinci da Drug Administration (FDA), yadda ya kamata kara da yawa yawa kashi da kuma rage karaya hadarin, da dogon lokacin amfani da shi yana dauke da gazawar ciki har da inganta kashi resorption, hypercalcemia, da kuma yiwuwar kara hadarin osteosarcoma.
A kan wannan bayanan, haɓaka sabbin magunguna waɗanda ke haɗa tasirin anabolic masu ƙarfi yayin guje wa waɗannan abubuwan da ke da alaƙa yana da mahimmanci. A matsayin analog na peptide hormone parathyroid (PTHrP), abaloparatide yana riƙe da aikin anabolic mai ƙarfi yayin da yake rage tasiri akan resorption na kasusuwa da kuma rage sauye-sauyen ƙwayoyin calcium, yana mai da amfani ga osteoporosis.
Menene hanyoyin aiwatar da abaloparatide?
Yin hulɗa tare da Parathyroid Hormone Receptor 1 (PTH1R)
Rarraba Zaɓar Mai karɓa: Abaloparatide shine zaɓi na agonist na mai karɓar hormone parathyroid 1 (PTH1R). PTH1R an bayyana shi sosai a saman sel a cikin kyallen takarda kamar kashi da koda, suna taka muhimmiyar rawa wajen daidaita metabolism na kashi. Abaloparatide musamman yana ɗaure zuwa PTH1R, yana farawa da jerin hanyoyin siginar siginar intracellular don daidaita metabolism na kashi. Bayan ɗaure, yana kunna adenylate cyclase, yana haɓaka samar da AMP na cyclic na ciki (cAMP) don daidaita aikin salula da metabolism [1,2].
Bambance-bambance daga sauran ligands: Parathyroid hormone (PTH) da kuma parathyroid hormone-related protein (PTHrP) kuma sun ɗaure zuwa PTH1R. Kodayake PTH, PTHrP, da Abaloparatide duk sigina ta hanyar PTH1R, hanyoyin siginar su na ƙasa sun bambanta. PTH da PTHrP suna nuna alaƙa iri ɗaya don R^G (GTPγS-sensitive) jihar PTH1R. Teriparatid (TPTD, watau, 1-34 PTH) yana da kusanci sau huɗu mafi girma ga jihar R^0 (GTPγS-marasa fahimta) fiye da PTHrP, yana haifar da siginar CAMP mai tsawo wanda TPTD ya jawo. Sabanin haka, abaloparatide, wanda aka samo daga PTHrP (1-34), an ƙera shi don ingantaccen kwanciyar hankali kuma yana shawo kan batutuwa kamar asarar taga anabolic da hypercalcemia hade da amfani da TPTD. Saboda ƙimar rarrabawar PTHrP-PTH1R ya fi sauri fiye da na PTH-PTH1R, tasirin osteogenic na PTHrP yana tare da ƙarancin sha da hypercalcemia fiye da TPTD. Abaloparatide ya gaji wannan fa'idar dangi [1,2,3].
Ka'idar Tattalin Arziki na Kashi
Inganta Osteogenesis: Abaloparatide yana ƙarfafa ayyukan osteoblast, haɓaka haɓakawa da ƙaddamar da matrix na kasusuwa don haɓaka haɓakar kashi. Osteoblasts suna haɗawa da ɓoye abubuwan haɗin matrix na kasusuwa kamar collagen da osteocalcin, waɗanda sannu a hankali suna yin ma'adinai don samar da sabon nama na kashi. Nazarin ya nuna cewa a cikin zalunta postmenopausal osteoporosis, abaloparatide yana ƙaruwa da yawa na ma'adinai (BMD) a wuraren da suka hada da jimlar hip, wuyan mata, da kashin baya na lumbar. Ta hanyar ƙarfafa furcin kwayoyin halittar da ke da alaƙa da osteoblast, yana haɓaka haɓakar ƙwayoyin sunadarai masu mahimmanci kamar osteocalcin da nau'in collagen I. Wannan yana haɓaka kauri na trabecular da ƙarfafa cortical, haɓaka ƙarfin skeletal da inganci yayin rage haɗarin karaya [1,2,3].
Inhibition of Bone Resorption: While Abaloparatide primarily acts as an anabolic agent, it also exhibits some inhibitory effects on bone resorption. Yana daidaita bambance-bambance da aiki na osteoclasts-kwayoyin da ke da alhakin resorption na kashi wanda ke narkar da ma'adinai na kasusuwa da matrix na kwayoyin halitta ta hanyar sakin abubuwan acidic da enzymes proteolytic. Abaloparatide na iya rage yawan resorption na kashi ta hanyar rage bambance-bambancen osteoclast precursor sel zuwa manyan osteoclasts ko rage tsawon rayuwar balagaggen osteoclasts. A lokaci guda, yana daidaita sigina tsakanin osteoblasts da osteoclasts, yana kiyaye daidaito mai ƙarfi tsakanin samuwar kashi da resorption. Misali, yana rage kunnawar osteoclast da ayyukan resorptive ta hanyar rage mai kunnawa mai ɓoye sirri na osteoblast na κB ligand (RANKL). Ba kamar teriparatide ba, abaloparatide baya haɓaka samar da RANKL sosai, don haka yana hana asarar taga anabolic wanda ke faruwa lokacin da resorption ya mamaye samuwar a cikin matakai na gaba [1,2,3].
Hoto 1 Model na parathyroid hormone (PTH) / teriparatide da PTH mai alaka da peptide (PTHrP / abaloparatide kunnawa na parathyroid hormone irin 1 mai karɓa (PTH1R)) [4].
Tasirin Gurasa Jiki (a cikin Nazarin da ke da alaƙa da Osteoarthritis)
Yana Haɓaka Ƙwararrun Matrix Synthesis: Nazarin a cikin osteoarthritis (OA) sun nuna cewa abaloparatide yana yin tasiri mai kariya akan guringuntsi. Articular chondrocytes suna bayyana PTH1R, kuma Abaloparatide yana kunna wannan mai karɓa, yana ƙarfafa chondrocytes don haɗa abubuwan da ke cikin matrix na guringuntsi. Misali, binciken ya nuna Abaloparatide yana haɓaka magana mai lubricin (Prg4), wani muhimmin furotin matrix na waje a cikin guringuntsi wanda ke da mahimmanci don kiyaye lubrication na haɗin gwiwa da rage gogayya. Hakanan yana haɓaka haɓaka nau'in collagen na II, babban ɓangaren matrix na guringuntsi, wanda ke taimakawa kiyaye tsarin guringuntsi da amincin aiki. Ta hanyar haɓaka haɓakar waɗannan abubuwan haɗin gwiwar guringuntsi matrix, Abaloparatide yana taimakawa wajen gyarawa da kare ƙwayoyin guringuntsi da suka lalace, yana rage jinkirin ci gaban osteoarthritis [5].
Hana hypertrophy na chondrocyte da lalata: Abaloparatide na iya kashe tsarin bambancin hypertrophic na chondrocytes. A lokacin ci gaban osteoarthritis, chondrocytes suna fuskantar bambance-bambancen hypertrophic, wanda ke da alaƙa da ƙarar ƙwayar ƙwayar cuta da haɓakar maganganu na takamaiman alamomin hypertrophy irin su nau'in X collagen (Col10). Wannan tsari yana haifar da lalacewa na matrix na guringuntsi da lalatawar guringuntsi. Nazarin ya nuna cewa maganin Abaloparatide yana rage haɓakar maganganun Col10 a cikin ƙwayar guringuntsi yayin da yake rage yawan manyan ƙwayoyin hypertrophic. Wannan yana nuna yana iya rage bambance-bambancen chondrocyte hypertrophic, kula da yanayin chondrocyte na yau da kullun, don haka kare guringuntsi da jinkirta ci gaban osteoarthritis [5].
Menene aikace-aikacen Abaloparatide?
Maganin Osteoporosis
Postmenopausal Osteoporosis: Abaloparatide, mai zaɓaɓɓen agonist na mai karɓa na hormone parathyroid 1 (PTHR1), an nuna shi don magance osteoporosis, musamman a cikin mata masu tasowa a cikin hadarin karaya ko rashin amsa ga wasu hanyoyin kwantar da hankali. Yana da mahimmanci ƙara yawan ma'adinai na kashi kuma yana rage haɗari da haɗari na sababbin kasusuwa na vertebral da wadanda ba na baya ba a cikin matan postmenopausal.
Male Osteoporosis: A cikin binciken Chandler H akan osteoporosis na namiji ta amfani da berayen orchidectomized (ORX berayen, samfurin osteoporosis na namiji), maganin Abaloparatide ya haifar da karuwa mai yawa a cikin BMD wanda aka auna ta hanyar dual-energy X-ray absorptiometry (DXA) da na gefe ƙididdiga, ciki har da lu'u-lu'u na jiki, ciki har da lumbar da aka lissafta a jimlar jiki. femur, da tibia. Ya inganta haɓakar trabecular sosai, ƙarar kashi, da microarchitecture ba tare da ƙara lambobin osteoclast ba. Wannan yana nuna Abaloparatide yana riƙe da fa'idodin warkewa ga osteoporosis na namiji [6].
Jiyya na Osteoarthritis na Post-Traumatic (PTOA): Bayan shigar da PTOA na gwiwa ta hanyar meniscus destabilization (DMM) tiyata a cikin 16-mako-mako-maza C57BL / 6 mice, allurar subcutaneous na 40 μg / kg Abaloparatide (ko saline azaman iko) an gudanar da makonni 2 bayan farawa. An yi nazarin nama a cikin makonni 8. Results showed that compared to the saline-treated group, the Abaloparatide-treated group exhibited reduced DMM-induced articular cartilage loss and preserved tibial surface cartilage tissue. Immunohistochemical bincike ya nuna cewa maganin Abaloparatide ya rage haɓakar nau'in nau'in nau'in X collagen (Col10) a cikin guringuntsi, ƙara yawan lubricin (Prg4) magana a cikin wuraren da ba a ƙayyade ba, kuma ya rage yawan adadin ƙwayoyin hypertrophic. yana ba da shawarar cewa Abaloparatide yana jinkirin bambance-bambancen hypertrophic kuma yana yin tasirin chondroprotective a cikin linzamin kwamfuta na PTOA, yana ba da sabon dabarun warkewa na PTOA [5].
Farfadowar Kashi na Alveolar: Bayan cirewar kashi na alveolar yana da matuƙar hana motsin hakori na gaba (OTM) ko sanyawa. Tan B hadewar biodegradable, bifunctional bioactive calcium phosphate nanoblossoms (NFs) wanda aka ɗora tare da Abaloparatide (ABL), mai suna ABL@NFs. Wannan kayan yana baje kolin sifa mai labule, haɓakar haɓakar ƙwayar cuta, da kyakkyawan yanayin rayuwa. An saki ABL da farko don ɗaukar sel mai tushe, sannan kuma a ci gaba da sakin Ca⊃2;⁺ da PO₄⊃3; Wannan ya sami nasarar dawo da kasusuwan alveolar mai aiki da yanayin jiki da aiki ba tare da lalata OTM ba [7].
Refractory Hypoparathyroidism (HPT): Chamseddin R ya ruwaito wata mace mai shekaru 39 tare da iatrogenic HPT wanda ya kasa cimma matakan al'ada na al'ada na al'ada duk da yawan adadin bitamin D, abubuwan da ake amfani da su na calcium, da recombinant PTH (rPTH) injections. Bayan gudanar da subcutaneous na abaloparatide ta hanyar facin Sauƙi tare da sa ido na kusa da kuma yin allurai na musamman, sinadarin calcium ɗinta ya kasance mai ƙarfi a 9 mg/dL bayan watanni 2. Da watanni 4, ta ci gaba da kiyaye calcium na al'ada na al'ada ba tare da yanayin hypocalcemia ba yayin da a hankali rage yawan calcium na baki da karin bitamin D [3].
Haɓaka Fusion na Spinal: A cikin aikin tiyata na ƙwanƙwasa-thoracic, an yi amfani da abaloparatide don inganta haɗin gwiwa na kashin baya a cikin marasa lafiya tare da tarihin rashin lafiyar mahaifa da kuma aikin tiyata da yawa. Parikh S et al. ya ruwaito wata mata mai shekaru 66 da haihuwa wadda ta fara maganin 80 mcg Abaloparatide kowace rana makonni biyu bayan tiyata don shirin mako 12. Cervical CT scans a cikin watanni 3 da 6 ya nuna kyakkyawar warkar da haɗin gwiwar mahaifa-thoracic ba tare da alamun rashin haɗin gwiwa ba [8].
Kammalawa
Cibiyoyin aikace-aikacen asibiti na Abaloparatide akan maganin osteoporosis. An nuna shi ga matan da suka yi jima'i tare da osteoporosis a babban haɗari mai haɗari ko rashin amsawa ga wasu hanyoyin kwantar da hankali, haɓaka haɓakar ma'adinai na kasusuwa (BMD) da kuma rage haɗarin vertebral da wadanda ba na vertebral ba. Ga namiji osteoporosis, nazarin dabba ya nuna karuwar BMD a wurare masu yawa da kuma inganta ƙananan ƙananan ƙananan kashi, yana nuna yiwuwar warkewa. A cikin cututtukan osteoarthritis na baya-bayan nan, yana rage asarar guringuntsi kuma yana hana chondrocyte hypertrophy don kare guringuntsi. A cikin farfadowar kashi na alveolar, ABL @ NFs kayan da aka ɗora da wannan miyagun ƙwayoyi suna inganta haɓakar kashi, suna ba da bayani don gyaran kashi na baya-bayan nan. Har ila yau, bincike yana goyan bayan amfani da shi a cikin hypoparathyroidism refractory da haɓakar haɗin gwiwa na kashin baya.
Game da Marubuci
Abubuwan da aka ambata a sama duk bincike ne, gyara su kuma Cocer Peptides ne suka haɗa su.
Mawallafin Jaridar Kimiyya
Bin T mai bincike ne a Sashen Chemistry, Jami'ar Peking, ƙware a kan nanomaterials da aikace-aikacen su a cikin injiniyan halittu. Ayyukansa suna mayar da hankali kan ƙira da haɗin gwiwar nanostructures masu aiki don isar da miyagun ƙwayoyi da aka yi niyya da sabunta nama. Tan ya haɗu da wallafe-wallafe da yawa a cikin manyan mujallu na kimiyya, yana ba da gudummawa ga ci gaba a cikin nanomedicine da farfadowa na farfadowa. An jera Bin T a cikin ambaton ambaton [7].
