Amachiza amancinci e-molecule ahlala eyintsika yeshishini lamachiza!
Phantse inkulungwane, amayeza amancinci emolekyuli abe ngumqolo weshishini lamayeza.
Zinenzuzo ebalulekileyo kwimveliso, ukuthutha kunye nokugcinwa, ukuthotyelwa kwesigulane, uluhlu olukhoyo olujoliswe kuyo, i-immunogenicity, kunye nokuqhubeka nokudlala indima ebalulekileyo kunyango lwesigulane.
Inkqubela phambili yetekhnoloji kule minyaka ilishumi idlulileyo yenze ukuba iinkampani ezixuba amayeza zifumane kwaye ziphuhlise ngakumbi nangakumbi iindlela zonyango zemolekyuli ezincinci zokunyanga uluhlu lwezalathisi ezahlukeneyo, kwaye nakwixesha elizayo, iimolekyuli ezincinci ziya kuqhubeka ziyintsika yamachiza onyango, edlala indima ebalulekileyo kunyango loluhlu lwezifo.
Yintoni ichiza lemolekyuli encinci?
Amachiza emolekyuli amancinci achazwa njengayo nayiphi na i-molecular weight organic compound efunyenweyo, eyilwe, kwaye iphuhliswe ukungenelela kwiinkqubo ezithile ze-physiological ngaphakathi kwe-organism. Amachiza amancinci aqhelekileyo e-molecule aquka i-antibiotics (efana ne-penicillin), i-analgesics (efana ne-paracetamol), kunye neehomoni zokwenziwa (ezifana ne-corticosteroids).
Amachiza emolekyuli encinci zezona ntlobo zivunyiweyo zamachiza ukuza kuthi ga ngoku, anamandla okungena ngokukhawuleza kwiinwebu zeseli kunye nokusebenzisana ngokuchanekileyo kunye neethagethi ezithile ngaphakathi kweeseli.
Iimolekyuli ezincinci zinokubangela ukuphendulwa konyango kumzimba womntu ngeendlela ezahlukeneyo. Ezona ntlobo zintathu zixhaphakileyo zezi:
I-Enzyme inhibitors: Iimolekyuli ezincinci zingenelela ekuqhubekeni kwesifo ngokuthintela umsebenzi we-enzyme;
• I-receptors ye-agonists / abachasi: Iimolekyuli ezincinci zisebenzisana neeprotheni ezikhoyo kwi-cell surface ukuze kusebenze okanye kuvimbe i-receptors;
Iimodyuli ze-Ion channel: Iziyobisi ezincinci ze-molecule zinokulawula ukuvulwa kunye nokuvalwa kweendlela ze-ion ukulawula ukungena kunye nokuphuma kwee-ion kunye nokunyanga izifo ezifana nokuxhuzula.
Ezi ndlela zokusebenza zonke zibandakanya ummandla othile kwiprotheni, eyipokotho ebophelelayo okanye indawo esebenzayo yeemolekyuli ezincinci. Ukuphuhliswa kweeamolekyuli ezincinci ngokuqhelekileyo kusekelwe kwithiyori ye-classical lock engundoqo, ehambelana noyilo lweemolekyuli ezincinci ngokusekelwe kwisithuba, i-hydrophobicity, kunye neempawu zombane zepokotho yokubopha, ukwenzela ukuba ibophe ngokufanelekileyo ekujoliswe kuyo kwaye ichaphazele umsebenzi wayo.
Izibonelelo zamachiza amancinci e-molecule
Ngokunyuka kweemodeli zamachiza asakhulayo anje nge-antibodies, unyango lwejini, kunye nonyango lweeseli, amachiza amancinci emolekyuli ayekhe ajongwa njengaphelelwe lixesha, kodwa eneneni, amachiza emolekyuli amancinci asenako ukungaphindi abuyiselwe.
Xa kuthelekiswa nee-agent zebhayoloji, iimolekyuli ezincinci zisenenzuzo ebalulekileyo kwimveliso, ukuthutha, ukuthotyelwa kwesigulane, uluhlu olukhoyo olujoliswe kuyo, i-immunogenicity, kunye nezinye iinkalo.
Iimolekyuli ezincinci zinezakhiwo ezilula, ezinobunzima be-molecular ngokuqhelekileyo abudluli kwi-500 Daltons, kwaye zinokuthi zenziwe ngokwezifiso ukuhlangabezana neemfuno ezithile zonyango;
Ngokuqhelekileyo izinzile kwaye ayifuni iimeko zokugcina ezikhethekileyo ezifana nokubekwa phantsi kweemeko zokushisa eziphantsi; Indlela yokuziphatha emzimbeni idla ngokuqikelelwa kwaye kulula ukuyilawula.
Ukongeza, iimolekyuli ezincinci zinokujikeleza ngokulula kwaye zihambe ngaphakathi kwento ephilayo, zigqithise ukusuka emathunjini ngokuhamba kwegazi ukuya kwindawo yesenzo, zingene kwi-membrane yeseli ukufikelela kwiithagethi ze-intracellular, kwaye zibe nomsebenzi otyebileyo, ozenza zibe yimfuneko kwiinkalo ezahlukeneyo zonyango ezinje. i-oncology, impilo yentliziyo, izifo ezosulelayo, impilo yengqondo, kunye nezifo zemithambo-luvo.
Iimolekyuli ezincinci ziye zaba, zikho, kwaye ziya kuqhubeka ziyintsika yamachiza onyango lweklinikhi kwixesha elidlulileyo, langoku, nakwixesha elizayo.
Kwiminyaka eyi-15 ukuya kwe-20 edlulileyo, inani elikhulu leziyobisi ezincinci ze-molecule ziye zavunywa yi-FDA kwaye zinempembelelo enkulu ekunyamekelweni kwesigulane, kuquka i-Cymbalta yokunyanga ukudakumba kunye nokuxhalaba, i-Viagra yokuphatha i-erectile dysfunction, i-Tagrisso yokujolisa kwi-NSCLC, kunye ne-Eliquis ye-fibrillation ye-atrial kunye ne-anticoagulation.
Ngapha koko, inani lamachiza amatsha emolekyuli amancinci avunyiweyo yi-FDA anyuke ngaphezulu kwe-50% kulo nyaka uphelileyo, kunye ne-34 yamachiza amancinci amancinci avunyiweyo ngo-2023 kwaye angama-21 kuphela ngo-2022. iyonke i-FDA yamkele amachiza amatsha ngo-2023, ebonisa ukuba iimolekyuli ezincinci zisabalulekile ekuqhubeleni phambili kwezempilo.
Kuluhlu oluphezulu lwe-100 lokuthengisa amachiza ngo-2021, bekukho inani elipheleleyo le-45 yamachiza amancinci e-molecule, ebala i-36% yengeniso yokuthengisa iyonke; Kukho i-11 i-molecule encinci ye-anti-tumor iziyobisi eziye zangena kuluhlu lwe-TOP100, kunye nengeniso yokuthengisa i-51.901 yeebhiliyoni zeedola zaseMelika. Ingeniso ephezulu yokuthengisa yi-12.891 yeebhiliyoni zeedola zase-US kwi-lenalidomide; Ngo-2022, intengiso iyonke yamachiza amancinci kwi-10 ephezulu yafikelela kwi-96.6 yeebhiliyoni zeedola zaseMelika, kunye ne-Paxlovid ethengisa ukuya kuthi ga kwi-18.9 yeebhiliyoni zeedola zaseMelika kwihlabathi jikelele, ebonisa ngokupheleleyo ukubanakho kwentengiso yamachiza amancinci.
