Kisspeptin tau tshawb pom hauv xyoo 1996. Nws lub cev tseem ceeb tau tshwm sim thaum cov kws tshawb fawb pom tias kisspeptin ua haujlwm los ntawm kev khi rau thiab ua kom nws cov receptor, KISS1R. KISS1R signaling pathway yog suav tias yog ib qho tseem ceeb ntawm kev tswj hwm ntawm lub hypothalamic-pituitary-gonadal axis.
Cov kev tshawb fawb tau pom tias kev tswj hwm tas li ntawm kisspeptin tuaj yeem rov ua kom lub cev tsis muaj zog ntawm cov tshuaj hormone luteinizing, tawm tswv yim tias KISS1R sab saud tuaj yeem yog lub hom phiaj zoo dua rau kev kho cov kab mob ntawm cov menyuam yaus. Kev tswj hwm ntawm KP-10 tau pom tias muaj txiaj ntsig zoo hauv kev kho cov kab mob kev ua me nyuam hauv cov qauv tsiaj, tab sis qhov no endogenous ligand tau yooj yim metabolically degraded. Yog li ntawd, kev txhim kho ntawm cov agonists zoo dua thiab ruaj khov rau KISS1R yog qhov kev tshawb fawb tam sim no. Txhawm rau kov yeej qhov kev puas tsuaj thiab tshem tawm sai sai ntawm kisspeptin hauv lub cev, cov kws kho mob tau tsim kisspeptin-10 analogs xws li TAK-448. Cov tebchaw no nthuav tawm kev ua haujlwm lom neeg zoo dua thiab ua haujlwm ntev dua li kisspeptin.
Txoj kev tshawb no nrhiav tau lub luag haujlwm tseem ceeb ntawm KISS1R lub voj voog peripheral hauv kev ua kom receptor. Qhov kev tshawb pom no tau lees paub los ntawm molecular dynamics simulations thiab kev tshawb fawb txog kev hloov pauv. Txoj kev tshawb no qhia txog qhov laj thawj vim li cas TAK-448 zoo dua rau KP-10 hauv kev ua kom muaj txiaj ntsig, muab lub hauv paus rau kev ua kom zoo dua ntawm KP-10 analogues. Tsis tas li ntawd, thaj tsam TM6 ntawm KISS1R nthuav tawm qhov txawv txav txawv ntawm qhov nruab nrab ntawm cov receptor piv nrog lwm cov Gq-coupled receptors. Qhov no yog qhov zoo tshaj plaws hauv kev sib txuas ntawm KISS1R rau Gq proteins. Tsis tas li ntawd, txoj kev tshawb fawb tau hais txog qhov tseem ceeb ntawm receptor TM5-ICL3-TM6 cheeb tsam hauv qab dej Gq txuas. KP-10 thiab TAK-448 txais yuav cov qauv zoo sib xws hauv lub hnab ris ligand-binding ntawm KISS1R. Lawv cov kev sib khi hom qhia tau hais tias cov seem tshwj xeeb muaj qhov cuam tshuam tseem ceeb ntawm ligand paub thiab ua kom receptor.
Cov kev tshawb fawb saum toj no nteg lub hauv paus rau kev tshawb nrhiav cov txheej txheem molecular ntawm KISS1R peptide ligand lees paub, receptor activation thiab nws coupling nrog Gq protein. Cov kev tshawb fawb ntawm cov qauv thiab kev ua haujlwm no muab kev nkag siab txog cov teeb meem hauv kev tsim kho thiab kho mob qog noj ntshav.
