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▎ Tirzepatid Strukchɔ
Sos: PubChem |
Sikyud: . Tyr-{Aib}-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Ile-{Aib}-Lyu-Asp-Lys-Ile-Ala-Gln-{diasid-C20-gamm a-Glu-(AEEA)2-Lys}-Ala-Fhe-Val-Gln-Trp-Lyu-Ile-Ala-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2 Mɔlikul Fɔmula: C 225H 348N 48O68 Molekyula Weyt: 4813 g/mol CAS Nɔmba: 2023788-19-2 PubChem CID: 163285897, ɛn di ɔda wan dɛn Sinonim dɛn: Zepbound; Mounjaro we de na di wɔl |
▎ Tirzepatid Risach
Wetin na di risach bakgrɔn fɔ Tirzepatid?
Tirzepatid na sεntetik polipεptida dכg, εn in divεlכpmεnt kכmכt frכm dip כndastandin fכ di limitεshכn dεm fכ di GLP-1 rεsεptכr agonist dεm we de naw fכ trit tayp 2 dayabεtis mεlitus εn fכ fat. pan ɔl we di GLP-1 rεsεptכr agonist dεn dכn sho se dεn de du fayn fayn wan fכ kכntrכl di blכd glukכs εn fכ lכs di wet, sayɛnsman dεm dכn fכnshכn se pan כl we dεn de aktibכt di GLP-1 rεsεptכr, dεn aktibכshכn ifekt pan di GIP rεsεptכr wik, we to wan sכm mak de limited di tεrapi ifekt fכ di dכg dεm. So, di risach ɛn divɛlɔpmɛnt tim dɔn mekɔp dɛn maynd fɔ mek wan nyu kayn drɔg we go ebul fɔ mek ɔl tu di GIPR ɛn GLP-1R aktiv wan tɛm, wit di op fɔ mek dɛn ebul fɔ kɔntrol di glukɔs na di blɔd ɛn fɔ mek dɛn ebul fɔ kɔntrol di wet we dɛn gɛt mɔ kɔmprɛhnsiv ɛn fayn fayn wan [1]. .
Insay di risach ɛn divɛlɔpmɛnt prɔses fɔ Tirzepatid, sayɛnsman dɛn dɔn du bɔku bɔku bɛsik risach ɛn klinik trial dɛn. Fɔs, insay di prɛklinik risach stej, dɛn bin dip dip wan fɔ evaluate di famakodaynamik kwaliti dɛn fɔ Tirzepatid tru animal ɛkspiriɛns, ɛn dɛn bin verify in pɔtnɛshɛl fɔ kɔntrol di glukɔs na di blɔd ɛn fɔ lɔs di wet. Di risal sho se Tirzepatid kin ridyus di blɔd glukɔs lɛvɛl bad bad wan na animal mɔdel ɛn i kin du fayn bak pan wet mɛnejɛmɛnt. Dɛn fayn fayn tin ya we dɛn fɛn bin mek wan strɔng fawndeshɔn fɔ di klinik trayal dɛn we dɛn bin du afta dat.
Afta dat, Tirzepatid bin enta di klinik trial stej, inklud di faz I, II, ɛn III trayal dɛn. Insay di faz I trayal, dɛn bin men wan fɔ ɛvaluet di sef, tolɛrabiliti, ɛn famakokinɛtik kwaliti dɛn fɔ di drɔg, ɛn di rizɔlt dɛn sho se Tirzepatid bin gɛt gud sef ɛn tolɛrabiliti. Di faz II trayal bin ɛksplɔrɔ mɔ di ɛfifikɛshɔn ɛn sef fɔ difrɛn dos dɛm fɔ Tirzepatid insay pasɛnt dɛm we gɛt tayp 2 dayabitis mɛlitus, ɛn fɔs dɛn bin disayd in ifɛktiv doz rɛnj. Di mɔs impɔtant faz III klinik trayal dɛm, lɛk di SURPASS siriɔs stɔdi dɛm, bin kɔba bɔku bɔku pipul dɛm we gɛt tayp 2 dayabitis mɛlitɔs. di risalts sho se Tirzepatid bin sכmtεm bכku pas di GLP-1 rεsεptכr agonist dεm we bin de, lεk semaglutide, fכ ridyus di blכd glukכs εn wet. Dis brekthru risal bin gi strɔng pruf sɔpɔt fɔ di makɛt aplikeshɔn fɔ Tirzepatid [1]..
Tirzepatid na polipεptida we kכmכp fכ 39 amino asid dεm, we dεn dכn mכdify wan wan amino asid dεm strכkchכral fכ impruv in stεbiliti εn efficacy. dis yכnik strכkchכral disayn de mek Tirzepatid ebul fכ intagret di ifekt dεm fכ tu inkrεtin כmon dεm, GIP εn GLP-1, insay wan mכlikul, εn aktibכt di כmon rεsεpכta dεm we de involv fכ kכntrכl di glukכs na di bכdi tru wan tu mεkanism fכ akshכn. spεshal wan, Tirzepatid kin akt pan כl tu di pankrias εn di sεntri nεv sεstem. na wan say, i de mek insulin sekreshכn εn i de mek di glukagon kכmכt, we de mek di glukכs we de na di bכdi dכn fayn fayn wan; na di ɔda say, bay we i de delay fɔ ɛmti di bɛlɛ ɛn i de mek pɔsin satisfay, i de ridyus di apɛtit ɛn it we i de it, ɛn dis de mek i ebul fɔ kɔntrol di wet. Dis tu mεkanism fכ akshכn de gi Tirzepatid yunik advantej dεm fכ trit tayp 2 dayabεtis mεlitus εn fכ fat, we de gi di sik pipul dεm wan mכr kכmprεhεnsiv tritmεnt opshכn [1]..
Wetin na di we aw Tirzepatid de wok?
Tirzepatid de lכs di glukכs na di bכdi tru mכltipכl mεkanism dεm we de wok tכgeda, lεk dis: Aktibכshכn fכ di GLP-1 rεsεpכta: Tirzepatid de biεn di GLP-1 rεsεpכta pan pankrεas β sεl dεm, we de miks di ifekt we nεchכral GLP-1 de gi. GLP-1 na כmon we dεn prodyuz na di intestin εn i implεnt fכ mεnten glukכs homכstasis 2. I kin mek insulin sεntesis, insulin sekreshכn, εn glukכs sεns, εn ridyus glukכn sekreshכn fכ mek yu satiet εn inhibit apetit 2.
dis aktibכshכn kin mek insulin sekreshכn. insulin na di men ɔmon we de mek di blɔd glukɔs go dɔŋ na di bɔdi, we kin mek di sɛl dɛn tek di glukɔs ɛn yuz am mɔ ɛn mɔ, ɛn dis kin mek di glukɔs we de na di blɔd go dɔŋ. pan di sik pipul dεm we gεt tayp 2 dayabεtis, insulin sekreshכn nכ de infεkt כ di sεl dεm in sεnsitiviti to insulin de rεdכks, we de mek di blɔd glukכs go כp. Tirzepatid de mek insulin sekreshכn bכku bay we i de aktibכt di GLP-1 rεsεpכta, we de εp fכ impruv di bכdi glukכs kכntrכl. di sem tεm, di aktibכshכn fכ di GLP-1 rεsεpכta kin inhεbit di rilis fכ glukagon bak. di glukogכn kin protεkt glycogenolysis εn gluconeogenesis insay di fast stet, we de mek di bכdi glukכs prodakshכn go כp. bay we i de inhibit di ifekt we glukagon de gi, Tirzepatid de ridyus di sכs fכ di glukכs na di bכdi, we de εp fכ kכntrכl di glukכs na di bכdi [2] (Anonymous, 2023).
aktibכshכn fכ di GIP rεsεpכta: Tirzepatid de akt pan di GIP rεsεpכta di sem tεm. afta i aktibכt, i kin εnhans insulin sεnsitiviti εn sekreshכn. di GIP risεptor de mεntal insay tisu dεm lεk pankrεas β sεl dεm. afta aktibכshכn, tru di kכndukshכn fכ di intasεlulyar signal path, insulin sekreshכn de inkrεs, εn di sεl dεm in rεspכnsiv to insulin de impruv, we de mek i de ridyus di blכd glukכs 2 mכr ifektiv wan dayabitis mεlitכs as adjunkt to it εn εksεsayz 2. Tirzepatid na sεntetik kεmikכl strכkchכ we de bays pan di GIP sikεns, we kכmכp fכ 39-amino asid pεptida. i de mek insulin sekreshכn bכku, i de ridyus di rilis fכ glukagon insay wan we we dipεnd pan glukכs, i de lכs di fast εn afta it bכdi glukכs lεvεl, i de mek yu satis, i de ridyus di wet, εn i de delay di gεstrik εmpti 2.
dis dual risεptor agonist ifekt de mek Tirzepatid mכr ifektiv fכ protεkt insulin sekreshכn εn inhibit glukagon rilis pas singl GLP-1 rεsεptכr agonist dεm [2]..
Fɔ delay fɔ ɛmti di bɛlɛ ɛn fɔ mek yu satisfay mɔ ɛn mɔ: Tirzepatid kin delay fɔ ɛmti di bɛlɛ, i kin mek di it fɔ lɔng tɛm fɔ de na di bɛlɛ, i kin mek di rit we di nyutriɛnt dɛn de tek di bɔdi slo, ɛn dis kin mek i nɔ gɛt shap inkris na di blɔd glukɔs afta yu it. insay prεklinik εn klinik stכdi dεm, di ifekt we Tirzepatid gεt pan gεstrik εmpti na kכmparabl wit di wan we GLP-1 rεsεptכr agonist dεm gεt. insay di it-induced obese mice, di digri we Tirzepatid delay di gastric empty na di sem wit di semaglutide, bכt dεn akyu inhibitory ifekt dεm ya de disappear afta 2 wiks we dεn trit am. Insay patisipan dɛn we gɛt ɛn we nɔ gɛt tayp 2 dayabitis, wan tɛm insay di wik Tirzepatid (≥5 ɛn ≥4.5mg, rispɛktvɔli) delay di gastric ɛmti afta wan doz. In hεlty patisipan dεm, dis ifekt bin atεnuet afta mכltipכl dכz כf Tirzepatid כ dulaglutide [3]. .
pan di sem tεm, i kin akt bak pan di sεntri nεv sεstem, i kin mek i satisfay, εn i kin mek i nכ want fכ it εn i nכ de it. bay we i de kכntrכl di it we dεn de it, i de εp indaykt wan fכ kכntrכl di blכd glukכs lεvεl, spεshal wan we fit fכ di fat prכblεm we bכku tεm kin kam wit di sik pipul dεm we gεt tayp 2 dayabεtis mεllitus, εn i de εp fכ impruv insulin rεsistεns εn di כvala mεtabolik stetכs [2]..
fכ impruv insulin sεnsitiviti εn lipid mεtabolism: dεn fכnshכn se tirzepatid de inkrεs di lεvεl fכ adiponectin, we na adipocytokine we riliyt to insulin sεnsitiviti. we di lεvεl fכ adiponectin inkrεs de εp fכ impruv insulin sεnsitiviti, mek di sεl dεm mכr sεnsitiv to insulin, εn dis de mek dεn tek εn yuz glukכs fayn fayn wan, we de ridyus di glukכs na di bכdi [2]..
apat frכm dat, Tirzepatid kin impruv di lipid profayl bak εn i kin gεt pכtεnshal prכtektiv ifekt pan di kכdivaskyul hεlth. dεn pruv se tirzepatid ebul fכ impruv bכdi prεshכn, rεdכks lכw-dεnsiti lipoprotein (LDL) kכlestכl εn triglisεrayd [4] .Dis de sכpכt in kכmprεhεnsiv bεnεfit dεm fכ mεnejmεnt blכd glukכs.
Risach we gɛt fɔ du wit dis
Efikכs pan wεt mεnejmεnt pan pasεnshכn dεm we fat εn tayp 2 dayabεtis mεlitus:
Bɔku klinik stɔdi dɛn dɔn kɔnfyus signifyant weit lɔs ifɛkt: Insay wan stɔdi we dɛn kɔl 'SURMOUNT-2', dis trayal na bin wan faz 3, dɛbul-blaynd, randomiz, plasɛbo-kɔntrol trial we dɛn bin du na sɛvin kɔntri dɛn. Adult (we ol ≥18 ia) wit bɔdi mas indeks (BMI) we na 27 kg/m² ɔ i pas dat ɛn wan glycated hemoglobin (HbA2c) we na 7 - 10% dɛn bin randomly asaynd fɔ gɛt wan tɛm ɛvri wik sabkyutan injɛkshɔn fɔ Tirzepatid (10mg ɔ 15mg) ɔ plasɛbo fɔ 72 wik. Di risal sho se na wik 72, di pasɛnt we di weit lɔs na di Tirzepatid 10mg ɛn 15mg grup na bin -12.8% ɛn -14.7%, rispɛktvɔli, we di wan na di plasɛbo grup na -3.2%. Di ɛstimat tritmɛnt difrɛns fɔ Tirzepatid 10mg ɛn 15mg kɔmpia wit di plesibo na bin -9.6 pasɛnt poɛnt ɛn -11.6 pasɛnt poɛnt, rispɛktvɔli, dɛn ɔl tu na bin statystikal sifyukɛnt (p 0.0001). apat frכm dat, mכr pasεnshכn dεm we dεn trit wit Tirzepatid rich di thrεshold fכ weit lכs 5% כ mכr (79 - 83% vs 32%) [5] (Garvey WT, 2023). I n di 'SURMOUNT-2' st ɔ di, di beslayn avrej wet na bin 100.7 kg, di BMI na bin 36.1 kg/m², ɛn di HbA1 na bin 8.02%. Afta 72 wiks we dɛn trit am, Tirzepatid nɔ bin jɔs ridyus di wet bad bad wan bɔt i bin ple fayn pat bak fɔ kɔntrol di glukɔs na di blɔd [5]..
Impruvmɛnt ifɛkt pan nyuropathy we gɛt fɔ du wit dayabitis:
Sɔm stɔdi dɛn dɔn sho se glukagon-layk peptide 1 rεsεptכr agonist (GLP1-RA) kin ridyus di risk fכ dimεnshכn pan di wan dεm we gεt tayp 2 dayabεtis mεlitus bay we dεn de impruv mεmכri, lan, εn כvakom di kכgnitiv impεryans. As a dual glukoz-dipεndεnt insulin polypεptida rεsεptכr agonist (GIP-RA)/GLP-1RA, dεn stכdi Tirzepatid fכ in ifekt dεm pan mak dεm fכ nyuronal grכw (CREB εn BDNF), apoptosis (BAX/Bcl2 rεshכ), difrεns (pAkt, MAP2, GAP43, εn AGBL4), εn insulin rεsistεns (GLUT1, GLUT4, GLUT3, εn SORBS1) in wan nyuroblastoma sel layn (SHSY5Y). di rizulεt fכ di fכs tεm εnfaz di rol we Tirzepatid de ple fכ aktibכt di pAkt/CREB/BDNF path εn dכwnstrim signal kaskad, εn bak in efikכs in nyuroprotεkshכn. i sho bak se Tirzepatid kin kכntrכl di ifekt dεm we riliyt to haypa glycemia εn insulin rεsistεns na di nyuronal lεvεl. fכ dat, Tirzepatid kin impruv di nyurodijεnεreshכn we de kכz fכ haypa glycemia εn i kin כvakom nyuronal insulin rεsistεns, we de gi nyu insayt fכ di impruvmεnt fכ di nyuropathy we rilayt to dayabεtis [6]. .
Risach prɔgrɛs fɔ trit tayp 2 dayabitis mɛllitus:
Sɔm stɔdi dɛn dɔn sho se Tirzepatid, as nyu kayn haypoglycemic drɔg, dɔn bi di fɔs dual GIP/GLP-1R agonist we dɛn dɔn gri fɔ trit dayabitis na Amɛrika. Dɛn dɔn kɔnfyus se i gɛt big big blɔd glukɔs-lɔring ɛn weit lɔs ifɛkt pan bɔku big-big klinik trial dɛm, ɛn pruf de fɔ se i gɛt bɔku pɔtnɛshɛl bak fɔ protɛkt di at ɛn di blɔd. apat frכm dat, di kכnsεpt fכ sεntetik pεptida dεn dכn opin plεnti posisibul dεm we dεn nכ no fכ Tirzepatid. di trayal dεm we de go bifo (NCT04166773) εn pruf dεn sho se i tan lεk se na prכmis drog na di fil dεm fכ nכn-alkohol fεt liva sik (NAFLD), rεnal εn nyuroprotεkshכn, εtk [7]..
Lɔng tɛm ifɛkt dɛm we T irzepatide gɛt pan di kadiovaskular wɛlbɔdi:
Tirzepatid kin ridyus di risk fɔ gɛt sik dɛn we de ambɔg di at ɛn di blɔd bay we i de mek pɔsin lɔs in wet. Wan stכdi bin εgzamin di impak we Tirzepatid gεt pan di fat εn kכdivaskyul sik ivent dεm pan Amεriכn big pipul dεm [8] . Di stכdi fכnshכn se pan Amεriכn big pipul dεm we fit fכ Tirzepatid tritmεnt, afta tritmεnt wit 15mg Tirzepatid, dεn εstimat se 70.6% εn 56.7% pan di big pipul dεm bin gεt weit lכs ≥15% εn ≥20%, rispεktivli, we min se di nכmba כf pipul dεm we fat bin dכn bay 58.8%. Na pipul dɛm wae nɔr gɛt dis sik na dɛn at, di ɛstimat 10 ia risk fɔ gɛt di sik dɛm na di at ɛn di blɔd kin go dɔŋ frɔm 10.1% bifo tritmɛnt to 7.7% afta tritmɛnt, we sho se di risk ridyus na 2.4% ɛn di risk ridyus na 23.6%, we min se dɛn kin ebul fɔ protɛkt 2 milyɔn di sik dɛm we kin apin insay 10 ia.
fכ kכnklud, Tirzepatid na nכvel dual agonist fכ GIP εn GLP-1 rεsεpכta dεm εn i gεt big minin fכ di tritmεnt fכ tayp 2 dayabεtis mεlitus εn fכ fat. i kin mek insulin sekreshכn mכr ifektiv, inhibit glukagon sekreshכn, prεsisli rεgulεt bכdi glukכs, rεdכks di risk fכ komplikεshכn, impruv di fכnshכn fכ pankrεas β sεl dεm, εn delay di prכgreshכn fכ dayabitis. I gɛt ɛfɛkt bak we de protɛkt di at ɛn di blɔd sistɛm. We dɛn de trit pipul dɛn we fat, i kin rili ridyus di it we dɛn de it, mek dɛn nɔ want fɔ it, i kin mek dɛn satis, ɛp di wan dɛn we fat fɔ lɛ dɛn nɔ gɛt bɔku bɔku bɔdi, ɛn i kin mek dɛn nɔ gɛt prɔblɛm dɛn we kin apin we dɛn fat pasmak. I kin mek bak di insulin rɛsistɛns ɛn lipid mɛtabolism bɛtɛ. Apat frɔm dat, i de sho se i kin ebul fɔ trit sik dɛn we gɛt fɔ du wit mɛtabolik abnɔmaliti lɛk nɔ-alkohol stiatohepatitis, slip apnia sindrom, ɛn at pwɛl, ɛn i kin mek bɔku mɛtabolik indikɛtɔ dɛn bɛtɛ wan tɛm, we kin gi mɔ kɔmprɛhnsiv tritmɛnt plan. Di we aw dɛn kin gi injɛkshɔn wan tɛm insay di wik kin izi fɔ yuz ɛn i kin mek di sikman dɛn fala di tritmɛnt we dɛn de gi dɛn. We dɛn kɔntrol di glukɔs ɛn wet na di blɔd fayn fayn wan ɛn ridyus di risk fɔ gɛt prɔblɛm dɛn, dɛn kin rili impɔtant, dɛn kin ebul fɔ du tin dɛn ɛvride ɛn di kwaliti fɔ liv, dɛn kin gɛt mɔ kɔnfidɛns fɔ kɔntrol di sik, dɛn kin pul dɛn maynd prɔblɛm, ɛn dɛn kin ebul fɔ adap to ɔda pipul dɛn.
Bɔt di pɔsin we rayt di buk
Di tin dɛn we wi dɔn tɔk bɔt ɔp, na ɔl di tin dɛn we Cocer Peptides dɔn du risach, ɛdit ɛn kɔmpilayt.
Sayɛns Jɔnal Author
Dɔktɔ Wiliam T. Gavi na wan big masta sabi bukman ɛn risachman we gɛt fɔ du wit bɔku bɔku big big institiushɔn dɛn, lɛk di Yunivasiti ɔf Alabama na Bɛmingham, Aston Yunivasiti, ɛn di Bɛmingham Veterans Afɛj Mɛdikal Sɛnta. In akademik bakgrɔn ɛn in wok ɛkspiriɛns span bɔku difrɛn disiplin dɛn insay di mɛdikal ɛn sayɛns fild dɛn. Dɔktɔ Garvey dɔn mek bɔku kɔntribyushɔn to di fild dɛm fɔ ɛndokrinɔlɔji ɛn mɛtabolism, nyutrishɔn ɛn itɛttiks, bayɔkemistri ɛn mɔlikul bayoloji, ɛn bak jenɛral ɛn intanɛnt mɛrɛsin, wit patikyula fɔs pan di kadiovaskular sistɛm ɛn kadiɔlɔji. Bɔku pipul dɛn dɔn no ɛn ɔnɔ in wok, mɔ we dɛn kɔl am Highly Cited Researcher in di Cross-Field kategori fɔ ɔl tu di 2023 ɛn 2024, we sho di big impak ɛn inflɛns we in risach gɛt pan di brayt sayɛns kɔmyuniti.
Dכkta Garvey in risach intres εn εkspεriεns de εksεnd to difrεn aspek dεm fכ mεtabolik sik dεm εn dεn mεnejmεnt. I dɔn de wok tranga wan fɔ stɔdi bɔt dayabitis, fɔ fat, ɛn di prɔblɛm dɛn we gɛt fɔ du wit dɛn, ɛn i dɔn aim fɔ fɛn nyu tritmɛnt strateji ɛn fɔ mek di pɔsin gɛt bɛtɛ tin fɔ du. In wok inkɔmpas besik sayɛns risach, klinik trial, ɛn transleshɔnal stɔdi, we de briŋ di gap bitwin di tin dɛn we dɛn dɔn fɛn na lɛbɔretri ɛn di rial wɔl mɛdikal aplikeshɔn dɛn. Tru in bɔku risach, Dɔkta Garvey dɔn kɔntribyut fɔ ɔndastand mɔ bɔt di ɔndalayn mɛkanism dɛm fɔ mɛtabolik dizayd ɛn i dɔn ɛp fɔ shep klinik gaydlayn ɛn tritmɛnt protɔkɔl dɛm na di fild fɔ ɛndokrinɔlɔji ɛn mɛtabolism. Dɛn rayt Dɔktɔ Wiliam T. Gavi insay di rɛfrɛns fɔ saytayshɔn [5]..
