5-Amino-1MQ 10mg

▎ 5-Amino-1MQ Imiterere

▎ 5-Amino-1MQ Ubushakashatsi

Ni ubuhe bushakashatsi bwakozwe kuri 5-Amino-1MQ?

Hamwe n’ubwiyongere bukabije bw’imibare y’indwara ziterwa na metabolike nk’umubyibuho ukabije na diyabete, kumenya intego n’ibiyobyabwenge bishobora kugenga neza metabolisme y’ingufu no guteza imbere indwara ziterwa na metabolike byabaye intego y’ubushakashatsi. Nikotinamide N-methyltransferase (NNMT), enzyme yingenzi ya metabolike, igira uruhare runini mumbaraga homeostasis. Gukabya gukabije kuganisha ku bibazo nko kwegeranya ibinure no kurwanya insuline, bigatuma amabwiriza ya NNMT ashobora kuba intego yo kuvura indwara zifitanye isano.

Kuruhande rwinyuma, 5-Amino-1MQ yagaragaye nkibikoresho byihariye bya NNMT. Muguhagarika ibikorwa bya NNMT, bigabanya methylation ya nicotinamide idasanzwe, igarura urwego rwimitsi ya NAD + kandi igahindura inzira zerekana ibimenyetso bifitanye isano, bityo igahindura metabolisme ya lipide kandi ikongerera insuline. 5-Amino-1-methylquinolinium yagaragaye nkintego yingenzi yubushakashatsi bugamije gushakisha ingamba zo kuvura udushya zo kurwanya indwara ziterwa na metabolike, bituma ubushakashatsi bwibanze ku mikorere yabwo.

Ni izihe ngaruka 5-Amino-1-methylquinolinium igira kuri metabolism ya adipocyte?

Ingaruka kuri Adipogenezi

Kubuza Adipogenezi: Adipogenezi bivuga inzira aho preadipocytes itandukanya adipocytes ikuze kandi ikusanya lipide mugihe cyo gukura kwa adipocyte. Ubushakashatsi bwerekana ko methylquinolinium scafolds ifite insimburangingo ya amine yerekana uburyo bworoshye bwo gutwara ibintu byoroheje kandi bikora, mu gihe ibigereranyo byabo byerekana ibikorwa byo guhagarika cyane kurwanya nikotinamide N-methyltransferase (NNMT) ^[1] . Inhibitori ya NNMT irwanya adipogenez muri adipocytes, biganisha kuri hypothesis ivuga ko 5-Amino-1-methylquinolinium, niba ifite ibikorwa nkibi byo guhagarika NNMT, birashoboka cyane kugabanya adipogenezi mukubuza NNMT. Kurugero, mubushakashatsi bwa adipocyte bwumuco, inhibitori ya NNMT igabanya urwego rwimitsi 1-methylnicotinamide (1-MNA), kongera nicotinamide adenine dinucleotide (NAD⁺) na S- (5'-adenosyl) -L-methionine (SAM), kandi ikabuza adipogenezi muma selile ^..

Guhindura imvugo ya adipogenezi ifitanye isano na gene: Adipogenezi igengwa nuruhererekane rwibintu byandikirwa hamwe na gen, nka peroxisome prolifator-ikora reseptor-gamma (PPAR-γ) na CCAAT / kongera imbaraga-zihuza poroteyine (C / EBP). Ibikomoka kuri Methylquinoline byanze bikunze bigira ingaruka kuri lipogenezi muguhindura imvugo ya genes zingenzi.

Igicapo 1 Guhitamo hamwe na membrane-byemerwa na molekile ntoya ya nikotinamide N-methyltransferase ihindura ibinure byinshi byamavuta biterwa numubyibuho ukabije nimbeba.

Inkomoko: ScienceDirect ^[1]

Ingaruka kuri Lipid Metabolism

Kugena poroteyine zigira uruhare muri synthesis ya lipide no gutesha agaciro: Lipid metabolism ikubiyemo inzira nka synthesis ya lipide, kubika, no kwangirika. Mu bushakashatsi bwakozwe ku ndwara zifata umwijima ziterwa na metabolike (MAFLD), Donglingcao ihindura ibikorwa bya peroxisome prolifator-ikora reseptor -α (PPAR-α), sterol igenga ibintu-ihuza poroteyine-1c (SREBP-1c), synthase ya aside irike (FAS), na acetyl-CoA carboxylase (ACC). 5-Amino-1-methylquinolinium irashobora guhindura metabolisme ya lipide muri adipocytes hakoreshejwe uburyo busa, nko kugenzura imvugo ya poroteyine zingenzi zigira uruhare muri synthesis ya lipide no kwangirika. Kurugero, niba 5-Amino-1-methylquinolinium ishobora kugenzura imvugo ya PPAR-α, irashobora guteza okiside ya aside irike kandi ikagabanya kwirundanya kwa lipide muri adipocytes. Ibinyuranye, niba bigira ingaruka kumvugo ya SREBP-1c, FAS, nibindi, birashobora guhindura imikorere ya synthesis ya fatty acide.

Guhindura urwego rwimikorere ya metabolite kugirango bigire ingaruka kuri metabolisme ya lipide: Urwego rwa metabolite rwimbere rufite uruhare runini mugutegeka metabolism. Nkuko byavuzwe haruguru, inhibitori ya NNMT irashobora guhindura urwego rwimitsi ya metabolite nka 1-MNA, NAD⁺, na SAM, bityo bikagira ingaruka kuri metabolism adipocyte ^[1] . Niba 5-Amino-1-methylquinolinium itanga ingaruka nkizo murwego rwa metabolite, byagenga mu buryo butaziguye metabolisme ya lipide. Nka coenzyme ikomeye yingirakamaro igira uruhare munzira nyinshi zo guhinduranya, ihinduka murwego rwa NAD⁺ rishobora kugira ingaruka kumikorere ya lipide metabolism nka okiside ya aside irike hamwe na acide ya tricarboxylic.

Ingaruka kuri Metabolism Ingufu

Ingaruka ku gikorwa cya Mitochondrial: Ingufu za metabolisme muri adipocytes zifitanye isano rya bugufi n'imikorere ya mito-iyambere. Ubushakashatsi bwerekana ko muri vitro yigana imiterere irambuye irambuye, ibikorwa bya mitochondial muri adipocytes byiyongera, bigatera lipogenezi no kwihutisha metabolisme ya selile ^[2] . Methylquinolinium ivanze irashobora guhindura ibikorwa bya mitochondial muguhindura inzira ya metabolike ijyanye na metabolike cyangwa imvugo ya protein. Niba 5-Amino-1-methylquinolinium ibuza poroteyine zimwe na zimwe za mito-iyambere cyangwa uburyo bwo guhinduranya ibintu, irashobora kugabanya ibikorwa bya mito-iyambere kandi bikagabanya ingufu zikoreshwa muri adipocytes. Ibinyuranye, irashobora guteza imbere imbaraga za metabolism. Kurugero, muguhindura ibikorwa byurwego rwubuhumekero rwa mitochondrial, bishobora kugenga umusaruro wa ATP, bityo bikagira ingaruka kumiterere yingufu no guhindagurika kwa adipocytes.

Kugenga ingufu za adipocyte: Adipocytes ntabwo ibika ingufu gusa ahubwo inagira uruhare mukugenzura ingufu zingana. Ingaruka za 5-Amino-1-methylquinolinium kuri metabolism ya adipocyte irashobora kugaragara muburyo bwo kugenzura ingufu. Niba ibuza lipogenezi kandi igatera lipolysis, irashobora kugabanya kubika ingufu no kongera ingufu muri adipocytes. Ku rundi ruhande, niba iteza lipogenezi kandi ikabuza lipolysis, irashobora gutuma habaho kwirundanya gukabije muri adipocytes, bigahungabanya ingufu zingana - ikintu gikomeye mu iterambere ry’umubyibuho ukabije hamwe n’indwara ziterwa na metabolike.

Ingaruka kumikorere ya Adipocyte Endocrine

Ingaruka zo gusohora kwa adipokine: Nka ngingo ya endocrine, adipocytes isohora adipokine nyinshi nka leptine na adiponectine, bigira uruhare runini mu kugenzura imikorere ya metabolisme ^[3] . Ibiyobyabwenge cyangwa ibintu bimwe na bimwe birashobora kugira ingaruka kuri adipocyte gusohora kwa adipokine. Nubwo nta bimenyetso bifatika bihari byerekeranye n'ingaruka za 5-Amino-1-methylquinolinium ku musemburo wa adipokine, ingaruka rusange muri metabolism ya adipocyte yerekana ko hashobora kubaho uburyo butaziguye bwo gusohora kwa adipokine. Niba 5-Amino-1-methylquinolinium ihinduye ingufu za adipocyte cyangwa metabolisme ya lipide, irashobora gutanga ibitekerezo-bigenga ururenda rwa leptine. Nka molekile yerekana ububiko bwibinure, impinduka mumyanya ya leptine igira ingaruka kubyo kurya no guhinduranya imbaraga.

Gutera Indwara ya Cytokine Yangiza: Imiterere yumubiri wa adipose ifitanye isano rya bugufi na metabolism ya adipocyte. Adipocytes irashobora gusohora cytokine zitandukanye zitera umuriro, nka interleukin-1β (IL-1β), interleukin-6 (IL-6), hamwe nikibyimba cya niyose-α (TNF-α) (Michalczyk K). Mu bihugu bifite umubyibuho ukabije, kwiyongera kwa tipusi ya adipose biganisha ku gusohora kwinshi kwibi bintu bitera umuriro, nyuma bikagira ingaruka kuri metabolisme ya sisitemu no kumva insuline. 5-Amino-1-methylquinolinium, niba ishoboye kugenzura metabolisme ya adipocyte, irashobora guhindura ururenda rwa cytokine, bityo bikagira ingaruka ku mikorobe yangiza ibidukikije ya adipose kandi bikagira ingaruka ku mibabaro ziterwa no kubyibuha. Ubushobozi bwayo bwo guhagarika ururenda rwa cytokine rushobora gufasha kugabanya insuline irwanya no kunoza imiterere ya metabolike.

Ibyerekeye Umwanditsi

Ibikoresho byavuzwe haruguru byose byakorewe ubushakashatsi, byahinduwe kandi byakozwe na Cocer Peptides.

Umwanditsi w'ikinyamakuru

Harshini Neelakantan ni umuhanga mu bya farumasi akaba n’umuyobozi w’ubushakashatsi ufite uburambe bunini mu iterambere ry’ibiyobyabwenge mbere y’indwara ziterwa na metabolike, neurologiya, na musculoskeletal. Kugeza ubu akora nk'umuyobozi mukuru w’ubushakashatsi n’iterambere muri Ridgeline Therapeutics, yibanda ku buhinduzi bw’imiti mito mito ivura kuva hit-to-lead yemerewe gukoreshwa kwa muganga. Ubuhanga bwe bukora muri farumasi ya vivo, kwerekana imiterere y’indwara, no guhindagura ibiyobyabwenge, kandi mbere yakoraga mu ishami ry’ubuvuzi rya kaminuza ya Texas.Harshini Neelakantan yanditse ku rutonde rwavuzwe [1].

Imirongo ijyanye

[1] Neelakantan H, Vance V, Wetzel MD, n'abandi. Guhitamo hamwe na membrane-byemerwa na molekile ntoya ya nikotinamide N-methyltransferase ihindura indyo yuzuye ibinure biterwa n'umubyibuho ukabije mu mbeba. Ibinyabuzima bya farumasi y’ibinyabuzima 2018; 147: 141-152.DOI: 10.1016 / j.bcp.2017.11.007.

[2] Mor-Yossef ML, Kislev N, Lustig M, Pomeraniec L, Benayahu D. Ingaruka zo gukangura ibinyabuzima kuri metabolism ya adipocyte. Ikinyamakuru cya Cellular Physiology 2020; 235(11): 8702-8713.DOI: 10.1002 / jcp.29714.

] Gusuzuma 2021; 11(3) .DOI: 10.3390 / kwisuzumisha11030494.

INGINGO ZOSE N'AMAKURU Y’IBICURUZWA BITANZWE KURI URU RUBUGA BISANZWE KUBONA AMAKURU N'INTEGO Z'UBUREZI.  

Ibicuruzwa byatanzwe kururu rubuga bigenewe gusa mubushakashatsi bwa vitro. Mu bushakashatsi bwa vitro (Ikilatini: * mu kirahure *, bisobanura mu bikoresho by'ibirahure) bikorwa hanze y'umubiri w'umuntu. Ibicuruzwa ntabwo ari imiti, ntabwo byemejwe n’ikigo cy’Amerika gishinzwe ibiryo n’ibiyobyabwenge (FDA), kandi ntigomba gukoreshwa mu gukumira, kuvura, cyangwa gukiza indwara iyo ari yo yose y’ubuvuzi, indwara, cyangwa indwara. Birabujijwe rwose n'amategeko kwinjiza ibyo bicuruzwa mumubiri wabantu cyangwa inyamaswa muburyo ubwo aribwo bwose.