Shaanxi Bloom Tech Co., Ltd. yog ib qho ntawm cov neeg tsim khoom lag luam thiab cov chaw muag khoom ntawm Ligandrol (LGD-4033) hauv Suav teb. Txais tos rau kev lag luam wholesale ntau qhov zoo zoo lighadrol (LGD-4033) Kev muag khoom ntawm no los ntawm peb lub hoobkas. Cov kev pabcuam zoo thiab tus nqi tsim nyog muaj.
Ligandrol (LGD-4033)Yog ib qho kev xaiv Androgen Receptor Modiulator (sarm), tsuas yog siv rau kev kho cov leeg atrophy thiab osteoporosis. Nws xaiv cov roj ntsha and secogen hauv cov leeg pob txha, txhawb kev loj hlob ntawm cov nqaij cuam tshuam rau cov nqaij mos xws li cov kua xoo. Cov kev tshawb fawb preclinical tau qhia tias LGD- 4033 tuaj yeem ua rau lub cev nqaij ntshiv mob, thiab muaj siab dua ntawm lub neej nrog ib nrab-lub neej ntawm kwv yees li 24-36 teev.
Txawm hais tias tseem tsis tau pom zoo los ntawm FDA, LGD {{1} Tau tsim txom los ntawm cov neeg ncaws pob thiab tus neeg nyiam ua haujlwm ntawm nws lub tsev. Cov kev phiv los yog muaj me me testosterone supress, mob taub hau thiab qaug zog. Lub ntev - kev nyab xeeb yog tsis paub. Lub ntiaj teb anti-doping lub koom haum (Wada) txwv tsis pub siv. Cov kev tshawb fawb ntxiv yog xav tau los xyuas nws lub peev xwm kho mob thiab kev pheej hmoo. Tam sim no, nws tseem nyob hauv cov theem kev sim thiab tsis raug muag raws li cov tshuaj.
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Ligandrol (LGD-4033) HMOOV COA
Ligandrol (Tshuaj Lom Zem LGD-}}}}}}}}} tus lej 1165910-22-4) yog hom tshiab ntawm qhov ncauj tsis yog steroidal qhov ncauj thiab sterm). Nws cov tshuaj muaj sia yog 4 - [(2R) -2 - [(1-Hydrluoromethyl) polecular hnyav ntawm 338.25 g / mol. Nws cov tshuaj chemical tuaj yeem txheeb xyuas los ntawm cov hauv qab no:
Cov Khoom Siv Lub Cev
Cov tsos thiab daim ntawv:Dawb rau lub teeb beige crystalline khoom, hygroscopic, yuav tsum tau khaws cia rau hauv ib puag ncig qhuav.
Melting taw tes thiab boiling taw tes:Melting point yog 108-111 degree, kwv yees lub boiling point yog 439.9 ± 45.0℃taw tes taw qhia cov zog sib xyaw muaj zog).
Ntawj ntom thiab solubility:Kev kwv yees ntom yog 1.45 ± 0.1 g / cmle, solle soluble hauv acetone, chloroform (hauv cov kev mob cua sov), thiab methanol. Solubility yog cuam tshuam ntau dhau los ntawm qhov kub thiab kub polarity.
Acidity coefficient (PKA):Kwv yees tus nqi yog 12.06 ± 0.20, qhia tau tias nws muaj ua ib qho chaw tos phatiological thiab receptor binding muaj peev xwm.
Cov qauv tshuaj lom neeg thiab kev ua haujlwm sib raug zoo
Cov pob txha tseem ceeb:Muaj los ntawm pyrrolidine nplhaib thiab benzoyl pab pawg. A (1R) -2,2,2-trifluoro-1-hydroxyethyl sab saw yog txuas rau ntawm 2 txoj haujlwm ntawm tus qauv fenorinated molecular.
Lub luag haujlwm ntawm kev hloov kho fluorination:
Enhenance lipid solubility, txhim kho cov ntshav - bior stration nkag peev muaj peev xwm (txawm hais tias tsis muaj kev faib tawm thiab metabolism).
Txhab cov khoom siv rov qab los ntawm cov nyhuv hluav taws xob, Enhance affinity rau Androgen receptor (AR) (KI ≈ 1 nm).
Chairal Center:The molecule contains two chiral carbons (1R and 2R configurations), stereoselective synthesis ensures high selectivity for AR binding, avoiding non-target tissue (such as prostate, liver) non-specific interactions.
Cov yam ntxwv ntawm cov chaw ua ke
Qhov ncauj Bioavailability:Raws li qhov tsis - steroidal sarm, {2} Tau ua tiav qhov kev hloov kho kom haum, zam kev mob siab rau cov tshuaj steroids.
Ib nrab - lub neej thiab tsub zuj zuj:Tshem tawm ib nrab - lub neej yog 24 - 36 teev, txhawb nqa ib zaug-txhua hnub tswj hwm; Pharmaconininet qhia pom cov kab mob sib txuam, thiab ntshav tshuaj ntau yog ruaj khov tom qab kev tswj hwm.
Metabolic stability:Cov khoom ua pov thawj zoo metabolic ruaj khov nyob rau hauv cov tsiaj tsiaj, tsuas yog metabolized los ntawm daim siab lom zem, tsuas yog rau siab -}}}}}} kev siv sijhawm).
Tshuaj lom neeg sab nrauv thiab kev cia khoom
Thermal Stability:Melting taw qhia cov ntaub ntawv qhia ruaj khov ntawm ib txwm kub, tab sis zam dhau high - qhov chaw ib puag ncig kom tiv thaiv kev lom zem.
Lub teeb ruaj khov:Tsis muaj ntaub ntawv ntawm phototoxicity tau tshaj tawm, tab sis fluorinated muaj ntxhiab tsw feem ntau yuav tsum tau kev tiv thaiv los tiv thaiv cov photooxidation kev txwv.
Yuav tsum yuav tsum tau cia:Pom zoo rau khov ntawm- 20℃yuav tsum tau {}}}}} lub sij hawm ruaj khov; Thaum lub sij hawm thauj mus los, siv Ultra - Qhov tsawg ntawm cov dej khov hauv dej khov kom muaj qhov tsawg-qhov kub.
Kev Nyab Xeeb thiab Kev Lom Zem
Toxicity toxicity: Kev tshawb fawb preclinical qhia tau tias nyob rau hauv cov tsiaj primate cov qauv, tsis muaj kev tiv thaiv hnyav
Ntev - cov kev cuam tshuam: Raws li kev tshawb fawb sib txuas, ntev -} Cov txiv neej kev nyab xeeb, tab sis cov txiv neej Testosterone tau rov qab los ntawm kev sib tw tom qab 56 hnub ntawm kev sib txuas.
Kob Txom Nyem Tswj:Siab - purity (ntau dua los yog sib npaug ntawm 97%) tuaj yeem txo qhov kev pheej hmoo tsis paub, thiab kev tswj hwm zoo xws li HPLC thiab NMR yuav tsum muaj tshuaj tsis sib xws.
Kev Tshawb Fawb Cov Lus Qhia: Los ntawm cov kev cov nyom ntawm Androgen Kev Kho Mob rau lub hnub yug ntawm sarms
Nyob rau hauv lub xyoo pua 20th, ib txwm muaj kev kho mob (xws li kev ntsuas lub twj siab (xws li cov tshuaj tua kab mob cancia, {} ‖ epleoporosis):
Hloov Chaw Tsim Tshuaj Pauv:Cov kev mob anabolic ntawm cov testosterone ntawm cov leeg thiab pob txha tsis txawv ntawm cov nqaij mos xws li prostate hyperplasia, ntxau, thiab gynecomastia.
Pharcacotaus txwv txwv:Testosterone yuav tsum tau muab tswj los ntawm kev txhaj tshuaj, thiab nws qhov ncauj bioavailability yog tsawg. Ntxiv mus, cov kua zaub ntawm qhov ncauj hloov kho los ntawm 17 - alkylation (xws li methyltestosterone) muaj hepatotoxicity.
Kev kho qhov rai yog nqaim:Cov koob tshuaj ntawm anabolic cov txiaj ntsig yog koob - Nyob ntawm Androgenic phiv, txwv nws cov neeg mob lossis poj niam.
Xyoo 1998, lub tswv yim ntawm xaiv Androgen Revenor Modulators (sarms) tau npaj siab, nrog lub hom phiaj tseem ceeb tau ua tiav los ntawm cov qauv molecular:
Cov nqaij so ntswg - Cov txiaj ntsig tshwj xeeb: nws tau tawm ib qho kev ua haujlwm Anabolic hauv cov leeg thiab cov pob txha, thaum tsis txhob muaj kev ua si nrog cov nqaij mos.
Qhov ncauj Bioavailability: nws tuaj yeem nqus tau yam tsis muaj kev xav tau rau daim siab kev hloov kho.
Kev ruaj ntseg kev ua kom muaj kev ruaj ntseg: nws txo cov inhibition) {pituitary axis (HPTA) thiab lowers plawv plawv thiab lowabololular thiab letabolic kev pheej hmoo.
Kev tshawb nrhiav pom thiab kev txhim kho thaum ntxov: Ligand Pharmaceuticals 'breakfrough (2007-2010)
Molecular Tsim
Ligandrol (LGD-4033)Tau synthesized los ntawm American Biopharraceutical tuam txhab Ligand Photracuticals hauv 2007. Nws cov qauv tshuaj lom neeg yog raws li cov pyrrolidine thiab fluorinated cov pab pawg muaj ntxhiab. Kev xaiv tau ua tiav los ntawm cov qauv hauv qab no:
Fluorination hloov kho:Lub Trifluorethyl thiab hydroxyethyl sab saw ntawm lub nplhaib Benzene, txhawb nqa kev lees paub tshwj xeeb ntawm cov hnab tshos recing.
Stereoconfiguration Xauv:Ob chairal Chaw (1R, kom paub meej tias lub kaum sab xis, tsis txhob muaj kev cuam tshuam nrog cov tshuaj lom neeg ntawm cov ntaub so ntswg prostate.
Cov Kev Kawm Ua Ntej (2008-2010)
Cov Qauv Cov Npaum Cas:In castrated rats, after administration of LGD-4033 at a dose of 0.1-3 mg/kg for 14 days, the mass of the quadriceps femoris increased by 20%-35%, while the volume of the prostate showed no significant change, and the ratio of anabolic/androgenic selectivity was >500: 1 (Testubterone yog 2: 1).
Primate qauv:Hauv Rhesus liab, tswj hwm LGD-4033 (0.6-15 mg / kg / hnub) ua rau lub siab ntshiv mob lossis prostate hyperplasia. Qhov 75 mg / kg pab pawg tau txiav tawm vim muaj kuab lom.
Osteoporosis qauv:Nyob rau hauv ovariectomized nas, ntawm lub ntsiab lus ntawm LGD-4033 (1 mg / Kg / hnub) ua rau muaj kev nce qib siab txog li 8.3%
Cov ntaub ntawv no qhia tias LGD-4033 tau ua tiav lub hom phiaj "kho cov txiaj ntsig ntawm Testosterone tsis muaj nws cov kev mob tshwm sim" hauv cov qauv sib txuam.
Kho Mob Txoj Kev Kho Mob: Viking Kho Cov 'Kev Kawm (2010-2020)
Xyoo 2010, Ligand Photouticals tso cai LGD-4033 mus rau Veste muaj npe hu ua VK5211 thiab coj cov hmoov txhuas tom qab kuaj mob:
Theem Kuv Tau Kev Hais (2015-2017)
76 Cov txiv neej noj qab haus huv cov neeg kawm tau txais koob tshuaj uas tau txais los ntawm 0.1 txog 1.0 mg / hnub. Tom qab 21 hnub:
Ntse lub cev loj nce los ntawm 1.21 kg (1 MG pawg), thiab ntaiv nce toj muaj peev xwm los ntawm 15.2%.
Qib Testosterone poob qis los ntawm 35% -50%, tab sis cov zoo nkauj tom qab 56 hnub ntawm kev txuas.
Tsis tau tshaj tawm cov xwm txheej hnyav tau tshaj tawm. Ntshav lipid thiab daim siab enzyme txhais tau compliced luv luv thiab rov qab mus rau qhov qub.
Ntu IITh (2018-2020)
Lub VK5211-201 kawm (NCT02946278) Rau cov neeg mob nrog pob ntseg pob ntseg pom:
Tom qab 12 lub lis piam ntawm kev kho, femoral caj dab pob txha ua kom nce ntxiv los ntawm 1.8%, thiab taug kev nrawm dua los ntawm 0.12 m / s.
Cov leeg ua kom zoo tsis tu ncua kom txog 24 lub lis piam tom qab kev kho mob thaum kawg, thiab tsis muaj tus mob prostjasia lossis tus txiv neej lub mis tau pom.
Kev sib cav sib ceg thiab cov kev cai uas muaj kev sib tw (2017-tam sim no)
Anti - Cov teeb meem doping
Nyob rau hauv 2018, lub ntiaj teb anti - chaw haujlwm koom haum (Wada) muaj cov npe raug txwv, thiab nws cov metabliv tuaj yeem raug kuaj pom hauv cov zis rau cov zis mus txog 40 hnub.
Nyob rau hauv 2019, Australian Shaiyna Jack tau raug ncua rau 4 xyoos vim yog kev kuaj tshuaj zoo, dhau los ua thawj rooj plaub.
Kev ua lag luam kev ua lag luam
Synthetic LGD-4033 tsim los ntawm cov chaw muag tshuaj yog feem ntau tov nrog anabolic steroids xws li methyltesterone, ua rau muaj kev cuam tshuam loj heev.
Kev kuaj mob qhia tias 63% ntawm "Tshawb Fawb Tshuaj" tsis phim cov ntawv sau rau hauv cov ntsiab lus uas hnyav tau mus txog 28%.
Raws cai
TEB CHAWS USA: Kev siv tshuaj tsis pab, kev siv tus kheej yuav ntsib tus nqi $ 1,000 tus nqi nplua nuj, faib ua txhaum cai.
Tuam Tshoj: Tswj nyob rau hauv "anti {{{0} kev siv doping", kev siv tsis raug cai tuaj yeem muaj txog li 15 hnub ntawm kev raug nplua thiab muaj kev sib raug zoo txog 30,000 leej.
Cov Lus Qhia Yav Tom Ntej: Los ntawm kev kho mob rau cov tshuaj tus kheej
Kev Loj Hlob Tshiab
LGD {{2- 4033-D3 (D3 (DUALATED VERSION) yog kev sim siab ntev txog ib nrab-lub neej mus rau 72 teev thiab txo cov nqi hluav taws xob.
Kev Kho Mob Kev Kho Mob Tshawb Fawb
Qhov II theem kev sib txuas nrog cov actriib inhibitors rau kev kho mob txha caj qaum Atrophy (SMA) tau taug kev 6-feeb taug kev deb ntawm 47 meters.
Daim ntawv thov tshuaj rau tus kheej tshuaj
Kev tsom xam ntawm kev ua gene polymorphisms tuaj yeem kwv yees cov lus teb rau ib qhoLigandrol (LGD-4033), thiab cov tib neeg nrog CAG rov ua lej <22 muaj kev txhim kho 40% ntawm cov leeg kev loj hlob.
Cov tshuaj tiv thaiv tsis zoo
Ligandrol (LGD-4033) yog ib qho kev xaiv AndreCen Receny thiab Osteoporicitions nyob rau xyoo 2007. Nws tuaj yeem tsim cov ntaub so ntswg thiab cov pob txha sib tw Zam kev phiv tawm ntawm lwm cov ntaub so ntswg xws li daim prostate thiab mob siab. Txawm li cas los xij, nrog rau kev siv ntawm LGD-4033 hauv kev ua kis las thiab kis las, nws cov kev tsis zoo tau tau txais maj mam tau txais kev mloog.
Endocrine cuam tshuam
Testosterone inhibition
LGD-4033 muaj ib qho tseem ceeb inhitosity nyhuv rau ntawm hypothalic pituitary ntxaij cov kab keyuam nti Nyob rau hauv theem kuv kuaj mob kev sim siab, cov txiv neej noj qab haus huv uas coj mus rau qib 133 Tom qab 56 hnub ntawm kev txuas ntxiv, cov phiaj xwm testosterone tau rov qab los rau hauv paus. Txawm li cas los xij, hauv kev siv tiag tiag, cov tshuaj siv tau ntau dua (5-10 milligrams / hnub), uas yuav ua rau muaj zog qis dua, qaug zog, tsis muaj mob rau cov tsos mob.
Kom nce qib tshuaj estrogen
Thaum LGD-4033 khi rau androgen receptors, nws pheej yig qhov kev txiav txim ntawm lub cev testosterone, ua kom yooj yim rau testosterone kom hloov mus rau estrogen. Qhov no yuav ua rau cov tshuaj estrogen cuam tshuam, xws li tsam plab thiab txiv neej lub mis. Txawm hais tias LGD-4033 nws tus kheej tsis ncaj qha txhawb cov khoom siv tshuaj estrogen, qhov kev nce qib qis hauv estrogen qib tshwm sim los ntawm nws tseem xav tau ceev faj.
Txo kev sib deev puas poob qis ntawm cov pob zeb ua haujlwm (shbg)
LGD-4033 tuaj yeem qis dua ShbG qib, tso cai rau testosterone pub dawb kom ua. Txawm li cas los xij, cov nyhuv no tuaj yeem ua rau muaj kev cuam tshuam endocrine endocrine thiab cuam tshuam cov tshuaj tiv thaiv txhua lub zog hauv cov ntsiab lus ntawm testosterone.
Cim npe nrov: Nigandrol (LGD-4033), Cov chaw tsim khoom, chaw tsim khoom, chaw tsim khoom, lag luam, yuav khoom, nqe, loj, rau muag