Acp-105 Hmoovyog qhov sib txuas uas muaj nyob hauv daim ntawv hmoov, thiab nws cov ntxhais sib xyaw yog ACP-105. Acp-105 belongs rau qeb ntawm xaiv Androgen tus receptor modulators (sarm), nrog cov kev ua ub no muaj txiaj ntsig, thiab muaj cov ntawv thov muaj txiaj ntsig zoo hauv kev tshawb fawb. Acp-105 muaj kev ua si zoo hauv cov kuab tshuaj yeeb yaj kiab (xws li DMOPS), uas muab kev npaj rau nws thiab siv hauv kev sim. Nyob rau hauv cov kev cia uas tsim nyog (xws li -20 degree), cov hmoov no tuaj yeem tswj kev ruaj khov rau lub sijhawm ntev, nrog kev coj dawb huv tau ncav cuag kom siab li 99.53%.
Qhov no cov hmoov ntshiab yuav tsum tau muab cia rau hauv qhov chaw qhuav thiab txias, zam kev ua tshav ntuj thiab qhov kub. Feem ntau hais lus, cov pom zoo cia kom sov yog -20 degree, thiab lub txee lub neej tuaj yeem ncav cuag 2 mus rau 3 xyoos. Thaum lub sijhawm cia, lub thawv yuav tsum tau muab khi kom tiv thaiv kom txhob muaj cov hmoov los ntawm kev nqus dej los yog tsis zoo.
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Acp-105 Hmoov Coob
Acp-105 HmoovYog ib qho kev xaiv Androgen Receptor Modulator (sarm), thiab nws cov tshuaj ruaj khov yog cuam tshuam los ntawm ntau yam. Cov hauv qab no yog kev tsom xam ntawm nws cov kev ruaj ntseg los ntawm kev sib tham xws li cov xwm txheej cia, tshuaj lom neeg, thiab ib puag ncig cov khoom.
Tus cawv ntawm kev cia khoom rau kev ruaj ntseg
Tswj Qhov Kub
Qhov ruaj khov ntawm cov hmoov no yog ze rau qhov chaw cia khoom kub.Qhov feem ntau pom zoo kom muab nws tso rau hauv tub yees huab cua ntawm 2 {} 8 degree. Qee tus neeg xa khoom qhia tias cov hmoov nplej tau tuaj yeem khaws cia rau 3 xyoos ntawm -20 degree. Kev kub-taws kub ib puag ncig yuav ua kom nws qhov kev mob siab, yog li ntawd yog qhov kub siab dua.
Cia kom deb ntawm lub teeb thiab qhuav
Lub teeb thiab cov av noo yog qhov tseem ceeb ua rau kev txiav txim siab ntawm acp - 105. Cov khoom yuav tsum tau muab ntim rau hauv ib qho qhuav thiab lub teeb- ntawv pov thawj los tiv thaiv kev nqus dej noo thiab yees duab}}}}}}}} oxidation. Qee tus neeg xa khoom taw qhia txog kev khaws cia ntawm "ua kom qhuav thiab teeb pom kev zoo" los tswj kev ncaj ncees ntawm lawv cov qauv tshuaj.
Faib thiab Khw
Yog tias koj yuav loj {- qhov chaw ntim khoom me me, nws raug pom zoo kom zam nws cov qauv kev puas tsuaj rau cov qauv siv lead ua kom tsis txhob muaj kev puas tsuaj rau cov qauv siv lead ua kom tsis txhob muaj kev puas tsuaj rau cov qauv siv lead ua kom tsis txhob muaj kev puas tsuaj rau cov qauv siv lead ua ke kom tsis txhob muaj kev puas tsuaj rau cov qauv siv lead ua kom tsis txhob muaj kev puas tsuaj rau cov qauv siv lead ua kom tsis txhob muaj kev puas tsuaj rau cov qauv siv lead ua kom tsis txhob muaj kev puas tsuaj rau cov qauv siv lead ua ke kom tsis txhob muaj kev puas tsuaj rau cov qauv siv lead ua kom tsis txhob muaj kev puas tsuaj rau cov qauv siv lead ua kom tsis txhob muaj kev puas tsuaj rau cov qauv siv lead ua kom tsis txhob muaj kev puas tsuaj rau cov qauv siv lead ua kom tsis txhob muaj kev puas tsuaj rau kev ua kom puas.
Kev sib raug zoo ntawm cov tshuaj chemical thiab ruaj khov
Molecular qauv yam ntxwv
Cov qauv molecular ntawm acp - 105 yog c16h1919197, nrog molecular ceeb thawj ntawm 290.79, thiab nws yog rau cov khoom sib xyaw. Nws cov qauv tshuaj yog txawv ntawm cov tshuaj steroid thiab muaj cov kev xaiv siab. Txawm li cas los xij, tus qauv no kuj ua rau nws nkag siab txog cov kev mob ib puag ncig thiab cuam tshuam yooj yim los ntawm qhov kub thiab txias, av noo thiab lub teeb.
Purity thiab impurities
Cov hmoov ntawm cov siab purity (xws li loj dua lossis sib npaug ntawm 98%) muaj kev ruaj khov zoo dua. Impurities yuav ua raws li catalysts kom nrawm qhov kev ua tsis txaus siab. Yog li ntawd, siab -}}}}}}}}}}}} Yuav tsum tau los ntawm cov channel tsis tu ncua, thiab saib xyuas yuav tsum tau them nyiaj dawb huv thaum lub sijhawm cia.
Cov kev sib tw rau kev ruaj khov los ntawm ib puag ncig cov xwm txheej
Kev hloov pauv kub
Kev hloov pauv hauv kev cia kub nyob rau hauv cia kub tuaj yeem ua rau muaj kev cuam tshuam rau lub zog hluav taws xob ntawm Acp-105 molecules, nce kev pheej hmoo ntawm kev ua tsis taus. Piv txwv li, yog tias cov neeg mob tub yees tsis ruaj khov, cov khoom yuav qee qhov poob nws txoj hauj lwm poob zoo vim tias qhov ntsuas kub nce ntxiv.
Vaum thiab Ya Tshuaj
Acp-105 yog me ntsis soluble hauv cloroform, ethyl acetate thiab methanol, qhia tias nws yog rhiab rau ya raws. Ib puag ncig huab cua yuav ua rau nws nqus cov dej noo thiab cov qog ua haujlwm lossis yauv ua cov dej hiav txwv boed, txo nws cov haujlwm.
Teeb thiab Oxidation
Lub teeb kis tau yuav ua rau cov duab - oxidation cov tshuaj tiv thaiv ntawm acp {}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}} Yog li ntawd, ntim cia yuav tsum yog lub teeb pom kev kom tsis txhob muaj kev coj ua kom pom tseeb.
Kev Nyab Xeeb thiab soj ntsuam
Kev kuaj xyuas tsis tu ncua
Thaum lub sij hawm ntev - sij hawm} Cia cov txheej txheem khaws cia, nws raug pom zoo kom tsis tu ncua ntsuas qhov kev coj dawb huv thiab kev ua si ntawm acp - 105. Cov ntsiab lus hloov tuaj yeem ntsuas los ntawm cov hau kev xws li kev ua kom zoo ua kua chromatography (HPLC) los xyuas kom cov khoom lag luam zoo.
Kev ruaj khov cov ntaub ntawv siv
WSEE cov khoom xa tuaj yeem cov ntaub ntawv lub sijhawm ruaj khov, xws li "lub neej" txee lub neej ntawm 24 lub hlis nyob rau hauv 24-8℃cov kev mob ". Cov neeg siv tau tuaj yeem hais txog cov ntaub ntawv no thiab, sib xyaw ua ke nrog lawv tus kheej cov chaw khaws cia, tsim kev npaj lawv cov phiaj xwm.
Kev Tswj Xyuas Kev Ruaj Ntseg Hauv Cov Ntawv Thov Siv
Kev sim ua haujlwm tshwj xeeb
Thaum npaj cov kev daws teeb meem, tsim nyog raws li DMSO) yuav tsum tau siv thiab siab {{0} {{0} {{0} {{0} {{0} {{0} {{0} {{0} {{0} {{0} {{0} {{0} {} Qhov Kub Kom Muaj Tsawg Kom Tsis txhob Kom Muaj Tsawg Dua. Nws raug nquahu kom siv ib qho 0.22μm lim memtrane rau kev ua kom tsis muaj menyuam. AliTot thiab khaws cia kev daws teeb meem los tiv thaiv kev rov ua kom khov thiab yaj.
Kev Nyab Xeeb thiab Ua Raws
ACP-105 yog rau kev tshawb fawb tshawb fawb tsuas yog tsis yog rau kev kho mob, cov txiaj ntsig tshuaj lossis khoom siv tau. Thaum kev ua haujlwm, kev kuaj xyuas kev nyab xeeb txoj cai yuav tsum tau ua raws kom tsis txhob muaj kev sib chwv cov tawv nqaij thiab nqus tau hmoov av.
Cov lus qhia rau kev txhim kho kev ruaj khov
Txhim kho qhov chaw cia khoom
Siv cov tub yees siv kub nrog kev tswj qhov kub thiab txias thiab lub teeb {- thaiv kev ua haujlwm kom ntseeg tau tias muaj cov xwm txheej ruaj khov. Nquag tshuaj xyuas cov khoom khaws cia kom tiv thaiv kev sib txawv kub.
Xaiv cov neeg xa khoom kom zoo
Kev yuav khoom los ntawm cov neeg muab khoom uas muab cov ntaub ntawv ruaj khov thiab cov lus qhia cia kom ntseeg tau tias cov khoom lag luam zoo thiab tom qab muag khoom txhawb.
Tsim cov txheej txheem qauv
Tsim cov txheej txheem kev ua haujlwm (sops) rau kev cia, siv thiab saib xyuas ACP-105 los txo cov teeb meem kev ruaj khov tshwm sim los ntawm tib neeg.
Acp-105 Hmoov, raws li tus xaiv androgen receptor modulator (slar), muaj cov ntawv thov tseem ceeb muaj nuj nqis hauv kev tshawb fawb kev tshawb fawb. Txhawm rau kom nws cov kev ua tau zoo thiab kev ua ub no, kev tshawb fawb thiab nruj kev ntsuas txoj kev yuav tsum tau saws. Cov kab ke nram qab no nthuav tawm cov txheej txheem ntawm cov hmoov ntawm no xws li tshuaj ntsuam xyuas cov tshuaj lom neeg xws li tshuaj xyuas kev mob plab thiab tshuaj tsom xam.
Cov qauv tshuaj pov thawj
Proton Nuclear Sib Nqus Revonance Spectroscopy (HNMR)
HNMR yog cov txheej txheem tseem ceeb rau kev pom zoo cov qauv tshuaj ntawm ACP-105. Los ntawm kev kuaj pom kev sib raug zoo ntawm hydrogen ntawm hydrogen ntawm hydrees atoms hauv ib pawg molecule, cov haujlwm muaj peev xwm txheeb xyuas thiab pab pawg ua haujlwm tau tseeb. Piv txwv li, cov mis molecular ntawm acp-105 yog c16h1919cln2o. HNMR tuaj yeem tshab cov cim ntawm lub teeb liab ntawm nws lub nplhaib Barzene, Chororine atom, nitrogen harocyclic, thiab lwm yam.
Pawg Tshaj Tawm Kev Ntsuam Xyuas (MS)
Pawg Spectrometry siv los txiav txim siab cov molecular hnyav ntawm acp -}} 105 thiab cov ntaub ntawv ntawm nws cov khib ions. High-decorution cass spectrometry (HRMS) tuaj yeem txiav txim siab txiav txim siab cov molecular hnyav (290.79) thiab pab txhawm rau txheeb xyuas cov qauv molecular. Piv txwv li, tus lej lej ntawm Acp-105 yog 899821-23-9, thiab huab hwm coj spectrometry cov ntaub ntawv tuaj yeem sib phim nrog nws cov mis.
Kev Kuaj Purity Purity
Kev ua kom zoo ua kua chromatography (HPLC)
HPLC yog txoj kev txheem rau kev kuaj pom lub purity ntawm acp - 105. Siab - Desolution sib cais tuaj yeem ua tiav los ntawm kev xaiv cov ntsuas cov chwv cov chwv tsawg thiab mobile. For example, by using a C18 reversed-phase chromatographic column and gradient elution with methanol-water as the mobile phase, it is possible to detect whether the purity of the main peak of ACP-105 reaches above 98% and identify impurity peaks.
Nyias - txheej txheej chromatography (TLC)
TLC, raws li kev soj ntsuam sai sai, tuaj yeem siv rau kev txiav txim siab txiav txim siab txog kev coj dawb huv ntawm acp {}} 105. Los ntawm kev xaiv tus neeg sawv cev tsim nyog (xws li chloroform - methanol sib tov), thiab saib tus naj npawb ntawm pob thiab rf qhov tseem ceeb, nws tuaj yeem yog tus qauv muaj impurities.
Kev Ntsuam Xyuas Kev Ruaj Ntseg
Kev Ntsuam Xyuas Kev Ntsuas Ruaj Ntseg
Tso cov hmoov hauv qab kub siab (40 degree) thiab cov av noo (75% kev ruaj ntseg los ntawm hnmr, thiab nws txee lub neej yog ntsuas.
Ntev - sij hawm cia khoom ruaj khov
Nquag sim cov kev coj dawb huv thiab kev ua yeeb yam ntawm acp {}}}} 105 nyob rau hauv cov neeg muaj kev pom zoo (xws li -20℃ntawm lub teeb). Piv txwv li, nws ruaj ruaj ruaj ruaj ruaj ruaj los ntawm HPLC thiab xws li androgen recepting kev sim nyob rau hauv lub txee lub neej.
Kev Ntsuam Xyuas Kev Ua Haujlwm Kev Ntsuas
Androgen Receptor Conding Kev Sim
Lub -}} 105 nrog cov nqi rigand (xws li siv xov tooj cua Ligand lossis cov tshuaj fluorescent polarization. Piv txwv li, lub pec50 ntawm Acp-105 tiv thaiv tsiaj qus ar thiab T877A Mutant Ar yog 9.0 thiab 9.3 hais tias nws muaj siab xaiv thiab muaj zog kev ua si.
Kev sim ntawm Cell
Hauv cov qauv xov tooj (xws li CV - 1 cell lossis c2c12 ua kom muaj kev sib txuam ntawm ACP-105 rau ntawm Andt assister lossis tus kws tshaj xo ente assay. Piv txwv li, txheeb xyuas lub Luciferase kev ua si lossis cov lus qhia ntawm tes nws tsim los xyuas nws cov kev ua haujlwm roj ntsha.
Lwm txoj kev analytical
Kev ua kom zoo ua kua chromatography (HPLC)
HPLC yog siv rau kev txheeb xyuas kom muaj tseeb ntawm cov kev coj dawb huv thiab cov ntsiab lus ntawm acp - 105. Piv txwv li, los ntawm kev siv C18 Chromatographic kem thiab Acetonitrile kem thiab tshuaj xyuas} dej yog cov khoom lag luam uas tau sib cais (huv si ntau dua lossis sib npaug ntawm 98%).
Pawg Tshaj Tawm Kev Ntsuam Xyuas (MS)
Pawg Spectrometry siv kom paub meej tias cov lus hnyav molecular thiab cov thooj ion cov ntaub ntawv ntawm acp-}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}. Piv txwv li, los ntawm Electrospray ionization loj loj spectrometry (ESI-MS), [M + H] + tuaj yeem tau txais kev paub meej ntxiv nws txoj kev hnyav.
Daim ntawv thov thiab qhov tseem ceeb ntawm cov qauv ntsuas
Kev Tswj Xyuas Zoo
Los ntawm cov qauv kev tsom xam saum toj no, qhov zoo ntawm Acp-105 hmoov tuaj yeem nkag siab tau tias nws ua tau raws li cov qauv kev tshawb fawb lossis kev siv khoom siv. Piv txwv li, kev sib xyaw ua ke ntawm HNMR thiab HPLC tuaj yeem ua tiav cov qauv thiab kev tiv thaiv cov khoom lag luam hauv cov txheej txheem sim.
Kev kawm ruaj khov
Kev nrhiav kom tsis tu ncua ntawm Acp-105 thaum lub sijhawm cia los ntawm HPLC thiab HNMR tuaj yeem saib xyuas nws cov kev hloov pauv thiab cov kev hloov cov ntaub ntawv, muab cov ntaub ntawv txhawb nqa rau kev cia siab. Piv txwv li, yog tias ib qho kev hloov pauv ntawm kev coj dawb huv lossis kev hloov cov qauv raug kuaj pom, cov neeg muaj kev cia yuav tsum tau hloov kho kom sai.
Pov thawj ntawm kev ua haujlwm roj ntsha
Kev ua haujlwm roj ntsha ntawm acp - 105 tau txheeb xyuas qhov kev sim ntawm tes lossis tsiaj cov qauv los xyuas kom meej tias nws cov kev xav tau zoo tau ntsib kev cia siab. Piv txwv li, los ntsuas kev ntsuas lub PEC50 tus nqi ntawm Acp-105 rau Androgen Receptors (xws li 9.0 rau T877A Mutant AR), nws xaiv thiab kev ua tau zoo tuaj yeem raug ntsuas.
Kev ua haujlwm biological
Tub Ntxhais Kev Ua Ntsuas
Acp {-} 105 yog ib qho kev sib cav ntawm cov lus qhia tsis muaj suab stereptor modulator (sarm). Nws cov roj ntsha ua tau tiav los ntawm cov txheej txheem hauv qab no:
Hom Phiaj Xaiv:
Lub Pec₅₀ tus nqi rau cov tsiaj qus - Hom Androgen Receptor (AR WT) yog 9.0 (qhia txog ib qho siab rau lub ntuj ar.
Lub Pec₅₀ tus nqi rau T877A Mutant Ar yog 9.3 (piv txwv li, EC₅₀ ≈ ≈ ≈ ≈ ≈ ≈ ≈), qhia ib qho kev ua kom muaj zog muaj peev xwm rau qee cov tshuaj {} {tiv taus merrants.
Xaiv cov txiaj ntsig: piv rau cov tshuaj steroid ib txwm, Acp-105 tseem ceeb txo cov ntaub so ntswg xws li kev mob prostate xws li cov plaub hau poob thiab pob txuv.
Nkaus hom:
Raws li ib nrab agonist, acp-105 mimics cov txuj ci anaboob ntawm cov nqaij mos thiab pob txha, txhawb kev loj hlob protein thiab cov leeg nqaij.
Hauv cov kev sim tsiaj, nws cov nyhuv ntawm kev txhawb cov leeg nqaij hypertrophy piv rau cov prostosterone yog tsuas yog 1/10 ntawm cov testosterone tsuas yog.
Hauv vitro thiab hauv vivo kev ua si pov thawj
Hauv kev sim vitro
Cell tej dej num:Nyob rau hauv ar - transfection cell cov kab, acp}}}}}}}}}}}}} aix) ncav 80% ntawm cov tes testosterone.
Metabolic stability:Hauv tib neeg lub siab hlwb, ib nrab - lub neej} lub neej ntawm Acp-105 yog 5 teev, thiab ntau pawg neeg niaj hnub yuav tsum muaj kev tswj ntshav tshuaj.
Hauv Vivo kev sim
Cov leeg qauv qauv:Hauv cov lej nas ua qauv, Acp-105 (10 mg / kg / hnub, orally) ua rau qhov hnyav ntawm cov tshuaj zoo ib yam li ntawm testosterone.
Neuroprotective nyhuv:Nyob rau hauv irradiation kev ua qauv nas, acp {}}}}}}
Cwj pwm cuam tshuam:Acp-105 txhim kho qhov kev ntshai txias teb muaj peev xwm muaj cov nas, tejzaum nws los ntawm kev cai ntawm hippocampal platity.
Cov yam ntxwv ntawm cov chaw ua ke
So
Lub solubility hauv dmo yog ntau dua los yog sib npaug rau 60 mg / xav tau ultrasonic (yuav tsum tau npaj ultrasonic, haum rau kev npaj hauv Vivo Administron tswj kev daws teeb meem.
Kev tso khoom ruaj khov
Cov hmoov foos: {{{- 20℃rau lub sijhawm ntev cia nyob rau hauv kev tiv thaiv ntev, nrog lub sijhawm siv tau ntawm 2-3 xyoos;
Kev daws tom qab kev daws teeb meem: -80℃rau cia, nrog lub sijhawm siv tau ntawm 1 xyoos (zam dua qhov khov thiab yaj).
Kev Nyab Xeeb Kev Nyab Xeeb thiab Kev Nyab Xeeb Kev Nyab Xeeb
Kev Tshawb Fawb Computer Simulation:
Kwv yees los ntawm cov cuab yeej xws li Instrab thiab Propetlab thiab propetlab thiab prop-105 tsis muaj qhov tseem ceeb mob Toxicity (LD₅₀), thiab tsis muaj qhov muaj kev phom sij txaus ntshai rau lub siab thiab raum.
Kev Nyab Xeeb Kev Nyab Xeeb Kev Nyab Xeeb: Tshuaj ntsuab channel inhibition aws tsis muaj kev pheej hmoo ntawm arrhythmia (ict> 30 μm).
Genotoxicity:
Ames kev xeem kwv yees cov txiaj ntsig tsis zoo, qhia tsis muaj mutagenicity.
Daim Ntawv Thov Lub Peev Xwm thiab Kev Tshawb Fawb Kev Tshawb Fawb
Kev Tshawb Fawb Txog Kev Kawm Txuj Ci
Cov peev txheej kho cov tshuaj rau cov leeg atrophy (xws li cov leeg nqaij, mob cancia cachia).
Tus neeg sib tw cov tshuaj rau cov pob txha caj qaum, txhawb cov pob txha los ntawm kev ua kom pob txha ar.
Cov Kev Tshawb Fawb Ua Si
Raws li cov khoom siv hluavtaws, ACP-105 yuav raug tsim txom-105 yuav raug tsim txom ua tus sawv cev Anabolic, tab sis nws cov nqaij mos txwv yuav txo cov kev mob tshwm sim ntawm cov tshuaj steroids.
Neuroscience
Tshawb nrhiav nws cov kev kho tus nqi rau cov kab mob neurodegenerative xws li Alzheimer tus kab mob thiab mob stroke.
Cim npe nrov: Acp-105 Hmoov, Tuam Tshoj Chaw Tsim Tshuaj, Chaw Tsim Tshuaj, Hoobkas, lag luam Wholesale, yuav, nqe, loj, loj, rau muag