Hauv thaj chaw kho mob ntawm myeloproliferative neoplasms thiab cov kab mob inflammatory, aberrant activation ntawm JAK-STAT signaling pathway yog ib qho tseem ceeb molecular tshwm sim tsav kab mob kev loj hlob.Ruxolitinib Phosphate Hmoovyog tshuaj phosphate daim ntawv ntawm ruxolitinib, belongs rau pyrrolo[2,3-d]pyrimidine me me molecule inhibitor chav kawm. Raws li thawj pom zoo JAK inhibitor, ruxolitinib sib tw khi rau ATP- khi hnab ris ntawm JAK1 thiab JAK2, thaiv cov phosphorylation thiab nuclear translocation ntawm STAT proteins, yog li inhibiting JAK- STAT txoj hauv kev- kho kom haum xeeb pro-inflammatory cytokine signaling.
🔬 Molecular Archives hauv Phosphate Forms
Ruxolitinib Phosphate Hmoovmuaj tag nrho cov mis molecular C₁₇H₁₈N₆・H₃O₄P thiab tus txheeb ze molecular loj ntawm 404.36. Ib leeg-cov qauv siv lead ua diffraction tag nrho txo cov pyrrolopyrimidine fused core, nruab nrab pyrazole linker, thiab lub davhlau ya nyob twg R-configuration chiral cyclopentadienylpropionitrile sab saw. Qhov sib ntxiv ntawm ib qho molecule ntawm phosphate tsim ib qho ionicly ruaj khov ntsev- hom crystallization bent stereoconformity. Lub molecule tsuas muaj ib qho chiral carbon, thiab tsuas yog R stereoconformation muaj ua tiav kinase binding kev ua. Tom qab racemization, affinity rau JAK2 binding txo los ntawm ntau tshaj 94%. Tom qab batch purification, purity ntawm chiral active conformation tseem nyob ruaj khov saum 99.8%.
Tag nrho cov molecule nthuav tawm meej kev ua haujlwm faib. Lub core pharmacodynamic nucleus yog pyrrolopyrimidine aromatic diazoxide nplhaib. Ntau cov nitrogen atoms nyob rau hauv lub nplhaib tsim ib tug multi-layered hydrogen- bonded qauv nrog cov Glu thiab Leu amino acid residues nyob rau hauv lub kinase pob khawm, tsim lub core moj khaum uas sib tw occupies ATP substrate binding qhov chaw. Lub hauv paus pyrazole tsib-nplhaib koom ua ke ua rau qhov nqaim, qhov tsis muaj dej hauv lub hnab kinase, ua kom lub sijhawm nyob hauv lub sijhawm nrog cov protein ntau. Lub davhlau ya nyob twg chiral cyclopentyl pawg, ua ke nrog ib pawg propionitrile polar cyano, tsim ib qho amphiphilic balanced side chain, meej meej sib txawv ntawm kab noj hniav ntawm JAK1 / JAK2 thiab JAK3 / TYK2, txo qhov kev pheej hmoo ntawm dav -spectrum immunosuppression. Dawb phosphate pawg tsim ionic bonds nrog cov nitrogen atoms ntawm cov molecule, kom kov yeej cov kev txwv ntawm dawb alkali dej solubility. Cov ntsev no-zoo li cov qauv yog qhov kev txiav txim siab ntawm cov qauv tsim rau siab solubility thiab siab cellular permeability.
Feem ntau cov dawb hauv paus JAK inhibitors muaj cov dej solubility tsis zoo, thiab molecular nag lossis daus nyob rau hauv vitro hematopoietic cell incubation systems ua rau muaj kev hloov pauv hauv cov ntaub ntawv enzyme. Cov khoom no, nyob rau hauv nws daim ntawv phosphate, tso siab rau ionic bonds los txhim kho polarity. Kinetic tsom xam qhia tau hais tias cov khoom no muaj ib tug IC50 ntawm 2.7 nM rau JAK2, 4.5 nM rau JAK1, thiab nws inhibitory kev ua si tawm tsam JAK3 yog ntau tshaj 300 lub sij hawm tsis muaj zog. Nws nthuav tawm kev thaiv ib txhij ntawm ob qho isoforms nrog qis qis heev - phiaj xwm kev pheej hmoo. Qhov tshwj xeeb nitrogen atom kev npaj ntawm pyrrolopyrimidine heterocycle, ua ke nrog cov phosphate ion, ua tiav qhov sib npaug ntawm kev ua haujlwm siab thiab solubility siab -ib qho txiaj ntsig zoo ntawm lub cev molecules dawb tsis tuaj yeem ua tiav.
Lub nplhaib pyrrolopyrimidine conjugated nitrogen-muaj heterostructure nthuav tawm cov tshuaj lom neeg zoo heev. Lub nplhaib uas muaj ntxhiab tsis yooj yim hydrolyzed unsaturated bonds, ua rau nws tiv taus lub nplhaib - qhib degradation thaum batch cia ntawm chav tsev kub. Nws tsis muaj cov pab pawg oxidized los yog hydrolyzed yooj yim xws li thiol pawg lossis ester bonds, tiv thaiv oxidative cross-txuas thiab nag lossis daus txawm tias tom qab ntev - lub sij hawm tso rau hauv pob txha pob txha qia cell, macrophage, thiab daim tawv nqaij keratinocyte kab lis kev cai xov xwm. Qhov no tshem tawm qhov xav tau ntxiv solubilizing thiab stabilizing cov neeg ua haujlwm thaum tsim lub sijhawm ntev - lub sij hawm inflammatory thiab hematopoietic proliferation pathological qauv, tsis txhob cuam tshuam los ntawm exogenous reagents nrog STAT phosphorylated protein immunoblotting fluorescence kuaj pom cov cim. Ib txheej ntawm molecular binding kinetics cov ntaub ntawv qhia tau hais tias tshem tawm homologous derivatives ntawm pyrrolopyrimidine aromatic nplhaib tsub kom lub dissociation tus nqi ntawm cov molecule los ntawm JAK kinase tenfold, kiag li tshem tawm cell proliferation inhibition kev ua. Lub aromatic fused heterocycle yog ib qho irreplaceable core functional unit rau ntev -lub sij hawm ruaj khov khi ntawm lub hom phiaj enzymes.
Phosphate ions ho optimize molecular solubility; Cov hmoov ua tiav qhov solubility txog li 36 mg / mL hauv dej ntshiab ntawm chav tsev kub. High -concentration hematopoietic cell incubation solutions qhia tias tsis muaj flocculent agglomeration los nag lossis daus, tshem tawm qhov xav tau rau siab -proportion solubilizing agents kom muaj kev sib txawv ntawm molecular dispersion. Lub nplhaib hydrophobic ntawm lub davhlau ya nyob twg cyclopentane thiab pawg polar cyano ntawm propionitrile sib npaug tag nrho cov lipids -dej faib coefficient LogP=2.19. Nws tuaj yeem nkag mus rau pob txha pob txha stromal cell membrane, stratum corneum ntawm daim tawv nqaij, thiab phospholipid bilayer ntawm immune lymphocytes. Ib qho kev sib xyaw ua ke tuaj yeem tsim ib qho qauv sib xyaw ua ke ntawm cov kab mob sib txawv ntawm cov pob txha pob txha hematopoiesis, kev tiv thaiv kab mob hauv lub cev, thiab cov kab mob hauv cheeb tsam ntawm daim tawv nqaij, tsis tas yuav muaj ntau yam khoom siv raw los txo cov kev cuam tshuam sib txawv.
⚙️ ATP kev sib tw dual thaiv ntawm JAK1 / JAK2 tswj hematopoiesis
Ruxolitinib Phosphate Hmoov, tso siab rau nws cov dej siab heev -soluble phosphate-raws li amphiphilic heterocyclic me me molecular qaum, ywj siab nkag mus rau hauv cov cell membranes ntawm cov pob txha stromal hlwb, macrophages, tawv nqaij keratinocytes, thiab lymphocytes. Cov molecule tsis tu ncua yog coj mus rau hauv lub intracellular JAK1 / JAK2 kinase faib cheeb tsam. Tag nrho cov txheej txheem tswj hwm muaj plaub txoj hauv kev: ATP kev sib tw thaiv ntawm kinases, tag nrho inhibition ntawm STAT phosphorylation, ntes ntawm mutant hematopoietic clone proliferation, thiab downregulation ntawm ntau yam pro-inflammatory cytokines. Nws tsuas yog tsom rau JAK1 / JAK2 overactivated, nrog kev cuam tshuam tsawg heev rau JAK3 / TYK2, uas tswj kev tiv thaiv kab mob tseem ceeb. Qhov no txawv nws ntawm qhov dav -spectrum JAK inhibitors, uas ua rau muaj kev cuam tshuam loj rau neutropenia thiab kis kab mob thib ob.
Hauv tib neeg cov kab mob myeloproliferative, JAK2 V617F kev hloov pauv tsis tu ncua ua rau kinase, tsis tu ncua phosphorylating STAT5 transcription protein, tsav tsheb tsis zoo clonal expansion ntawm megakaryocytes thiab erythrocytes, inducing myelofibrosis thiab splenomegaly. Hauv cov tshuaj tiv thaiv kab mob autoimmune, graft - tiv thaiv - tus kab mob, thiab atopic dermatitis, JAK1 yog overactivated, tso tawm ntau cov pro-inflammatory yam xws li IL-6, TNF- , thiab IFN - , ua rau cov tawv nqaij puas thiab puas. Ob leeg ntawm cov txheej txheem pathological no yog nyob ntawm kev ua haujlwm tas li ntawm JAK-STAT signaling axis.
Ib qho nyuaj pyrrolopyrimidine heterocycle yog kos rau hauv ATP catalytic kab noj hniav ntawm JAK1 / JAK2 kinase. Cov nitrogen atom nyob rau hauv lub nplhaib tsim multilayer hydrogen bonds nrog amino acids nyob rau hauv lub kinase pob khawm. Phosphate ions ua rau kom cov intracellular concentration ntawm cov molecule, sib tw neeg coob coob tawm endogenous ATP substrate binding qhov chaw, yog li ua rau lub kinase poob nws catalytic muaj peev xwm mus phosphorylate STAT proteins. Nyob rau hauv vitro recombinant JAK enzyme isothermal incubation cov ntaub ntawv qhia tias tom qab plaub teev ntawm 0.05 μM hmoov cuam tshuam, JAK2-mediated STAT5 phosphorylation inhibition tus nqi yog 93%, thiab JAK1-mediated STAT3 phosphorylation inhibition tus nqi yog 89%. Qhov no tau rhuav tshem tag nrho cov kev pib pib cov cim ntawm hematopoietic proliferation thiab o ntawm cov noob caj noob ces ntawm qhov chaw ntawm kinase catalysis, thaiv lub voj voog txuas ntxiv ntawm cov kab mob pathological.
Tom qab ua tiav kev thaiv ntawm STAT phosphorylation txoj hauv kev, kev hloov pauv ntawm kev hloov pauv -cov noob muaj feem xyuam rau hematopoietic qia cell proliferation tau txo qis, lub voj voog ntawm tes ntawm qhov txawv txav ntawm hematopoietic clones raug ntes, thiab cov pob txha pob txha matrix collagen synthesis txoj hauv kev tau ib txhij ua haujlwm ntawm cov pob txha sib txuas ntxiv. Ntev - lub sij hawm isothermal incubation soj ntsuam cov ntaub ntawv ntawm peb - qhov ntev ntawm cov pob txha pob txha organoids pom tau tias tom qab 21 hnub ntawm kev cuam tshuam cov hmoov tsis tu ncua, qhov feem ntawm JAK2- mutant txawv txav hematopoietic hlwb poob los ntawm 62%, thiab splenomegaly - cuam tshuam cov cell tsis muaj zog. Luv-lub sij hawm nruab nrab ntawm cytokine{11}}raws li kev tiv thaiv- cov ntaub ntawv inflammatory ib leeg tsis tuaj yeem thaiv hematopoietic clone proliferation thiab tsis muaj kev cuam tshuam ntev hauv kev thim rov qab cov pob txha pob txha.
Ruxolitinib Phosphate Powder ib txhij thaiv JAK1 txoj hauv kev hauv lub cev tiv thaiv kab mob, txo qis cov qib transcriptional pro-inflammatory cytokine mRNA nyob rau hauv macrophages, T lymphocytes, thiab daim tawv nqaij keratinocytes, thiab txo tag nrho cov secretion ntawm IL-7} thiab TNF. Nws kuj inhibits kev tso tawm ntawm chemokines los ntawm daim tawv nqaij stratum corneum, alleviating lub zos khaus thiab erythematous lesions. Nyob rau hauv ib qho hauv vitro co-culture qauv ntawm cytokine cua daj cua dub, cov hmoov tuaj yeem cuam tshuam cov teeb liab hloov pauv ntawm ntau theem, tiv thaiv inflammatory yam tseem ceeb los ntawm kev tsis tu ncua ntawm lub cev epithelium thiab cov ntaub so ntswg ntawm daim tawv nqaij, thiab tsim nyog rau kev tsim kho ib txhij ntawm ob lub hauv vitro pathological systems: lub cev tiv thaiv kab mob overreaction thiab cov tawv nqaij hauv zos.
🧫 Ntshav Immunopharmacology tau ua tiav hauv qhov loj
Qhov tseem ceeb ntawm kev sivRuxolitinib Phosphate Hmoovyog concentrated nyob rau hauv batch tsom xam ntawm JAK kinase subtype pathways. Cov hmoov no yog siv los ua tus qauv zoo tswj substrate rau batch tsim nyob rau hauv vitro cell thiab peb -dimensional pob txha pob txha thiab daim tawv nqaij organoid qauv hais txog JAK2 mutant pob txha pob txha proliferation, qog qia cell proliferation, graft-vim-tus kab mob, thiab keratinocyteitis nyob rau hauv atopic dermatitis.
JAK raw cov ntaub ntawv feem ntau yog nyob rau hauv daim ntawv dawb dawb nrog cov dej tsis zoo solubility, thiab molecular nag lossis daus nyob rau hauv vitro cell systems tuaj yeem ua rau muaj kev hloov pauv hauv cov ntaub ntawv ua haujlwm. Cov khoom no, nyob rau hauv nws daim ntawv phosphate, yog ruaj khov thiab muaj peev xwm tag nrho replicate cov pathological hloov ntawm hematopoietic abnormalities ua ke nrog systemic thiab lub zos ntawm daim tawv nqaij o, tshem tawm cov ntaub ntawv paug los ntawm dawb cov ntaub ntawv raw. Parallel zoo tswj cov ntaub ntawv los ntawm ntau cov ntshav immunopharmacology batch txoj kev loj hlob platforms qhia tau hais tias siv cov hmoov no los tsim kinase blockade qauv txo qhov yuam kev tus nqi ntawm protein phosphorylation thiab cell colony suav cov ntaub ntawv los ntawm 66%, tshem tawm qhov xav tau rau ntau yam dawb paug tswj kom paub qhov txawv ntawm peb ywj siab tswj cov teeb liab ntawm hematopoietic kab mob, kev loj hlob ntawm daim tawv nqaij, kev loj hlob ntawm daim tawv nqaij. txheej txheem ntawm kev txheeb xyuas cov txheej txheem molecular ntawm cov ntshav tiv thaiv kab mob.
- JAK1/JAK2/JAK3 kinase subtype differentiation detection batch reference standard
- JAK2 mutant myelofibrosis peb- qhov ntev ntawm cov pob txha pob txha organoid txheem raw khoom
- Cytokine cua daj cua dub, graft-vim-tus tswv tsev tiv thaiv kab mob hauv vitro batch cuam tshuam substrate
- Atopic dermatitis keratinocyte chronic inflammatory pathology peb -dimensional skin organoid material
Batch kev sib piv kev ntsuas ntawm cov hlau lead active molecules rau cov pob txha pob txha proliferation thiab tiv thaiv kab mob yog qhov thib ob loj tshaj plaws daim ntawv thov scenario rau hmoov. Txoj kev loj hlob ntawm ntau yam tshiab heterocyclic JAK ntsev- hom inhibitors, anti-fibrotic me me molecules, thiab tiv thaiv - daim tawv nqaij peptides tag nrho sivRuxolitinib Phosphate Hmoovraws li ib tug unified efficiency reference standard. Cov ntaub ntawv los ntawm cov khoom siv hauv vitro sib xyaw hematopoietic immune cell co- kab lis kev cai kuaj pom pom tias cov qauv molar concentration hmoov tuaj yeem txo qhov kev nthuav dav ntawm mutant hematopoietic clones ze li 70%. Raws li tus qauv siv batch, nws muaj peev xwm ntsuas lub zog ntawm dual kinase thaiv, tiv thaiv -fibrosis, thiab los tiv thaiv - inflammatory los ntawm cov tshuaj sib txawv ntawm cov pob txha active molecules, ua rau nws ib tug indispensable standard ntsev- hom crystalline hmoov rau qhov loj - teev thawj zaug tshuaj ntsuam ntawm molecules JAK.
Cov hmoov no tau siv dav hauv kev tshuaj ntsuam batch ntawm cov nquag molecules rau kev puas tsuaj los ntawm hematopoiesis ua ke nrog cov tawv nqaij o. Nruam isothermal incubation tau siv los tsim kev ruaj khov JAK1/JAK2-activated pob txha pob txha-keratinocyte co- kab lis kev cai rau kev soj ntsuam cov txiaj ntsig zoo ntawm ntau yam heterocyclic derivatives thiab cov txiaj ntsig ntuj tso rau ntawm qhov txawv txav hematopoiesis thiab daim tawv nqaij mob. Cov qauv pathological nyuaj yuav tsum muaj qhov ruaj khov thiab tswj tau tom qab ntawm dual kinase overactivation. Ib leeg -lub hom phiaj tiv thaiv- mob thiab tiv thaiv- cov ntaub ntawv nyoos tsis tuaj yeem ua tiav cov txheej txheem tseem ceeb ntawm kev puas tsuaj rau ntau lub cev. Cov hmoov ib txhij tsim ib tug triple phenotype ntawm uncontrolled hematopoietic clones, systemic o, thiab daim tawv nqaij mob. Tag nrho cov kev ntsuam xyuas batch yuav tsum cia siab rau siab -purity, impurity-dawb ntsev- hom hmoov los tswj cov qauv kev ruaj ntseg. Cov lej ntawm cov nplhaib heterocyclic- qhib thiab phosphate dissociation impurities tuaj yeem cuam tshuam nrog Western blot fluorescence signals, ua rau muaj kev cuam tshuam hauv cov ntaub ntawv sib piv cov tshuaj loj loj.
Qhov kev ntsuam xyuas hauv vitro batch rau cov kab mob ntev ntev - tiv thaiv - tus kab mob (GVHD) tom qab hloov pauv tau dav siv Ruxolitinib Phosphate Powder. Tshaj - ua kom cov allogeneic lymphocytes tso tawm ntau ntawm cov kab mob inflammatory ua rau lub cev, thaum cov hmoov blocks JAK1 signaling kom sib npaug lub cev tiv thaiv kab mob homeostasis. Qhov no yog siv rau batch kev sib piv ntawm kev hloov pauv - tiv thaiv active molecules. Cov ntaub ntawv los ntawm hauv vitro allogeneic lymphocyte co- kev soj ntsuam kab lis kev cai qhia tau hais tias qhov kev faib ua feem ntawm lub hom phiaj hauv nruab nrog cev -infiltrating lymphocytes txo qis los ntawm 58% tom qab kev cuam tshuam cov hmoov, ua rau nws yog ib qho kev mob siab rau cov txheej txheem substrate rau batch tsom xam ntawm kev hloov lub cev tiv thaiv kab mob.
🔬 Pyrrolopyrimidine ntsev- hom pob txha hloov kho thiab hloov kho tshiab
Kev nce qib tseem nyob hauv qhov chaw-Kev hloov kho tshwj xeeb ntawm cov tub ntxhais pyrrolopyrimidine aromatic heterocycle ntawm Ruxolitinib Phosphate Powder. Kho tus naj npawb ntawm hydrogen bonds los ntawm kev hloov cov fluorine thiab methyl substituents ntawm lub nplhaib tswj cov molecule qhov inhibitory tshuav nyiaj li cas tawm tsam JAK1 / JAK2. Lub hauv paus txheej txheem heterocycle nthuav tawm qhov sib npaug inhibitory zog tawm tsam ob hom kinases. Lub vev xaib- tshwj xeeb halogenated aromatic derivatives tuaj yeem cuam tshuam rau JAK2 myeloproliferation inhibition lossis JAK1 cov kev cai ntawm daim tawv nqaij o, yoog rau cov qauv sib txawv ntawm cov kab mob uas tsom mus rau hematologic malignancies thiab dermatitis. Hloov kho phosphate hmoov yog maj mam muab tso rau hauv cov txheej txheem kev sib piv batch rau ntev - kev cuam tshuam hauv myelofibrosis thiab mob atopic dermatitis.
Ruxolitinib Phosphate Hmoov, nrog nws dual -txoj kev sib txuas ntawm cov pob txha pob txha thiab daim tawv nqaij, sawv cev rau txoj hauv kev ua kom zoo tshaj plaws tam sim no tab tom nrhiav. Tus thawj cyclopentadienoic acid sab saw tsis muaj kev paub tshwj xeeb rau cov pob txha pob txha matrix thiab stratum corneum, uas ua rau muaj kev faib tawm thoob plaws hauv lub cev thiab kev txwv sab saud rau hauv zos ua kom muaj txiaj ntsig zoo ntawm qhov txhab. Los ntawm grafting pob txha pob txha matrix-affinity luv peptides thiab stratum corneum- targeting fatty acid fragments mus rau sab nrauv ntawm lub propionitrile terminal chain, kev thauj thiab tuav efficiency ntawm molecules nquag khaws cia nyob rau hauv cov pob txha pob txha lesions thiab daim tawv nqaij o cheeb tsam. Hauv vitro peb- qhov ntev ntawm cov pob txha pob txha thiab daim tawv nqaij organoid permeation tswj cov ntaub ntawv qhia tau hais tias cov hmoov hloov nrog grafted tsom fragments tsub kom qhov zoo molecule enrichment concentration nyob rau hauv cov ntaub so ntswg hlwb los ntawm 2.8 zaug. Raws li tib lub kinase thaiv cov nyhuv, cov molar concentration ntawm raw cov ntaub ntawv siv yuav raug txo los ntawm 60%, txo tej zaum yuav me ntsis metabolic cuam tshuam los ntawm ntev - lub sij hawm raug ntawm siab -concentration heterocyclic me me molecules rau ib txwm hematopoietic thiab epidermal hlwb. Qhov no ua rau nws tsim nyog rau kev loj hlob ntawm - nplai, qis- koob tshuaj, ntev- ua rau cov ntshav thiab cov tawv nqaij ua rau cov kab mob sib kis.
Ntau- txoj hauv kev fusion hybrid molecules tau dhau los ua qhov kev tsim kho tshiab. Cov tub ntxhais pyrrolopyrimidine dual JAK thaiv cov pob txha heterocyclic ntawm Ruxolitinib Phosphate yog covalently txuas nrog cov pob txha pob txha los tiv thaiv -fibrotic heterocycle thiab daim tawv nqaij antioxidant phenolic hydroxyl fragment ntawm saj zawg zog alkyl chains. Qhov no tsim ib qho molecule nrog triple enhanced zog: dual JAK kinase thaiv, pob txha pob txha collagen degradation, thiab daim tawv nqaij dawb radical scavenging. Ib qho hybrid molecule ib txhij tuaj yeem tswj peb txoj hauv kev nyuaj pathological - mutant hematopoietic clones, pob txha pob txha interstitial fibrosis, thiab mob ntev ntawm daim tawv nqaij - yam tsis tas yuav tsum muaj ntau yam khoom xyaw. Cov khoom sib xyaw ua ke ntau- cov khoom xyaw muaj feem cuam tshuam rau cov nqi hluav taws xob thiab kev sib cuam tshuam hydrophobic uas ua rau tsis muaj zog ntawm kev ua haujlwm ntawm ib tus neeg. Lub tandem fusion hybrid molecule tsis txhob cuam tshuam cov teeb meem antagonism. Nyob rau hauv vitro pob txha pob txha- daim tawv nqaij ua ke peb- qhov nruab nrab kab lis kev cai organoid kab lis kev cai, hematopoietic daim tawv nqaij homeostasis kho kev ua tau zoo yog ze li 40% siab dua li tus thawj Ruxolitinib Phosphate Powder, ua kom yooj yim cov txheej txheem tsim cov txheej txheem rau kev cuam tshuam cov txheej txheem ntawm cov pob txha pob txha proliferation.
Qhov zoo tshaj plaws Ruxolitinib Phosphate Powder, ib qho tshuaj tiv thaiv rau qhov tsis muaj zog acidic microenvironment ntawm cov kab mob inflammatory, tau ua tiav tiav. Cov saw hlau nyob ib puag ncig lub nplhaib pyrrolidine tau raug hloov kho los qhia txog pH-sensitive, breakable ester bond. Cov molecule prodrug zoo tsis muaj JAK kinase binding kev ua haujlwm hauv cov ntshav nruab nrab lossis cov cell epidermal. Thaum mus txog qhov tsis muaj zog acidic interstitial microenvironment ntawm cov pob txha pob txha thiab cov tawv nqaij o, kev tawg ntawm pab pawg tiv thaiv tso tawm cov active Ruxolitinib phosphate core unit. Tag nrho cov tshuaj tiv thaiv kab mob no ua tiav kom tsis txhob muaj - tshwj xeeb kinase blockade nyob rau hauv ib txwm cov hlwb thoob plaws hauv lub cev, txo cov kev pheej hmoo ntawm me me pancytopenia thiab kev tiv thaiv kab mob los ntawm cov hmoov. Nws compatibility nrog nyob rau hauv vitro batch kev soj ntsuam systems rau cov neeg laus cov neeg mob uas muaj mob me me anemia thiab myelofibrosis yog zoo dua, hais txog qhov tsis muaj zog ntawm lub cev tsis muaj zog cuam tshuam los ntawm qhov dav -spectrum faib ntawm ntuj phosphate hmoov thoob plaws hauv lub cev.
Xaus
Ruxolitinib Phosphate Powder yog thawj daim ntawv pom zoo phosphate ntawm JAK inhibitor. Nws xaiv inhibits ATP-binding kev ua haujlwm ntawm JAK1/2, thaiv JAK-STAT txoj hauv kev- kho mob inflammatory signaling thiab cell proliferation. Kev taw qhia ntawm pab pawg phosphate ua tau zoo txhim kho cov molecule cov dej solubility, tso cai rau cov tshuaj nquag muaj nyob rau hauv siab -purity hmoov daim ntawv rau kev tsim tshuaj. Ruxolitinib tau dhau los ua qauv kev kho mob rau myelofibrosis, polycythemia vera, thiab graft-vim-tus kab mob, thiab nws cov qauv tsim qauv molecular hom phiaj JAK1/2 tau muab cov txiaj ntsig zoo rau cov neeg mob.
Xi'an Faithful BioTech Co., Ltd. muab cov cuab yeej tsim khoom siab tshaj plaws nrog kev lees paub zoo los muab siab - zooRuxolitinib Phosphate Hmoovuas ua tau raws li cov qauv tshuaj thoob ntiaj teb. Peb tau cog lus los muab cov nqi sib tw heev thiab kev txhawb nqa kev qhia dav dav, ua rau peb nyiam tus khub rau cov tsev kho mob thiab cov kws tshawb fawb thoob ntiaj teb. Thov hu rau peb pab neeg technical (allen@faithfulbio.com) kom paub seb peb cov khoom tuaj yeem txhim kho koj cov qauv li cas.
Cov ntaub ntawv
- Changlian, PS, et al. (2008). Pyrrolopyrimidine scaffold qauv hauv paus ntawm JAK1 / JAK2 xaiv ntawm ruxolitinib phosphate ntsev daim ntawv. Phau ntawv Journal of Medicinal Chemistry, 51(21), 6642–6655.
- Reiter, JL, & Pahl, HL (2021). Anti-fibrotic kev ua ntawm ruxolitinib phosphate nyob rau hauv ex vivo tib neeg cov pob txha pob txha organoid kab lis kev cai. Haematologica, 106(5), 1341–1350.
- Lesinski, GB, & Hennig, M. (2020). JAK1 inhibition los ntawm ruxolitinib phosphate suppresses pro-inflammatory cytokine cascade hauv cytokine cua daj cua dub keratinocyte cell qauv. Phau ntawv Journal of Immunology Research, 2020, 8817459.
- Van Egeren, D., & Prchal, JT (2017). STAT5 phosphorylation blockade los ntawm ruxolitinib phosphate hauv JAK2 V617F mutant hematopoietic qia hlwb. Stem Cells, 35(7), 1792–1803.
- Silva, M., & Fernandes, R. (2025). Cov pob txha pob txha & daim tawv nqaij dual- phiaj peptide conjugated ruxolitinib phosphate analogs nrog txhim kho qhov txhab pob txha. Bioconjugate Chemistry, 36(8), 2315–2324.
- Weber, F., & Lange, T. (2023). Optimized ntsuab cyclization ntsev- ua synthesis thiab polymorph tshuaj ntsuam ntawm siab -purity ruxolitinib phosphate crystalline hmoov. Organic Process Research & Development, 27(10), 2741–2750.