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阿拉丁小分子抑制剂、激动剂、拮抗剂--Stem Cell 信号通路

2020-09-21

Stell Cell

      不同器官内的组织维持都需要干细胞,干细胞的活性通常是由外部的微环境(生态位)决定的。因此为了满足体内平衡或再生的需要,需要精准地控制干细胞的输出。一些关键的信号通路已被证明在这种调节能力中发挥重要作用,包括Wnt、Hedgehog、Hippo、Notch、BMP/TGF-β等信号转导途径都已被实验证实可调控各类干细胞的特性,比如:细胞自我更新、细胞生存、增殖和分化等。

Stem Cell信号通路转导过程

#Wnt信号通路

      Wnt通路参与基因表达、细胞行为、细胞粘附和细胞极性的调控,以及促进多能性。Wnt信号通路至少有三个分支:1)Catenin通路(经典的Wnt通途径路);2)平面细胞极性通路;3)Wnt/Ca2+。后两种可分为非经典Wnt通路。

      经典Wnt信号通路中,Wnt蛋白通过结合到各自的二聚体细胞表面受体(7个Frizzled蛋白和LRP5/6),Dvl蛋白被激活,诱导GSK从Axin上解离,进而可调控许多基因转录的β-catenin降解被抑制。

      在平面细胞极性通路中,Frizzled蛋白激活JNK,导致上皮平面细胞的不对称细胞骨架组织和极化协调,该途径涉及Fmi、Knyand Stbm。Wnt/Ca2+途径导致细胞内Ca2+释放。该途径涉及PLC和PKC的激活。Ca2+升高可激活磷酸酶钙调磷酸酶,导致转录因子NFAT去磷酸化并在细胞核中积累。

#Hedgehog信号通路

      在哺乳动物发育过程中尤其是神经管和骨骼具有高活性,一些出生后的器官,如中枢神经系统和肺,也依赖继续的Hh信号传导来进行损伤后组织体内的修复和平衡。

      Hedgehog信号通路中,Hh(SHh、IHh、DHh)的同源物在细胞表面上结合Ptch,并使其从初级纤维中移除。Smoothened被去除并移动到主要纤毛,激活Gli转录因子。在此过程中,Gli转录因子被加工成活化剂并转移到细胞核中以诱导Hh靶基因的转录。Gli1作为转录激活因子,Gli3作为抑制因子,Gli2可根据转录后和翻译后修饰来激活或抑制基因表达。

#Hippo信号通路

      哺乳动物的Hippo信号通路中,上游的膜蛋白受体受胞外的生长抑制信号刺激后,经过一系列激酶复合物的磷酸化级联反应,最终将磷酸化下游的转录激活因子(YAP和TAZ)。磷酸化的转录激活因子与细胞骨架蛋白相互作用,被滞留在胞质内,不能进入细胞核行使其转录激活功能,从而实现对器官大小和体积的调控。此外,近年来的研究证实Hippo信号传导通路还在癌症发生、组织再生以及干细胞的功能调控上发挥重要的作用。

#Notch信号通路

      Notch信号通路是一个存在于大多数多细胞生物中高度保守的细胞信号途径。Notch信号在胚胎和成人发育过程中的增殖、干细胞维持和分化等细胞基本过程的调控中起着关键作用。Notch受体是大型单通道I型跨膜蛋白。在特定配体结合后,Notch受体的胞内部分被分离并转移到细胞核,在那里与转录因子结合。

      Notch信号在许多癌症中是不正常的,缺陷的Notch信号在许多疾病中都有牵连,包括CADASIL(常染色体显性遗传性脑动脉病伴皮层下梗死和白质脑病)、T-ALL (T细胞急性淋巴细胞白血病)、Alagille综合征、多发性硬化症和其他各种疾病状态。

#BMP/TGF-β、FGF信号通路

       在人类胚胎干细胞中,BMP/TGF-β信号通路和FGF信号通路负责维持胚胎干细胞的多能性和自我更新。BMP/TGF-β信号通路通过Smad蛋白传导信号,FGF信号通路则激活MAPK和Akt通路。BMP/TGF-β信号通路和FGF信号通路、以及Wnt信号通路导致一些转录因子激活和表达。这些转录因子促进胚胎干细胞特异性基因的表达,调节自身的表达,并作为多能性的有用标志物。

Stem Cell信号通路图

产品列表

*Beta Amyloid

项目号产品名称规格CAS包装细胞靶点IC50EC50
D126677DAPT≥98%208255-80-55mg,10mg,25mg,50mgHEK 293细胞γ-secretase20 nM
R127403RO4929097≥99%847925-91-15mg,10mg,50mg无细胞γ secretase4 nM
Aβ40
14 nM
Notch
5 nM
M126008MK-0752≥99%471905-41-65mg,10mg,50mg
γ-secretase5 nM
B126453Avagacestat (BMS-708163)≥99%1146699-66-25mg,10mg,50mg
Aβ400.3 nM
Aβ420.27 nM
L128069LY2811376≥99%1194044-20-65mg,10mg,50mg
BACE1
239 nM-249 nM

300 nM
H1088132-羟丙基-β-环糊精97%128446-35-55g,25g,100g,250g
amyloid-β aggregation

 

*5-HT Receptor

项目号产品名称规格CAS包装细胞靶点IC50KiED50pKi
F131623Fluoxetine HCl≥98%(HPLC)56296-78-71g,5g,25g
5-HT



V129637Venlafaxine hydrochloride≥98% (HPLC)99300-78-41g,5g,25g,100g
5-HT



D129639Dapoxetine hydrochloride≥98% (HPLC)129938-20-1250mg,1g,5g
5-HT



I251279Iloperidone≥98%133454-47-450mg,250mg,1g,5g
5-HT



V129787Vortioxetine (Lu AA21004) HBr≥98%960203-27-45mg,25mg,100mg
5-HT1A15 nM


5-HT1B33 nM


5-HT3A3.7 nM


5-HT719 nM


SERT1.6 nM


F129671Fluvoxamine maleate≥98%61718-82-9250mg,1g,5g,25g,100g
5-HT



S129789Sertraline HCl≥98% (HPLC)79559-97-01g,5g
5-HT
13 nM

L129555Lamotrigine≥98%84057-84-11g,5g人类血小板5-HT240 μM


大鼠脑突触体5-HT474 μM


C129687Clomipramine HCl≥99%17321-77-61g,5g,25g
SERT0.14 nM


NET54 nM


DAT3 nM


E122736草酸右旋西酞普兰98%219861-08-250mg,250mg,1g,5g
5-HT
0.89 nM

D123291盐酸度洛西汀≥98.0%(HPLC)136434-34-91g,5g,25g
5-HT
4.6 nM

M129386Milnacipran hydrochloride≥99%101152-94-710mg,50mg,250mg,500mg,1g,5g,25g
NET77 nM


SERT220 nM


A129730盐酸阿米替林≥98%549-18-81g,5g,25g,100g
5-羟色胺受体3.45 nM


去甲肾上腺素受体13.3 nM


5-HT47.31 nM


5-HT2235 nM


sigma 1受体287 nM


L174987Levomilnacipran hydrochloride97%175131-60-9100mg,250mg,1g





D1542623-(3,4-二羟基苯基)-2-甲基-L-丙氨酸倍半水合物>98.0%(HPLC)(T)555-30-65g,25g,100g
DOPA decarboxylase

21.8 mg/kg
C122737氢溴酸西酞98%59729-32-71g,5g
serotonin reuptake1.8 nM


V129637Venlafaxine hydrochloride≥98% (HPLC)93413-69-51g,5g,25g,100g
SNRI



D136408盐酸去甲咪嗪≥98%58-28-61g,5g,25g





T129695曲唑酮 盐酸盐98%25332-39-21g
5-HT



P137447Protriptyline Hydrochloride≥98%1225-55-425mg,100mg





A129721Atomoxetine HCl≥98%82248-59-750mg,250mg,1g
Norepinephrine (NE) transporter
5 nM

C126883氯氮平≥98%(GC)5786-21-0100mg,1g,5g,25g,100g
5-HT110 nM


O126519Olanzapine≥99%132539-06-11g,5g
5-HT2



D2 receptor



K129651Ketanserin≥97%74050-98-950mg,250mg,1g
5-HT2A
2.5 nM

5-HT2C (Rat)
50 nM

5-HT2C (Human)
100 nM

L129669Latrepirdine≥96%97657-92-65mg,10mg,50mg
GluR



Histamine receptor 



5-HT



A129730盐酸阿米替林≥98%50-48-61g,5g,25g,100g





A124691阿戈美拉汀≥98%(HPLC)138112-76-25mg,25mg,50mg,250mg,1g,5g,25g
5-HT2C 



A124739Asenapine maleate≥98% (HPLC)85650-56-210mg,50mg,250mg,1g





R127644Risperidone≥98%106266-06-2500mg,5g,25g,100g
5-HT2A
0.17 nM

α2c-adrenergic receptor 
1.3 nM

D2 receptor
3.57 nM

D3 receptor
3.6 nM

D2L Receptor
4.16 nM

E129717Ziprasidone HCl≥98%122883-93-6250mg,1g
5-HT receptor



Dopamine receptor



W129689WAY-100635 Maleate≥99%1092679-51-05mg,25mg,100mg
5-HT0.95 nM


B129706Blonanserin≥98% (HPLC)132810-10-725mg,100mg
5-HT2
3.98 nM

dopamine D2 receptor
14.8 nM

S125056SB269970 HCl-261901-57-910mg
5-HT7



S129658SB269970 HCl≥99%261901-57-910mg,50mg
5-HT7



G120176盐酸格拉司琼98%107007-99-810mg,50mg,1g,5g
5-HT3



M129297Mirtazapine≥98%85650-52-8100mg,1g
5-HT



S127746SB742457≥97%607742-69-85mg,25mg
5-HT6



B129690BRL-15572≥99%193611-72-25mg,10mg,50mg
5-HT1D


7.9
5-HT1A


7.7
5-HT2B


7.4
5-HT2A


6.6
5-HT7


6.3
P129785PRX-08066 Maleic acid≥99%866206-55-55mg,10mg,50mg
5-HT2B3.4 nM


T124762盐酸托烷司琼≥98.0%105826-92-4250mg,1g,5g
5-HT3



P129438Pizotifen Malate≥99%5189-11-7100mg,500mg





A129701Azasetron HCl≥99%123040-16-425mg,100mg
5-HT30.33 nM


F129636夫洛丙酮≥99%2295-58-150mg
5-HT1A



O129694Ondansetron≥99%99614-02-510mg,50mg,250mg
5-HT3



P129744Palonosetron HCl≥99%135729-62-3100mg,500mg
5-HT3



V129763VUF 10166≥99%155584-74-010mg,50mg,250mg
5-HT3A
0.04 nM

5-HT3AB
22 nM

N159830奈法唑酮盐酸盐99%82752-99-6200mg,1g





C101491盐酸赛庚啶98%41354-29-41g,5g,25g
5-HT20.6 nM


SETD7/91 μM


O129679Ondansetron Hydrochloride Dihydrate≥98% (HPLC)103639-04-91g,5g
5-HT3 receptor 
6.16 nM

A135530Alosetron Hydrochloride≥98% (HPLC)122852-69-11g,5g
5-HT3 receptor 



S132232Sarpogrelate Hydrochloride≥98%135159-51-25mg,25mg,100mg
5-HT2A


8.52
5-HT2B


6.57
5-HT2C


7.43
R166990Ramosetron hydrochloride98% (HPLC)132907-72-310mg,50mg,100mg,250mg
5-HT3 receptor
0.091 nM

P111269葛根素分析标准品,≥98%3681-99-020mg
5-HT2C



P111270葛根素98%3681-99-01g,5g,25g,100g
5-HT2C



T124762盐酸托烷司琼≥98.0%89565-68-4250mg,1g,5g
5-HT3 receptor 
5.3 nM

α7 nAChR
6.9 nM

C134704Cyclobenzaprine hydrochloride98%6202-23-91g,5g,25g
5-HT2 receptor



G127257Granisetron-109889-09-025mg,50mg,100mg,250mg
5HT-3



L129692LY310762≥95%192927-92-710mg,50mg
5-HT1D
249 nM

P125293Palonosetron-135729-61-210mg,100mg
5-HT3 receptor
0.17 nM

M1245745-甲氧基色胺97%608-07-1250mg,1g,5g,25g
5-HT1



5-HT2



5-HT4



5-HT6



5-HT7



T162853Tianeptine sodium salt hydrate>98.0%(HPLC)30123-17-2200mg,1g,5g
5-HT



S129681Sumatriptan Succinate≥98% (HPLC)103628-48-450mg,100mg,250mg,1g
5-HT



P129662Prucalopride≥99%179474-81-810mg,50mg
5-HT4A
2.5 nM

5-HT4B
8 nM

A124880Aripiprazole≥99%129722-12-91g,5g
5-HT1A
4.2 nM

N129630Naratriptan hydrochloride≥98%143388-64-110mg,25mg,50mg,100mg
5-HT



R129638Rizatriptan Benzoate≥98%(HPLC)145202-66-010mg,50mg,250mg,1g,5g
5-HT1



Z129649Zolmitriptan≥98%(HPLC)139264-17-8200mg,250mg
5-HT



M129673Mosapride Citrate≥98%112885-42-410mg,50mg,250mg,1g,5g,25g
5-HT4 



E129729Eletriptan HBr≥98%177834-92-310mg,50mg,250mg,1g,5g
SSRI 



5-HT1A 



A129703Almotriptan Malate≥99%181183-52-81g
5-HT1B



5-HT1D



T168187Tegaserod maleate98% (HPLC)189188-57-610mg,50mg
5-HT4 receptor



B129734BRL-54443≥98%57477-39-110mg,50mg,100mg
5-HT1A


7.2
5-HT1B 


6.9
5-HT1D


7.2
5-HT1E


8.7
5-HT1F


9.25
B178171brexpiprazole97%913611-97-91g
5-HT1A
0.12 nM

D2L
0.3 nM

5-HT1A
0.12 nM

5-HT2A
0.47 nM

α1B受体
0.17 nM

α2C受体
0.59 nM

M179481Mosapride95%112885-41-31g,5g
5HT4



S111161血清胺盐酸盐AR153-98-01g,5g,25g
5-HT



V124992Vilazodone≥98%163521-12-810mg,50mg





F167802Flibanserin98% (HPLC)167933-07-55mg,25mg
5-HT1A
1 nM

5-HT2A
49 nM

D4 receptor
4-24 nM

V125545Vortioxetine≥98%508233-74-710mg,50mg,250mg,1g





P129402Azacyclonol≥99%115-46-850mg





*Gamma-secretase

项目号产品名称规格CAS包装细胞靶点IC50
D126677DAPT≥98%208255-80-55mg,10mg,25mg,50mgHEK 293细胞γ secretase(Aβ)20 nM
R127403RO4929097≥99%847925-91-15mg,10mg,50mg无细胞γ secretase4 nM
Aβ4014 nM
Notch5 nM
S125519Semagacestat (LY450139)≥98%425386-60-35mg,10mg,50mg人神经胶质瘤细胞Aβ4210.9 nM
Aβ4012.1 nM
Aβ3812.0 nM
Notch14.1 nM
M126008MK-0752≥99%471905-41-65mg,10mg,50mg
Aβ405 nM
B126453Avagacestat (BMS-708163)≥99%1146699-66-25mg,10mg,50mg
Aβ400.3 nM
Aβ420.27 nM
Y129283YO-01027≥97%209984-56-52mg,5mg,25mg无细胞APPL2.6 nM
Notch2.9 nM
L125846LY-411575≥98%209984-57-65mg,25mg,100mgHEK293细胞APP0.078 nM
NΔE0.082 nM
Notch0.39 nM
P127448PF-3084014≥98%1290543-63-35mg,10mg,25mg,50mg,100mg无细胞γ-secretase 6.2 nM

*GluR

 

项目号产品名称规格CAS包装细胞靶点IC50EC50Ki
C129279Celecoxib≥99%169590-42-5100mg,1g,5g,25g,100gSf9细胞COX-240 nM

N127367Nepafenac≥99%78281-72-8250mg,1g,5g
COX1


COX2


I129291Ibuprofen≥98%(GC)15687-27-15g,25g,100g,250g,500g
COX-113 μM

COX-2370 μM

I106885吲哚美辛99%53-86-15g,25g,100g,500g
COX10.28 μM

COX214 μM

S125148Sulindac≥98%38194-50-21g,5g,25g,100g
COX


D155733Diclofenac>98.0%15307-86-51g,5g,25g,100g
COX-1


COX-2


R126597Rofecoxib≥98%162011-90-750mg,250mg
COX-218 nM

M129228Meloxicam≥98%71125-38-75g,10g,25g,100g




D129705地塞米松磷酸钠≥99%55203-24-250mg,250mg
IL receptor


B129286Bufexamac≥98.0%(HPLC)2438-72-45g,25g
IFN-α
8.9 μM
A104180乙酰水杨酸99% 50-78-225g,100g,500g,2.5kg
COX1


COX2


A118582乙酰水杨酸用于植物细胞培养, ≥99.0% 50-78-2250g
COX1


COX2


S129974Suprofen≥99%40828-46-410mg,50mg
COX-1


COX-2


P129294Piroxicam≥98%(HPLC)36322-90-41g,5g,25g,100g
COX


E129317Etodolac≥98%41340-25-41g,5g,25g,100g
COX


K129331Ketoprofen≥98%(HPLC)22071-15-45g,25g,100g,250g,500g
COX-1


COX-2


D129332Diclofenac Sodium≥99%15307-79-65g,25g,100g,500g
COX-160 nM

COX-2200 nM

I129329Ibuprofen Lysine≥99%57469-77-920mg,100mg
COX


L129341Lornoxicam≥98% (HPLC)70374-39-9250mg,1g,5g
COX-15 nM

COX-28 nM

K194835酮咯酸98%74103-06-3250mg,1g,5g
COX-11.23 μM

COX-23.50 μM

N129290Naproxen Sodium≥98%26159-34-25g,25g,100g
COX-18.7 μM

COX-25.2 μM

L129349Lumiracoxib≥98%220991-20-850mg,250mg
COX-1

3 μM
COX-2

60 nM
P129299Pranoprofen≥99%52549-17-41g,5g
COX


Z129346Zaltoprofen≥98%74711-43-6250mg,1g,5g,25g,100g
COX-1


COX-2


A129429Acemetacin≥98%53164-05-91g,5g,25g
COX


T129337托灭酸≥98%13710-19-55g,25g,100g
COX-20.2 μM

V125795Valdecoxib≥99%181695-72-710mg,50mg,1g,5g
COX-25nM

P109420非那西汀≥98.0% (HPLC) 62-44-225g,100g,500g
COX


N159746Nimesulide>98.0%(HPLC)51803-78-21g,5g,25g
COX-226 μM

A129507Amfenac Sodium Monohydrate≥99%61618-27-750mg,250mg,1g,5g,25g
COX-1250 nM

COX-2150 nM

N129597尼氟酸>98.0%(HPLC)4394-00-71g,5g,25g,100g
COX-2


A110659安替比林CP,98%60-80-0100g,500g
COX3


A110660安替比林99%60-80-0100g,500g
COX3


A129352Ampiroxicam≥98%99464-64-950mg,250mg,1g
COX


S161049Naproxen>99.0%22204-53-15g,25g,100g,500g
COX-1


COX-2


B107666次水杨酸铋97%14882-18-9100g,500g
COX120 nM

COX220 nM

X139028(±)-磺吡酮≥96%57-96-51g,5g




C153919Carprofen>98.0%(HPLC)53716-49-71g,5g,25g,100g
canine COX230 nM

D129411Diclofenac Diethylamine≥99%78213-16-85g,25g
COX1


COX2


D133115二氟苯水杨酸≥98%22494-42-41g,5g
COX


P113217菲尼酮98.50%92-43-325g,100g,500g
COX


LOX


P113218菲尼酮97%92-43-3100g,500g
COX


LOX


M157895甲芬那酸>98.0%61-68-725g,100g,500g
COX-1


COX-2


E126660Etoricoxib≥98.0%202409-33-410mg,50mg,250mg,1g,5g
COX-2


S161351D-α-生育酚>97.0%(GC)59-02-9 25g,100g,500g




O129611Oxaprozin≥98%21256-18-85g,25g,100g
COX-1


COX-2


R107337吴茱萸次碱分析标准品,≥98%84-26-410mg,20mg
COX2


R107338吴茱萸次碱98%84-26-450mg,250mg,1g
COX2


S104922D(-)-水杨苷99%138-52-35g,25g,100g
COX1 


S104923D(-)-水杨苷分析标准品,≥99%138-52-320mg
COX1 


S118533水杨酸用于植物细胞培养,≥99 %69-72-7500g




S104158水杨酸AR,99.5%69-72-7250g,1kg,2.5kg




S104162水杨酸ACS,≥99.0%69-72-7250g,1kg




X139169黄腐酚≥97.0%(HPLC)6754-58-15mg,25mg,100mg




F121952Flunixin meglumine98%42461-84-7250mg,1g,5g,25g




*GluR

项目号产品名称规格CAS包装细胞靶点IC50KiEC50
X113958黄尿酸96%59-00-71g,5g
mGlu2


R129533Riluzole≥98%1744-22-51g,5g,25g,100g
mGlu3 


L129669Latrepirdine≥96%97657-92-65mg,10mg,50mg
histamine receptors

GluR


5-HT receptors

C126237CTEP (RO4956371)≥99%871362-31-15mg,10mg,50mg
mGlu52.2 nM

M127959MPEP≥98%96206-92-7 10mg,50mg,250mg
mGluR536 nM

L127760LY404039≥99%635318-11-55mg,25mg,50mg
mGlu2/mGlu3149 nM
mGlu2/mGlu392 nM
G103978L-谷氨酸99%56-86-0100g,250g,500g,2.5kg




G103979L-谷氨酸超纯级,≥99.5% (NT)56-86-0100g,500g,2.5kg




G107510L-谷氨酸非动物源,EP,JP,USP ;用于细胞培养,98.5 to 101.0%56-86-0100g,500g




A129508ADX-47273≥99%851881-60-25mg,10mg,50mg
mGlu5

0.17 μM
V129515VU 0357121≥98%433967-28-310mg,50mg,250mg
mGluR5

30 nM
S161191L-O-磷酸丝氨酸>98.0%(T)407-41-01g,5g,25g
mGluR


V129525VU 0364770≥98%61350-00-310mg,50mg,250mg
mGlu4

1.1 μM
V129527VU 0361737≥98%(HPLC)1161205-04-410mg,50mg,250mg人类受体mGluR4

240 nM
大鼠受体mGluR4

110 nM
D107632D-谷氨酰胺98%5959-95-51g,5g,25g,100g





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