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阿拉丁小分子抑制剂、激动剂、拮抗剂--自噬信号通路

2020-06-23

自噬

自噬是一个吞噬自身细胞质蛋白或细胞器并使其包被进入囊泡,并与溶酶体融合形成自噬溶酶体,降解其所包裹的内容物的过程。在哺乳动物细胞中,自噬主要有三种类型:微自噬、巨自噬和分子伴侣介导的自噬(CMA)。微自噬通过溶酶体的膜直接包裹待降解物质等,并在溶酶体内降解。巨自噬则由双层膜囊泡包裹待降解物质然后运送到溶酶体中降解。而在分子伴侣介导的自噬(CMA)过程中,分子伴侣识别待降解蛋白,去折叠后并转移目的蛋白至溶酶体内。

自噬通常发生在营养缺乏的情况下,也与发育、分化、神经退行性疾病、应激、感染和癌症等生理和病理过程有关。自噬机制的受损与肿瘤、神经退行性疾病、代谢相关疾病、免疫性疾病等发病过程密切相关。

自噬信号通路转导过程

巨自噬:(1)起始:UKL和Beclin 1蛋白复合物起始自噬泡的形成。(2)延伸:Atg5-Atg12-Atg16L复合物形成并与自噬泡融合;微管相关蛋白轻链3(LC3)由可溶解形式(LC3-I)转变为脂溶形式(LC3-II),与自噬泡结合形成自噬体。(3)融合与降解:自噬体捕获需降解或清除的蛋白质、细胞器等物质;自噬体与溶酶体融合形成自噬溶酶体,释放内容物降解,完成自噬。

线粒体自噬:属于选择性自噬,主要是降解细胞中损伤和不需要的线粒体。线粒体处于健康状态时,PINK 蛋白通过PARL的促进持续降解,而当线粒体功能障碍时, PINK蛋白会处于稳定状态,从细胞质中招募E3泛素连接酶Parkin,来诱导线粒体自噬。Parkin会诱导线粒体膜蛋白的聚泛素化,由此导致通过LC3-作用区域(LIR)与LC3结合的自噬受体蛋白的SQSTM1/p62,NBR1和Ambra1聚集。另外,在特定细胞中,BNIP3 和 BNIP3L/NIX(也存在LIR)可通过非泛素反应机制聚集自噬的相关因子,从而促进自噬体的形成。

自噬信号通路图

产品列表

按靶点分类:     

*Autophagy

项目号产品名称规格CAS包装细胞靶点IC50EC50KikdED50
L124970LY294002≥98%154447-36-610mg,25mg,50mg无细胞p110α0.5 μM



p110δ0.57 μM



p110β0.97 μM




DNA-PK1.4 μM



P106869紫杉醇99%33069-62-410mg,50mg,250mg,1g,5g人内皮细胞Microtubule0.1 pM



P106868紫杉醇分析标准品,≥99%33069-62-410mg人内皮细胞Microtubule0.1 pM



W100984Wortmannin98%19545-26-75mg,10mg,25mg无细胞PI3K3 nM



DNA-PK16 nM



ATM150 nM



MLCK170 nM



M1294963-甲基腺嘌呤98%5142-23-450mg,250mg,1g,5g,25gHeLa细胞Vps3425 μM



PI3Kγ60 μM



N129755Nocodazole≥99%31430-18-910mg,50mg
Abl0.21 μM



Abl(E255K)0.53 μM



Abl(T315I)0.64 μM



C129284磷酸氯喹≥99%50-63-55g,10g,25g,100g,500gATM




A134451Azithromycin分析标准品83905-01-525mg






P170364PFK1598% (HPLC)4382-63-25mg,25mg
PFKFB3207 nM



S166799Spautin-198% (HPLC)1262888-28-75mg,25mg
USP100.5779 μM



USP130.6916 μM



S105956青藤碱盐酸盐97%6080-33-71g,5g






S101688青藤碱盐酸盐分析标准品,≥97%6080-33-720mg






H141480硫酸羟基氯喹≥98%747-36-4250mg,1g,5g,25g
TLR9




V125336Vorinostat≥99.0%149647-78-9100mg,500mg,1g,5g






A127419ABT-737≥97%852808-04-95mg,25mg,100mg无细胞Bcl-xL
78.7 nM


Bcl-2
30.3 nM


Bcl-w
197.8 nM


Y129399Y-27632 dihydrochloride≥98%129830-38-25mg,10mg,50mg,100mg
ROCK1

140 nM

ROCK2

300 nM

S293790Rapamycin≥95%(HPLC)53123-88-950mg,250mg,1gHEK293细胞mTOR~0.1 nM



S115842Rapamycin≥98%(HPLC)53123-88-910mg,25mg,50mg,250mg,1gHEK293细胞mTOR~0.1 nM



E129310Erlotinib HCl (OSI-744)≥99%183319-69-9100mg,500mg,1g,5g无细胞EGFR2 nM



O127383Obatoclax Mesylate≥97%803712-79-05mg,10mg,50mg,100mg无细胞Bcl-2

0.22 μM

P125961PI-103≥98%371935-74-910mg,50mg,100mg无细胞p110α2 nM



p110β3 nM



p110δ3 nM



p110γ15 nM



mTOR/DNA-PK30 nM



mTOR/DNA-PK23 nM



G120180盐酸吉西他滨98%122111-03-910mg,50mg,250mg,1g,5g,25gPANC1细胞DNA合成50 nM



MIAPaCa2细胞40 nM



BxPC3细胞18 nM



Capan2细胞12 nM



P129635PP242≥98%1092351-67-15mg,10mg,50mg无细胞mTOR8 nM



DNA-PK0.41 μM



T127425Temozolomide≥98% (HPLC)85622-93-1250mg,500mg,1g,5g25g,100g






M107827Metformin hydrochloride97%1115-70-45g,25g,100g,500g






F122336Fasudil Hydrochloride98%105628-07-7100mg,250mg,500mg,1g,5g
ROCK2

0.33 μM

PKA

1.6 μM

PKG

1.6 μM

PKC

3.3 μM

MLCK

36 μM

T101373他莫昔芬柠檬酸盐99%54965-24-11g,5g,25g
ER




T129642Torin 1≥97%1222998-36-810mg,25mg,50mg无细胞mTORC12 nM



mTORC210 nM



R107315白藜芦醇99%501-36-01g,5g,25g,100g
COX1.1 μM



LOC2.7 μM



R107314白藜芦醇分析标准品501-36-0100mg
COX1.1 μM



LOC2.7 μM



D137736Dexamethasone98%50-02-21g,5g,25g






G127944Gemcitabine≥99%95058-81-450mg,100mg,250mg,1g,5g,25g






B102375布雷非德菌素 A≥98% (HPLC)20350-15-65mg,25mgHCT 116ATPase0.2 μM



G102383格尔德霉素≥98% (HPLC)30562-34-610mg,50mg,250mgSKBr3p18570 nM



无细胞HSP90


1.2 μM
P129961Pifithrin-α (PFTα)≥97%63208-82-210mg,50mg
p53




N130841氯硝柳胺98%50-65-750g,250g无细胞STAT30.7 μM



N114456氯硝柳胺分析标准品50-65-7100mg无细胞STAT30.7 μM



O118724奥美拉唑98%73590-58-61g,5g,25g,100g






A129574Amiodarone hydrochloride≥98%19774-82-41g,5g,25g,100g






L129465Loperamide HCl≥98%34552-83-55g,25g
μ阿片受体

3.3 nM

δ阿片受体

48 nM

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






D129539卡马西平≥98.0%298-46-45g,25g,100g
钠离子通道131 μM



C102161盐酸可乐定98%4205-91-8250mg,1g,5g,100g
α2肾上腺素能受体



0.02±0.01 mg/kg
F129912Flubendazole≥98%(HPLC)31430-15-65g,25g,100g






N129506Nimodipine≥98%66085-59-4250mg,1g,5g






D102176乙酸地塞米松98%1177-87-3250mg,1g,5g,25g






N123276尼群地平≥95.0%39562-70-425mg,100mg,500mg,1g
钙离子通道95 nM



S114285磺胺乙酰钠分析标准品127-56-0250mg,25g






I102722异钩藤碱分析标准品,≥98%6859-01-410mg,20mg






T137974他莫西芬≥99%10540-29-11g,5g,25g






T137975他莫西芬分析标准品,≥99.0% (HPLC)10540-29-150mg






V107236Vincristine sulfate98%2068-78-225mg,100mg
微管32 μM



V107235硫酸长春新碱分析标准品,>99%2068-78-210mg
微管32 μM



S1610232-丙戊酸钠≥98.0%1069-66-55g,25g,100g,500g
HDAC




S129300STF-62247≥98%315702-99-95mg,25mg,100mg






S171217Sulfacetamide sodium salt monohydrate-6209-17-2100g,500g
DHPS9.5 μM



M126521MG-132≥98%133407-82-65mg,25mg,100mg,1g
蛋白酶体100 nM



C153919Carprofen>98.0%(HPLC)53716-49-71g,5g,25g,100g
COX-23.9 μM



COX-122.3 μM



FAAH78.6 μM



H123383肝素钠≥180 USP units/mg9041-08-1100KU,250KU,500KU,1000KU






H104201肝素钠185 USP units/mg9041-08-11g,5g,25g






O126162Olaparib (AZD2281, Ku-0059436)≥98%763113-22-010mg,25mg,100mg,250mg,1g
PARP-15 nM



PARP-21 nM



D107159盐酸阿霉素98%25316-40-925mg,100mg,250mg,500mg,1g,5g






T125887TAK-242≥98%243984-11-45mg,10mg,50mg,100mg
NO1.8 nM



TNF-R1.9 nM



IL-61.3 nM



A124869ABT-199 (GDC-0199)≥99%1257044-40-810mg,50mg
Bcl-2

<0.01 nM

B101389巴佛洛霉素A1≥95.0 %88899-55-21mg,5mg
V-ATPase




H123383肝素钠≥180 USP units/mg9041-08-1100KU,250KU,500KU,1000KU






H104201肝素钠185 USP units/mg9041-08-11g,5g,25g






O126162Olaparib (AZD2281, Ku-0059436)≥98%763113-22-010mg,25mg,100mg,250mg,1g
PARP-15 nM



PARP-21 nM



D107159盐酸阿霉素98%25316-40-925mg,100mg,250mg,500mg,1g,5g






T125887TAK-242≥98%243984-11-45mg,10mg,50mg,100mg
NO1.8 nM



TNF-R1.9 nM



IL-61.3 nM



A124869ABT-199 (GDC-0199)≥99%1257044-40-810mg,50mg
Bcl-2

<0.01 nM

B101389巴佛洛霉素A1≥95.0 %88899-55-21mg,5mg
V-ATPase




J166817(+)-JQ198% (HPLC)1268524-70-45mg,25mg
BRD4177 nM



BRD4233 nM



S131899SB-203580≥98%(HPLC)152121-47-65mg,25mg,100mg,500mg
SAPK2a/p3850 nM



SAPK2b/p38β2500 nM



S125267SP600125≥98%129-56-625mg,100mg,500mg,1g,5g
JNK140 nM



JNK240 nM



JNK390 nM



C129710CHIR-99021 (CT99021) HCl≥98%252917-06-95mg,25mg,100mg
GSK-3α10 nM



GSK-3β6.7 nM



C125082CHIR-99021≥98%252917-06-95mg,25mg
GSK-3α10 nM



GSK-3β6.7 nM



E127109Enzalutamide≥98%915087-33-125mg,100mg,250mg,1g,5gLNCaP前列腺细胞AR36 nM



S125098Sorafenib≥99%284461-73-0250mg,1g
Raf-16 nM



B-Raf20 nM



VEGFR-322 nM



U127670U0126-EtOH≥97%1173097-76-125mg,100mg,500mg
MEK170 nM



MEK260 nM



M129684MK-2206 2HCl≥98%1032350-13-210mg,50mg,100mg
Akt15 nM



Akt212 nM



Akt365 nM



T127461Trametinib (GSK1120212)≥98%871700-17-310mg,50mg,100mg,250mg,500mg,1g
MEK12 nM



MEK22 nM



P126620PD98059≥98%167869-21-810mg,50mg
MEK12-7 μM



MEK250 μM



F127328Forskolin≥98%66575-29-910mg,50mg,100mg,500mg,1g
腺苷酸环化酶41 nM0.5 μM


B125789Bortezomib (PS-341)≥98%179324-69-75mg,25mg,100mg,1g
20S 蛋白酶体

0.6 nM

O124003奥沙利铂99%61825-94-325mg,100mg,500mg人黑色素瘤细胞系 C320.98 μM



G3610.14 μM



B129693BAY 11-7082≥98%19542-67-750mg,250mg,1g
USP70.19 μM



USP210.96 μM



D129758Dorsomorphin 2HCl≥98%1219168-18-95mg,10mg,50mg
AMPK

109 nM

N125522Necrostatin-1≥99%4311-88-010mg,50mg
RIP1
182 nM


G125799Gefitinib (ZD1839)≥99%184475-35-250mg,250mg,1g,5g,25g,100gNR6wtEGFR 细胞EGFR2-37 nM



D139352Dorsomorphin≥98%866405-64-35mg,25mg,100mg
AMPK

109 nM

E125341Everolimus≥98%159351-69-610mg,25mg,100mg
mTOR5-6 nM



A129749Acadesine≥98%2627-69-250mg,250mg,1g






D125110Dasatinib≥99%302962-49-825mg,100mg,500mg,1g,5g
Abl0.6 nM



Src0.8 nM



c-Kit79 nM



c-KitD816V37 nM



V129759Verteporfin≥97%129497-78-510mg,50mg






D125110Dasatinib≥99%302962-49-825mg,100mg,500mg,1g,5g
Abl0.6 nM



Src0.8 nM



c-Kit79 nM



c-KitD816V37 nM



V129759Verteporfin≥97%129497-78-510mg,50mg






D126677DAPT≥98%208255-80-55mg,10mg,25mg,50mg
115 nM



Aβ42200 nM



R126338Ruxolitinib (INCB018424)≥98%941678-49-55mg,25mg,50mg,100mg
JAK13.3 nM



JAK22.8 nM



E121713Etoposide98%33419-42-0100mg,250mg,500mg,1g,5g






A1006255-氮胞苷98%320-67-250mg,250mg,1g,5g,25g





V127521Vemurafenib (PLX4032, RG7204)≥98%918504-65-110mg,25mg,50mg,100mg,500mg,1g,5g
RAFV600E31 nM



c-RAF-148 nM



S134307SB 20219099%152121-30-75mg,25mg,100mg
p38α50 nM



p38β2100 nM



P125167Panobinostat (LBH589)≥98%404950-80-710mg,50mg






I1934916-乙基鹅去氧胆酸98%459789-99-250mg,250mg,1g
FXR
99 nM


C174237CB-83997%1439399-58-2100mg肾脏GLS123 nM



28 nM



GLS2>1 μM



 

*FKBP

项目号产品名称规格CAS包装细胞靶点IC50
S293790Rapamycin≥95%(HPLC)53123-88-950mg,250mg,1gHEK293细胞mTOR~0.1 nM
S115842Rapamycin≥98%(HPLC)53123-88-910mg,25mg,50mg,250mg,1gHEK293细胞mTOR~0.1 nM
E125341Everolimus≥98%159351-69-610mg,25mg,100mg
mTOR5-6 nM
T101159他克莫司分析标准品,≥98%104987-11-310mg---
T101160他克莫司≥98%(HPLC)104987-11-350mg,1g---
F138016他克莫司一水合物≥80.0%(HPLC)109581-93-310mg,50mg,250mg,1g---
A127632Ascomycin≥97.0%104987-12-425mg,100mg,500mg---

 

*LRRK2

项目号产品名称规格CAS包装靶点IC50
L125224LRRK2-IN-1≥99%1234480-84-210mg,50mg,100mgLRRK2 (G2019S)6 nM
LRRK2 (WT)13 nM
G166851GSK2578215A98% (HPLC)1285515-21-05mg,10mg,25mg,50mg,100mgLRRK2 (G2019S)8.9 nM
I129698IKK-16 (IKK Inhibitor VII)≥99%873225-46-810mg,50mgIKK240 nM
IKK complex70 nM
IKK1200 nM
LRRK 250 nM
L125224LRRK2-IN-1≥99%1234480-84-210mg,50mg,100mgLRRK2 (G2019S)6 nM 
LRRK2 (WT)13 nM
G166851GSK2578215A98% (HPLC)1285515-21-05mg,10mg,25mg,50mg,100mgLRRK2~10 nM
G2019S~10 nM

 

*CXCR

项目号产品名称规格CAS包装细胞靶点IC50
T103998单宁酸AR1401-55-410g,25g,100g,250g,500g-CXCR4-
R126706Reparixin≥98%266359-83-55mg,25mg,100mg-CXCR1-
CXCR2-
CXCR8-
P129846Plerixafor 8HCl (AMD3100 8HCl)≥99%155148-31-55mg,10mg,50mg-CXCR444 nM
CXCR125.7 nM
P128026Plerixafor≥98%110078-46-110mg,50mg,250mg无细胞CXCR444 nM
CXCR125.7 nM
D178502danirixin97%954126-98-8100mg-CXCL812.5 nM

 

*Mitophagy

项目号产品名称规格CAS包装细胞靶点IC50
M1294963-甲基腺嘌呤98%5142-23-450mg,250mg,1g,5g,25g
PtdIns3Kγ60 μM
Vps3425 μM
O126162Olaparib (AZD2281, Ku-0059436)≥98%763113-22-010mg,25mg,100mg,250mg,1g
PARP-15 nM
PARP-21 nM
D107159盐酸阿霉素98%25316-40-925mg,100mg,250mg,


S131899SB-203580≥98%(HPLC)152121-47-65mg,25mg,100mg,500mg
SAPK2a/p3850 nM
SAPK2b/p38β2 500 nM
M107827Metformin hydrochloride97%1115-70-45g,25g,100g,500g


U127670U0126-EtOH≥97%1173097-76-125mg,100mg,500mg,
MEK170 nM
MEK260 nM
D137736Dexamethasone98%50-02-21g,25g,100g


A129749Acadesine≥98%2627-69-250mg,250mg,1g


R126338Ruxolitinib (INCB018424)≥98%941678-49-55mg,25mg,50mg,100mg
JAK13.3 nM
JAK2 2.8 nM
E121713Etoposide98%33419-42-0100mg,250mg,500mg,1g,5g


B102375布雷非德菌素 A≥98% (HPLC)20350-15-65mg,25mgHCT 116ATPase0.2 μM
V125336Vorinostat≥99%149647-78-9100mg,500mg,1g,5g


R107315白藜芦醇99%501-36-01g,5g,25g,100g
COX1.1 μM
LOC2.7 μM
R107314白藜芦醇分析标准品501-36-0100mg
COX1.1 μM
LOC2.7 μM
A12697017-AAG98%75747-14-725mg,100mg
HSP905 nM
M118674褪黑素98%73-31-4250mg,1g,5g,25g,100g


 

*Mitophagy

项目号产品名称规格CAS包装靶点IC50
M126461MRT67307≥98%1190378-57-410mg,50mgIKKε 160 nM
TBK-119 nM
ULK145 nM
ULK238 nM


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