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类器官常用小分子及应用文献汇总

2021.2.23

小分子(small molecules)是指分子量小于1000道尔顿(尤其小于400道尔顿),并具有生物学功能的化合物。此类化合物与细胞因子和蛋白不同,其可直接穿过细胞膜进入细胞,进而发挥相应的功能,适用于各种属的细胞。小分子化合物的作用靶点众多,已广泛应用于干细胞,类器官,免疫学,神经生物学,表观遗传学,细胞凋亡,离子通道,肿瘤学和信号转导等生命科学中诸多重要的研究领域。

——类器官培养中常用的小分子:

❶ Gastrin I: 胃泌素是胃肠道一种非常重要的多肽类激素,主要由 G 细胞分泌。肠道及肝脏类器官培养时,需要添加胃泌素来延长类器官的存活时间。

 

❷ A83-01: Activin/NODAL/TGF-beta 通路抑制剂,其抑制 ALK5,ALK4 和 ALK7等激酶。一般用于肝脏、前列腺以及乳腺类器官的培养。

 

❸ Y27632: 是Rho相关丝氨酸-苏氨酸蛋白激酶 (ROCK) 家族的小分子特异性抑制剂,可以阻止干细胞的凋亡,一般在种板培养的第一次加入,后续换液培养不必添加该小分子。

 

❹ SB202190: 是一种高效的 p38 MAPK 抑制剂,靶向作用于 p38α/β。可用于胃肠道、乳腺类器官的培养。

 

❺ Nicotinamide: 是一种B3维生素,是NAD 和 NADP的活性成分,在细胞生理学中发挥重要作用,可用于胃肠道、肝脏以及乳腺类器官的培养。

 

❻ Forskolin: 可以激活腺苷环化酶,常用于提高细胞内 cAMP 的水平。Forskolin 诱导多种类型细胞的分化并激活孕烷X受体 (PXR) 和法尼醇X受体(FXR),可对心脏产生正性肌力作用,并具有血小板抗凝集和降压作用。据报道,它与其他小分子联合使用,可诱导成纤维细胞重编程为诱导多能性干细胞,在肝脏类器官培养的时候必须要添加。

 

❼ Prostaglandin E2: 前列腺素 E2,PGE2。PGE2调节许多生理系统,包括消化系统和免疫系统等。它与特异的受体结合后可介导细胞增殖、分化,在肝脏类器官和前列腺类器官培养时需要添加。

 

❽ CHIR99021: CHIR99021是糖原合成酶激酶3β抑制剂,可诱导人胚胎干细胞向内胚层分化,在肾脏以及视网膜类器官培养时需要。

 

❾ N-acetyl-L-Cysteine: N-乙酰半胱氨酸,它是一种 ROS 抑制剂,具有抗氧化作用,在大多数类器官的培养过程中需要添加。

——类器官培养中常用的小分子列表:

BioGems是PeproTech旗下子公司,BioGems意为生物之珠宝,旨在给客户提供优质的产品,我们全部的产品都在美国进行生产、质控。其小分子产品线覆盖类器官、干细胞、免疫学、神经生物学等研究领域,以其高性价比在市场上占有一席之地。我们坚持以高品质的产品服务于客户,助力您的科学研究!
 
BioGems小分子产品部分参考文献:

1. Acidic Microenvironment Regulates the Severity of Hepatic Ischemia/Reperfusion Injury by Modulating the Generation and Function of Tregs via the PI3K 

X Gan, R Zhang, J Gu, Z Ju, X Wu, Q Wang… - Frontiers in …, 2020

PMID:
https://pubmed.ncbi.nlm.nih.gov/31998287/

…cells were stimulated with phorbol 12-myristate 13-acetate(50 ng/ml, Biogems), ionomycin calcium salt (1 μg/ml, Biogems), and brefeldin A (5 μg/ml, Biogems)…

2. In vivo preclinical evaluation of the new 68Ga-labeled beta-cyclodextrin in prostaglandin E2 (PGE2) positive tumor model using positron emission tomography

G Trencsényi, A Kis, JP Szabó, Á Ráti, K Csige… - International Journal of …, 2020 

PMID:
https://pubmed.ncbi.nlm.nih.gov/31935470/

…Prostaglandin E2 (PGE2; Cat.No.: 3632464) was purchased from Biogems Int. USA…

3. Aligned human cardiac syncytium for in vitro analysis of electrical, structural, and mechanical readouts

BN Napiwocki , D Lang , A Stempien… - Biotechnology and …, 2020

PMID:
https://www.ncbi.nlm.nih.gov/pubmed/32990953/

…12µM of the GSK inhibitor CHIR99021 ( Biogems ) …

4. In vitro expansion of pancreatic islet clusters facilitated by hormones and chemicals

L Jing-Yu, J Cheng, D Ya-Qin, W Pan, Z Zhang… - Cell …, 2020 

PMID:
https://www.ncbi.nlm.nih.gov/pubmed/32284878/

…3 µM CHIR-99021 ( BioGems )…

5. Decreased Foxp3 and function of Tregs caused immune imbalance and liver injury in patients with autoimmune liver diseases post-liver transplantation

Z Liu, J Gu, Z Qin, C Yang, S Yu, X Dai… - Annals of Translational …, 2020

PMID:
https://www.ncbi.nlm.nih.gov/pubmed/32411757/

… For intracellular staining of cytokines, cells were stimulated with phorbol 12-myristate 13-acetate(50 ng/mL, Biogems ), ionomycin calcium salt (1 µg/mL, Biogems ), and brefeldin A (5 µg/mL,Biogems ) for 6 h…

6. An epilepsy‐associated ACTL6B variant captures neuronal hyperexcitability in a human induced pluripotent stem cell model

LY Ahn, GC Coatti, J Liu, E Gumus … - Journal of …, 2020

PMID:
https://www.ncbi.nlm.nih.gov/pubmed/33141462/

…and 10 µM SB431542 ( Biogems ).……

7. 25 (OH) D3 alleviate liver NK cytotoxicity in acute but not in chronic fibrosis model of BALB/c mice due to modulations in vitamin D receptor
A Salhab , J Amer , L Yinying, R Safadi - BMC gastroenterology, 2020

PMID:
https://www.ncbi.nlm.nih.gov/pubmed/32276660/

… and 4week (chronic model). 25(OH) D3 ( Biogems , Cat# 3220632–10 mg) at the…

8. Prohibitin 1 interacts with signal transducer and activator of transcription 3 in T-helper 17 cells
J Zhang, Z Sun, Q Wu, J Shen - Immunology Letters, 2020

PMID:
https://www.ncbi.nlm.nih.gov/pubmed/31899195/

…50 ng/mL phorbol 12-myristate 13-acetate (PMA, Biogems ), 1 μg/mL ionomycin
( Biogems ), and 10 μg/ml brefeldin …

9. Single‐Cell Transcriptomics of Engineered Cardiac Tissues From Patient‐Specific Induced Pluripotent Stem Cell–Derived Cardiomyocytes Reveals Abnormal

YY Lam, W Keung , CH Chan, L Geng… - Journal of the …, 2020

PMID:
https://www.ncbi.nlm.nih.gov/pubmed/33059525/

…and 10 μmol/L Y‐27632( BioGems , Westlake, Village …

10. Implication of IL-17 producing ɑβT and γδT cells in patients with ovarian cancer

X Chen, X Zhang, R Xu, W Shang, W Ming, F Wang… - Human Immunology, 2020 

PMID:
https://www.ncbi.nlm.nih.gov/pubmed/32093885/

…phorbol 12-myristate 13-acetate(50 ng/ml), ionomycin(1 μg/ml), and

brefeldin A (1 μg/ml) (all from Biogems , Rocky Hill, NJ, USA) …

11. In vivo preclinical evaluation of the new 68Ga-labeled beta-cyclodextrin in prostaglandin E2 (PGE2) positive tumor model using positron emission tomography
G Trencsényi , A Kis , JP Szabó, Á Ráti, K Csige… - International Journal of …, 2020

PMID:
https://www.ncbi.nlm.nih.gov/pubmed/31935470/

…Prostaglandin E2(PGE2; Cat.No.: 3632464) was purchased from Biogems …

12. LINE-1 DNA methylation in response to aging and vitamin D

L Ong , S Schibeci, N Fewings , D Booth , G Parnell - bioRxiv, 2020

…Calcitriol(1,25(OH)2Vitamin D3; BioGems) was added at a physiological concentration of 0.1nM…

13. Eosinophil cytolysis on Immunoglobulin G is associated with microtubule formation and suppression of rho‐associated protein kinase signaling

S Esnault , JP Leet, MW Johansson… - Clinical & …, 2020

PMID:
https://www.ncbi.nlm.nih.gov/pubmed/31750580/

… LY294002 (10µM; BioGems , Westlake Village, CA, USA)…

14. miR-155 antagomir protect against DSS-induced colitis in mice through regulating Th17/Treg cell balance by Jarid2/Wnt/β-catenin

F Zhu, H Li, Y Liu, C Tan, X Liu, H Fan, H Wu… - Biomedicine & …, 2020

PMID:
 https://www.ncbi.nlm.nih.gov/pubmed/32135463/

…ionomycin, phorbolmyristate acetate ( BioGems , New Jersey, USA)…

15. Inherent mitochondrial activity influences specification of the germ line in pluripotent stem cells

AM Bothun , DC Woods - Heliyon, 2020

PMID:
https://www.ncbi.nlm.nih.gov/pubmed/32258510/

…supplemented with 400nM PD0325901 ( BioGems Int)…

16. Peptide-Based Scaffolds for the Culture and Transplantation of Human Dopaminergic Neurons

NL Francis, N Zhao, HR Calvelli, A Saini… - … Engineering Part A, 2019

PMID:
https://pubmed.ncbi.nlm.nih.gov/31537172/

…supplemented with 10 μM EC-23 (1044131; Biogems) and 10 μM Y-27632(1293823; Biogems);DOPA2 medium(base medium supplemented with 0.5 μM SAG [9128694; Biogems ])…

17. Human iPSC-derived astrocytes from ALS patients with mutated C9ORF72 show increased oxidative stress and neurotoxicity
A Birger, I Ben-Dor, M Ottolenghi, T Turetsky, Y Gil… - EBioMedicine, 2019

PMID:
https://pubmed.ncbi.nlm.nih.gov/31787569/

…supplemented with 10 μM SB431542 (Biogems,Westlake Village, CA, USA) …

18. Elevated TIM3 expression of T helper cells affects immune system in patients with myelodysplastic syndrome
R Fu, L Li, J Hu, Y Wang, J Tao, H Liu, Z Liu… - Journal of Investigative …, 2019

PMID:
https://pubmed.ncbi.nlm.nih.gov/31511310/

…Phorbol 12-myristate 13-acetate (1µg/mL) (PMA) and ionomycin (50 µg/mL) (Biogems, Pepro Tech, USA) …

19 Prohibitin 1 interacts with signal transducer and activator of transcription 3 in T-helper 17 cells
J Zhang, Z Sun, Q Wu, J Shen - Immunology Letters, 2020

PMID:
 https://pubmed.ncbi.nlm.nih.gov/31899195/

…phorbol 12-myristate 13-acetate(PMA, Biogems),1 μg/mL ionomycin(Biogems) …

20. FMR1 Reactivating Treatments in Fragile X iPSC-Derived Neural Progenitors In Vitro and In Vivo

D Vershkov, N Fainstein, S Suissa, T Golan-Lev… - Cell reports, 2019

PMID:

https://pubmed.ncbi.nlm.nih.gov/30840878/

…SB431542, Biogems, Cat# 3014193. LDN-193189, Biogems, Cat#1066208…

21. Eosinophil cytolysis on Immunoglobulin G is associated with microtubule formation and suppression of rho‐associated protein kinase signalling

S Esnault, JP Leet, MW Johansson… - Clinical & …, 2019

PMID:
https://pubmed.ncbi.nlm.nih.gov/31750580/

…LY294002 (10µM; BioGems, Westlake Village, CA, USA) …

22. HIF1α-Dependent Metabolic Signals Control the Differentiation of Follicular Helper T Cells
L Dong, Y He, S Zhou, Y Cao, Y Li, Y Bi, G Liu - Cells, 2019

PMID:
https://pubmed.ncbi.nlm.nih.gov/31744227/

…cells were stimulated with phorbol-12-myristate-13-acetate (PMA;Sigma-Aldrich) and ionomycin (PeproTech-BioGems, NJ, USA) …

23. Size-dependent cortical compaction induces metabolic adaptation in mesenchymal stem cell aggregates

BM Bijonowski, SI Daraiseh, X Yuan… - Tissue Engineering Part …, 2019

PMID:
https://pubmed.ncbi.nlm.nih.gov/30187829/

…Y27632 dichloride and Gleevec(Imatinib Mesylate) (Biogems, Westlake Village, CA)…

24. Generation of a PDX1–EGFP reporter human induced pluripotent stem cell line, KSCBi005-A-3, using the CRISPR/Cas9 system

Y Lee, HY Choi, A Kwon, H Park, MH Park, JW Kim… - Stem cell …, 2019

PMID:
https://pubmed.ncbi.nlm.nih.gov/31683099/

…and 10 μM Alk5 inhibitor (BioGems) for 5 days during…

25. The imbalance between regulatory and memory B cells accompanied by an increased number of circulating T-follicular helper cells in MOG–antibody-associated
X Li, L Wang, L Zhou, J ZhangBao, MZ Miao… - Multiple sclerosis and …, 2019

PMID:
https://pubmed.ncbi.nlm.nih.gov/31546225/

…25 ng/mL Phorbol 12-myristate 13-acetate(PMA), 2 μg/mL Ionomycin and 10 μg/mL Brefeldin A (BFA) (BioGems, Westlake Village…

26. Adoptive transfer of DMSO-induced regulatory T cells exhibits a similar preventive effect compared to an in vivo DMSO treatment for chemical-induced experimental Encapsulating Peritoneal Sclerosis in Mice

GJ Lin, CH Wu, CC Yu, JR Lin, XD Liu, YW Chen… - Toxicology and applied …, 2019

PMID:
https://pubmed.ncbi.nlm.nih.gov/31254568

…Rapamycin (BioGems, Westlake Village, CA USA) …

27. Immune effects of glycolysis or oxidative phosphorylation metabolic pathway in protecting against bacterial infection

Y Li, A Jia, Y Wang, L Dong, Y Wang… - Journal of cellular …, 2019

PMID:
https://pubmed.ncbi.nlm.nih.gov/30972784/

…Phorbol‐12‐myristate‐13‐acetate (PMA; Sigma‐Aldrich) with ionomycin (Peprotech‐Biogems,NJ) … 

28. Size-dependent Cortical Compaction Induces Metabolic Adaptation in Mesenchymal Stem Cell Aggregates
BM Bijonowski, SI Daraiseh, X Yuan, T Ma - Tissue Engineering, 2018

PMID:
https://www.ncbi.nlm.nih.gov/pubmed/30187829/

…Y27632 dichloride and Gleevec(Imatinib Mesylate) (Biogems, Westlake Village)…

29. Oxymatrine Inhibits Transforming Growth Factor β1 (TGF-β1)-Induced Cardiac Fibroblast-to-Myofibroblast Transformation (FMT) by Mediating the Notch …
L Zhao, Y Xu, L Tao, Y Yang, X Shen… - … medical journal of …, 2018

PMID:
https://www.ncbi.nlm.nih.gov/pubmed/30196308/

…DAPT was from BioGems, USA…

30. A microfluidic platform to study the effects of GDNF on neuronal axon entrapment

ZZ Wang, MD Wood, SE Mackinnon… - Journal of neuroscience …, 2018

PMID:
https://www.ncbi.nlm.nih.gov/pubmed/30081039/

…Then the plate was supplemented with 2 μM forskolin (BioGems, CA,USA) …

31. Effect of erythropoietin production induced by hypoxia on autophagy in HepG2 cells
K Nishimura, K Goto, H Nakagawa - Biochemical and biophysical research …, 2018

PMID:
https://www.ncbi.nlm.nih.gov/pubmed/29191652/

… 3-Methyladenine (3-MA) was purchased from BioGems International Inc. (Westlake Village, CA)…

32. An integrated biomanufacturing platform for the large-scale expansion and neuronal differentiation of human pluripotent stem cell-derived neural progenitor cells
G Srinivasan, D Morgan, D Varun, N Brookhouser… - Acta biomaterialia, 2018

PMID:
 https://www.ncbi.nlm.nih.gov/pubmed/29775730/

…Cells were then detached with Accutase (ThermoFisher) and resuspended in E8 media supplemented with 5 μM Rho kinase inhibitor(ROCKi; Y-27632 [BioGems]) …

33. ALS-related human cortical and motor neurons survival is differentially affected by Sema3A
A Birger, M Ottolenghi, L Perez, B Reubinoff… - Cell death & …, 2018

PMID:
https://www.ncbi.nlm.nih.gov/pubmed/29449528/

…NSC medium was supplementedwith 5 μM SB431542 (Biogems, Westlake Village, CA, USA)…

34. Generation and characterization of human induced pluripotent stem cell (hiPSC) lines from an Alzheimer's disease (ASUi003-A) and non-demented control …

N Brookhouser, P Zhang, R Caselli … - Stem cell …, 2017 

PMID:
https://www.ncbi.nlm.nih.gov/pubmed/29246571/

… hiPSCs were passaged every 4–5 days with Accutase (Thermo Fisher)and 5 μM Rho kinase inhibitor (Y-27632; Biogems)…

35. Macrophage inflammatory Protein-2 in high mobility group box 1 secretion of macrophage cells exposed to Lipopolysaccharide

Q Chaochao, G Lou, Y Yang, Y Liu, Y Hu… - Cellular Physiology and …, 2017

PMID:
https://www.ncbi.nlm.nih.gov/pubmed/28662496/

… MAPK inhibitors SP600125, PD98059, and SB203580 and the PI3K/Akts inhibitor LY294002 were obtained from BioGems…


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