BIO 5192是一种具有强效选择性的小分子整合素α4β1（VLA-4）抑制剂，IC50值为1.8nM。
Cas No.:327613-57-0
Sample solution is provided at 25 µL, 10mM.
_1-3.$$$39978408@51.jpg');)
_1-9.$$$38538795@65.jpg');)
_1-9.$$$39112701@51.jpg');)
_1-7.$$$37316672@70.jpg');)
_366-372.$$$36198801@70.jpg');)
.$$$38565142@65.jpg');)
_1867-1883.$$$33248023@67.jpg');)
_eads6055.$$$39977546@45.jpg');)
_eadm9805.$$$40080571@45.jpg');)
_eadj3020.$$$39666821@45.jpg');)
_1-20.$$$39757301@28.jpg');)
_1-24.$$$38898113@28.jpg');)
_273-287.$$$36806353@46.jpg');)
_1-16.$$$37156877@44.jpg');)
_1-19.$$$37460805@44.jpg');)
_1291-1307.$$$34518654@46.jpg');)
BIO 5192 is a potent and selective small-molecule inhibitor of integrin α4β1 (VLA-4), with an IC50 value of 1.8nM[1]. VLA-4 is a crucial cell adhesion molecule on immune cells (e.g., lymphocytes, monocytes, eosinophils) that enables their adhesion to the vascular endothelium and migration into tissues, which is vital for immune cell trafficking, hematopoietic regulation, and immune response activation[2]. BIO 5192 is commonly used in research on mobilizing hematopoietic stem and progenitor cells (HSPCs), autoimmune diseases like multiple sclerosis, and potential hematological disorders (by preventing cell adhesion)[3,4].
In vitro, pretreatment of mouse myeloma WT 5TGM1-GFP cells with BIO 5192 (100nM) for 30min significantly inhibited the binding of the fluorescent probe LLP2A-Cy5 to cell surface VLA-4[5]. Pretreatment of human T lymphocytes with BIO 5192 (10μg/mL) for 5min markedly suppressed VLA-4-mediated adhesion of lymphocytes to TNF-α-activated human umbilical vein endothelial cells (HUVECs) and prevented the co-recruitment of VCAM-1 at endothelial cell contact sites[6].
In vivo, a single intravenous injection of BIO 5192 (1mg/kg) in mice induced only a moderate increase in the numbers of progenitor cells and hematopoietic stem cells (HSCs) in peripheral blood after 1h, demonstrating a relatively weak mobilization effect[7]. Combined treatment of mice with BIO 5192 (1mg/kg; i.v.) and Plerixafor (5mg/kg; s.c.) produced an additive effect on HSPC mobilization. The mobilization level peaked at 3h and persisted for at least 6h, with the effect being significantly superior to either drug alone[3].
References:
[1] LEONE D R, GIZA K, GILL A, et al. An assessment of the mechanistic differences between two integrin α4β1 inhibitors, the monoclonal antibody TA-2 and the small molecule BIO5192, in rat experimental autoimmune encephalomyelitis[J]. The Journal of Pharmacology and Experimental Therapeutics, 2003, 305(3): 1150-1162.
[2] OOSTENDORP R A J, DÖRMER P. VLA-4-mediated interactions between normal human hematopoietic progenitors and stromal cells[J]. Leukemia & Lymphoma, 1997, 24(5-6): 423-435.
[3] RAMIREZ P, RETTIG M P, UY G L, et al. BIO5192, a small molecule inhibitor of VLA-4, mobilizes hematopoietic stem and progenitor cells[J]. Blood, The Journal of the American Society of Hematology, 2009, 114(7): 1340-1343.
[4] THEIEN B E, VANDERLUGT C L, NICKERSON-NUTTER C, et al. Differential effects of treatment with a small-molecule VLA-4 antagonist before and after onset of relapsing EAE[J]. Blood, 2003, 102(13): 4464-4471.
[5] HATHI D, CHANSWANGPHUWANA C, CHO N, et al. Ablation of VLA4 in multiple myeloma cells redirects tumor spread and prolongs survival[J]. Scientific Reports, 2022, 12(1): 30.
[6] BARREIRO O, ZAMAI M, YANEZ-MO M, et al. Endothelial adhesion receptors are recruited to adherent leukocytes by inclusion in preformed tetraspanin nanoplatforms[J]. The Journal of Cell Biology, 2008, 183(3): 527-542.
[7] CAO B, ZHANG Z, GRASSINGER J, et al. Therapeutic targeting and rapid mobilization of endosteal HSC using a small molecule integrin antagonist[J]. Nature Communications, 2016, 7(1): 11007.
BIO 5192是一种具有强效选择性的小分子整合素α4β1（VLA-4）抑制剂，IC50值为1.8nM[1]。VLA-4是免疫细胞（淋巴细胞、单核细胞、嗜酸性粒细胞等）上的关键细胞粘附分子，可帮助它们粘附在血管壁（内皮）并进入组织，对免疫细胞运输、造血调控和免疫反应激活至关重要[2]。BIO 5192通常用于动员造血干细胞和祖细胞（HSPCs）、多发性硬化症等自身免疫疾病及潜在血液疾病（通过防止细胞粘连）的研究[3,4]。
在体外，BIO 5192（100nM）预处理小鼠骨髓瘤WT 5TGM1-GFP细胞30min，显著抑制了荧光探针LLP2A-Cy5与细胞表面VLA-4的结合[5]。BIO 5192（10μg/mL）预处理人类T淋巴细胞5min，显著抑制了VLA-4介导的淋巴细胞与TNF-α活化的人脐静脉内皮细胞（HUVECs）之间的粘附，并阻止了VCAM-1在内皮细胞接触部位的共募集[6]。
在体内，BIO 5192（1mg/kg）单次静脉注射处理小鼠，1h后仅中度增加外周血中的祖细胞和造血干细胞（HSC）数量，动员效果较弱[7]。BIO 5192（1mg/kg; i.v.）与Plerixafor（5mg/kg; s.c.）联合处理小鼠，对HSPCs的动员产生叠加效应，动员水平在3h达到峰值并持续至少6h，效果显著优于单药[3]。
| Cell experiment [1]: | |
Cell lines | Human T lymphoblasts |
Preparation Method | Human T lymphoblasts were pretreated (5min) with 10μg/ml BIO 5192 to inactivate VLA-4 and were added to TNF-α-activated HUVECs for 5min. After incubation, samples were washed and fixed in 4% paraformaldehyde and processed for immunofluorescence. A series of optical sections were obtained at 21℃ with a confocal laser-scanning unit coupled to a microscope using an HCX PL APO CS 63× NA 1.3 glycerol immersion objective. Images were analyzed with confocal software. |
Reaction Conditions | 10μg/mL; 5min |
Applications | BIO 5192 treatment significantly inhibited VLA-4-mediated adhesion between lymphocytes and TNF-α-activated HUVECs and prevented the co-recruitment of VCAM-1 at endothelial cell contact sites. |
| Animal experiment [2]: | |
Animal models | C57BL/6J × 129Sv/J F1 mice |
Preparation Method | C57BL/6J × 129Sv/J F1 mice were injected intravenously with a single dose of 1mg/kg BIO 5192 and subcutaneously with a single dose of 5mg/kg Plerixafor, and peripheral blood was collected for HSPC mobilization analysis using colony-forming unit granulocyte-macrophage (CFU-GM) assays. |
Dosage form | 1mg/kg; i.v. |
Applications | The combined treatment of mice with BIO 5192 and Plerixafor produced an additive effect on the mobilization of HSPCs, with the mobilization level reaching its peak at 3h and lasting for at least 6h, which was significantly better than that of the single drug. |
References: | |
| Cas No. | 327613-57-0 | SDF | |
| 化学名 | (S)-2-((S)-1-((3,5-dichlorophenyl)sulfonyl)pyrrolidine-2-carboxamido)-4-((S)-4-methyl-2-(N-methyl-2-(4-(3-(o-tolyl)ureido)phenyl)acetamido)pentanamido)butanoic acid | ||
| Canonical SMILES | ClC1=CC(Cl)=CC(S(=O)(N2[C@H](C(N[C@H](C(O)=O)CCNC([C@H](CC(C)C)N(C)C(CC(C=C3)=CC=C3NC(NC4=CC=CC=C4C)=O)=O)=O)=O)CCC2)=O)=C1 | ||
| 分子式 | C38H46Cl2N6O8S | 分子量 | 817.78 |
| 溶解度 | <81.78mg/ml in DMSO; <40.89mg/ml in 1eq. NaOH | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 1.2228 mL | 6.1141 mL | 12.2282 mL |
| 5 mM | 244.6 μL | 1.2228 mL | 2.4456 mL |
| 10 mM | 122.3 μL | 611.4 μL | 1.2228 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >97.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet