BMS-202
(Synonyms: PD1-PDL1抑制剂2, PD-1/PD-L1 inhibitor 2) 目录号 : GC16762
BMS-202是一种非肽性PD-1/PD-L1复合物抑制剂，与PD-L1隔离PD-1/PD-L1二聚体形成（IC50=53.6nM），以结合阻断人PD-1/PD-L1相互作用，从而抑制免疫反应抑制，从而阻止癌细胞逃避抗肿瘤免疫反应。
Cas No.:1675203-84-5
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
BMS-202 is a nonpeptidic PD-1/PD-L1 complex inhibitor binding to PD-L1 and blocks human PD-1/PD-L1 interaction (IC50=53.6nM) to prevent cancer cells from escaping antitumor immune responses[1,2]. The binding of the PD-L1 molecule in the BMS-202/PD-L1 complexes is similar to the binding of the anti-PD-L1 nanobody KN035 and VH domain of avelumab at N-terminal loop in PD-1, occluding the PD-1 interaction surface of PD-L1s[3].
In vitro experiments show that BMS-202 inhibits cell malignancy in human glioblastoma (10μM; 48h)[4]. BMS-202 also suppresses the synthesis and secretion of gonadotropins and enhances apoptosis via p38 MAPK signaling pathway in a mouse pituitary Lβt2 cell model (20μM; 24h)[5]. BMS-202 may act as an inhibitor of programmed cell death ligand (0.1µM, 1µM, 10µM, 100 µM, and 500µM; 48h) in HaCaT immortalized human keratinocytes[6].
In vivo experiments show that BMS-202 performs an anti-tumor effect in the humanized MHC-double knockout NOG mouse (20mg/kg; 9 times; i.v)[7]. BMS-202 also significantly attenuated UV-induced activator protein-1 transcriptional activity in SKH-1 bioluminescent reporter mouse skin (8mM, 200ul; topically introduction on skin)[8].
References:
[1] Liu, Jin et al. “Discovery and Crystallography Study of Novel Biphenyl Ether and Oxadiazole Thioether (Non-Arylmethylamine)-Based Small-Molecule PD-1/PD-L1 Inhibitors as Immunotherapeutic Agents.” *Journal of medicinal chemistry* vol. 66,18 (2023): 13172-13188. doi:10.1021/acs.jmedchem.3c01141
[2] Bailly, Christian, and Gérard Vergoten. “Flurbiprofen as a biphenyl scaffold for the design of small molecules binding to PD-L1 protein dimer.” *Biochemical pharmacology* vol. 178 (2020): 114042. doi:10.1016/j.bcp.2020.114042
[3] Zak, Krzysztof M et al. “Structural Biology of the Immune Checkpoint Receptor PD-1 and Its Ligands PD-L1/PD-L2.” *Structure (London, England : 1993)*vol. 25,8 (2017): 1163-1174. doi:10.1016/j.str.2017.06.011
[4] Yang, Xueou et al. “Metabolic remodeling by the PD-L1 inhibitor BMS-202 significantly inhibits cell malignancy in human glioblastoma.” *Cell death & disease* vol. 15,3 186. 4 Mar. 2024, doi:10.1038/s41419-024-06553-5
[5] Jiang, Ying et al. “The PD-1/PD-L1 binding inhibitor BMS-202 suppresses the synthesis and secretion of gonadotropins and enhances apoptosis via p38 MAPK signaling pathway.” *Drug development research* vol. 83,1 (2022): 176-183. doi:10.1002/ddr.21857
[6] Shafi, Hasham et al. “Comprehensive Advanced Physicochemical Characterization and In Vitro Human Cell Culture Assessment of BMS-202: A Novel Inhibitor of Programmed Cell Death Ligand.” *Pharmaceutics* vol. 16,11 1409. 1 Nov. 2024, doi:10.3390/pharmaceutics16111409
[7] Ashizawa, Tadashi et al. “Antitumor activity of the PD-1/PD-L1 binding inhibitor BMS-202 in the humanized MHC-double knockout NOG mouse.” *Biomedical research (Tokyo, Japan)* vol. 40,6 (2019): 243-250. doi:10.2220/biomedres.40.243
[8]Dickinson, Sally E et al. “Inhibition of UV-Induced Stress Signaling and Inflammatory Responses in SKH-1 Mouse Skin by Topical Small-Molecule PD-L1 Blockade.” *JID innovations : skin science from molecules to population health* vol. 4,2 100255. 5 Jan. 2024, doi:10.1016/j.xjidi.2023.100255
BMS-202是一种非肽性PD-1/PD-L1复合物抑制剂，与PD-L1隔离PD-1/PD-L1二聚体形成（IC50=53.6nM），以结合阻断人PD-1/PD-L1相互作用，从而抑制免疫反应抑制，从而阻止癌细胞逃避抗肿瘤免疫反应[1,2]。PD-L1分子在BMS-202/PD-L1复合物中的结合类似于抗PD-L1纳米体KN035与avelumab在PD-1 n端环上的VH结构域的结合，阻断PD-L1的与PD-1的相互作用表面[3]。
体外实验表明，BMS-202对人胶质母细胞瘤（10μM; 48h）细胞恶性肿瘤有抑制作用[4]。在小鼠垂体l - βt2细胞模型（20μM; 24h）中，BMS-202还能抑制促性腺激素的合成和分泌，并通过p38 MAPK信号通路促进细胞凋亡[5]。BMS-202在HaCaT永活的人角质形成细胞中作为程序性细胞死亡配体的抑制剂（0.1µM, 1µM, 10µM, 100µM和500µM; 48h）[6]。
体内实验表明，BMS-202在人源化mhc双敲除NOG小鼠模型中具有抗肿瘤作用 (20mg/kg; 9次; 静脉注射）[7]。BMS-202还显著降低了SKH-1生物发光报告小鼠皮肤（8mM; 200ul; 局部皮肤涂抹）中紫外线诱导的激活蛋白-1转录活性[8]。
| Cell experiment [1]: | |
Cell lines | U251, LN229, and HEB cells |
Preparation Method | For the cell proliferation assay, 1–1.5 × 103 cells/well were seeded in 96-well plates and cultured for 24h and 48h. The control group included DMEM without BMS-202; the blank group was without any cells or culture media; the vehicle included BMS-202 solution without cells. |
Reaction Conditions | 10μM, 48h incubation |
Applications | BMS-202 apparently inhibits the proliferation of GBM cells both in vitro. |
| Animal experiment [2]: | |
Animal models | SKH-1 mice (Charles River Laboratories, strain code 477) |
Preparation Method | Male transgenic SKH-1 mice heterozygous for the TPA-Response Element–driven luciferase transgene (AP-1 luciferase mice, n=3) were treated topically on their backs with 200 μl of 8 mM BMS-202 or vehicle control (acetone). For all mice receiving BMS-202, the compound was applied twice before (24 hours and 1 hour) as well as immediately after UV exposure. |
Dosage form | 8mM, 200ul, topically introduction on skin |
Applications | UV-induced cleavage of procaspase-3, a hallmark of acute skin photodamage, was attenuated by topical BMS-202.BMS-202 antagonizes UV-induced PD-L1 expression both at the mRNA and protein levels in SKH-1 epidermis. |
References: | |
| Cas No. | 1675203-84-5 | SDF | |
| 别名 | PD1-PDL1抑制剂2, PD-1/PD-L1 inhibitor 2 | ||
| 化学名 | N-(2-(((2-methoxy-6-((2-methyl-[1,1'-biphenyl]-3-yl)methoxy)pyridin-3-yl)methyl)amino)ethyl)acetamide | ||
| Canonical SMILES | CC1=C(COC2=NC(OC)=C(CNCCNC(C)=O)C=C2)C=CC=C1C3=CC=CC=C3 | ||
| 分子式 | C25H29N3O3 | 分子量 | 419.52 |
| 溶解度 | DMSO : 100 mg/mL (238.37 mM), Need ultrasound. | 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 | 2.3837 mL | 11.9184 mL | 23.8368 mL |
| 5 mM | 0.4767 mL | 2.3837 mL | 4.7674 mL |
| 10 mM | 0.2384 mL | 1.1918 mL | 2.3837 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: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet