BMS-8
目录号 : GC42957
An inhibitor of the PD-1/PD-L1 interaction
Cas No.:1675201-90-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
BMS-8 is a small molecule inhibitor of the interaction between programmed death protein 1 (PD-1) and its ligand programmed cell death ligand 1 (PD-L1) with an IC50 value of 146 nM in a homogeneous time-resolved fluorescence (HTRF) binding assay.
| Cas No. | 1675201-90-7 | SDF | |
| Canonical SMILES | CC1=C(COC2=CC=C(CN3CCCCC3C(O)=O)C=C2Br)C=CC=C1C4=CC=CC=C4 | ||
| 分子式 | C27H28BrNO3 | 分子量 | 494.4 |
| 溶解度 | Methanol: slightly soluble | 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。 |
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| 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 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.0227 mL | 10.1133 mL | 20.2265 mL |
| 5 mM | 0.4045 mL | 2.0227 mL | 4.0453 mL |
| 10 mM | 0.2023 mL | 1.0113 mL | 2.0227 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。
Ultrasensitive electrochemical determination of the cancer biomarker protein sPD-L1 based on a BMS-8-modified gold electrode
Bioelectrochemistry 2021 Jun;139:107742.PMID:33517203DOI:10.1016/j.bioelechem.2021.107742.
This work describes the modification of a gold electrode with the BMS-8 compound that interacts with the Programmed Death-Ligand 1 (PD-L1), an immune checkpoint protein. The results show that we can confirm the presence of the sPD-L1 in the concentration range of 10-18 to 10-8 M using electrochemical impedance spectroscopy (EIS) with a limit of detection (LOD) of 1.87 × 10-14 M for PD-L1 (S/N = 3.3) and at a concentration of 10-14 M via cyclic voltammetry (CV). Additionally, high-resolution X-ray photoelectron spectroscopy (XPS), contact angle, and surface free energy measurements were applied to confirm the functionalization of the electrode. We investigated the selectivity of the electrode for other proteins: Programmed Death-1 (PD-1), cluster of differentiation 160 (CD160), and B- and T-lymphocyte attenuator (BTLA) at concentrations of 10-8 M. Differentiation between PD-L1 and PD-1 was achieved based on the analysis of the capacitance effect frequency dispersion at the surface of the modified Au electrode with BMS-8 after incubation at various concentrations of PD-L1 and PD-1 proteins in the range of 10-18 to 10-8 M. Significant differences were observed in the heterogeneity of PD-L1 and PD-1. The results of the quasi-capacitance studies demonstrate that BMS-8 strongly and specifically interacts with the PD-L1 protein.
Synthesis and Biological Evaluation of Small Molecules as Potential Anticancer Multitarget Agents
Int J Mol Sci 2022 Jun 24;23(13):7049.PMID:35806053DOI:10.3390/ijms23137049.
Twenty-six triazole-based derivatives were designed for targeting both PD-L1 (programmed death receptor ligand 1) and VEGFR-2 (vascular endothelial growth factor receptor 2). These compounds were synthetized and biologically evaluated as multitarget inhibitors of VEGFR-2, PD-L1 and c-Myc proteins. The antiproliferative activity of these molecules on several tumor cell lines (HT-29, A-549, and MCF-7) and on the non-tumor cell line HEK-293 was determined. The effects on the abovementioned biological targets were evaluated for some selected compounds. Compound 23, bearing a p-chlorophenyl group, showed better results than sorafenib in regard to the downregulation of VEGFR-2 and a similar effect to BMS-8 on both PD-L1 and c-Myc proteins. The antiangiogenic and antivascular activities of chloro derivatives were also established by endothelial microtube formation assay on Matrigel®.
Preparation of Biphenyl-Conjugated Bromotyrosine for Inhibition of PD-1/PD-L1 Immune Checkpoint Interactions
Int J Mol Sci 2020 May 21;21(10):3639.PMID:32455628DOI:10.3390/ijms21103639.
Cancer immunotherapy has been revolutionized by the development of monoclonal antibodies (mAbs) that inhibit interactions between immune checkpoint molecules, such as programmed cell-death 1 (PD-1), and its ligand PD-L1. However, mAb-based drugs have some drawbacks, including poor tumor penetration and high production costs, which could potentially be overcome by small molecule drugs. BMS-8, one of the potent small molecule drugs, induces homodimerization of PD-L1, thereby inhibiting its binding to PD-1. Our assay system revealed that BMS-8 inhibited the PD-1/PD-L1 interaction with IC50 of 7.2 μM. To improve the IC50 value, we designed and synthesized a small molecule based on the molecular structure of BMS-8 by in silico simulation. As a result, we successfully prepared a biphenyl-conjugated bromotyrosine (X) with IC50 of 1.5 μM, which was about five times improved from BMS-8. We further prepared amino acid conjugates of X (amino-X), to elucidate a correlation between the docking modes of the amino-Xs and IC50 values. The results suggested that the displacement of amino-Xs from the BMS-8 in the pocket of PD-L1 homodimer correlated with IC50 values. This observation provides us a further insight how to derivatize X for better inhibitory effect.
Novel multitarget inhibitors with antiangiogenic and immunomodulator properties
Eur J Med Chem 2019 May 15;170:87-98.PMID:30878834DOI:10.1016/j.ejmech.2019.03.012.
By means of docking studies, seventeen compounds T.1-T17 have been designed and evaluated as multitarget inhibitors of VEGFR-2 and PD-L1 proteins in order to overcome resistance phenomena offered by cancer. All these designed molecules display a urea moiety as a common structural feature and eight of them (T.1-T8) further contain a 1,2,3-triazol moiety. The antiproliferative activity of these molecules on several tumor cell lines (HT-29, MCF-7, HeLa, A549, HL-60), on the endothelial cell line HMEC-1 and on the non-tumor cell line HEK-293 has been determined. The urea derivatives were also evaluated for their antiangiogenic properties, whereby their ability to inhibit tubulogenesis and kinase activity employing flow cytometry, ELISA, immunofluorescence and western blot techniques was measured. In addition, these techniques were also employed to investigate the immunomodulator action of the synthetic compounds on the inhibition of PD-L1 and c-Myc proteins. Compound T.2, 1-(3-chlorophenyl)-3-(2-(4-(4-methoxybenzyl)-1H-1,2,3-triazol-1-yl)ethyl)urea, has shown similar results to sorafenib in both down-regulation of VEGFR-2 and inhibition of the kinase activity of this receptor. Furthermore, compound T.14, (E)-1-(4-chlorophenyl)-3-(3-(4-methoxystyryl)phenyl)urea, improves the effect of T.2 as regards tube formation of endothelial cells and inhibition of VEGFR-2 tyrosine kinase activity. In addition, T.14 improves the effect of the experimental drug BMS-8 in the inhibition of PD-L1 and c-Myc proteins.
Aryl Urea Based Scaffolds for Multitarget Drug Discovery in Anticancer Immunotherapies
Pharmaceuticals (Basel) 2021 Apr 6;14(4):337.PMID:33917617DOI:10.3390/ph14040337.
Twenty-one styryl and phenethyl aryl ureas have been synthetized and biologically evaluated as multitarget inhibitors of Vascular endothelial growth factor receptor-2 VEGFR-2 and programmed death-ligand-1 (PD-L1) proteins in order to overcome resistance phenomena offered by cancer. The antiproliferative activity of these molecules on several tumor cell lines (HT-29, MCF-7, HeLa and A549), on the endothelial cell line human microvascular endothelial cells (HMEC)-1 and on the non-tumor cell line human embryonic kidney cells (HEK)-293 has been determined. Some derivatives were evaluated for their antiangiogenic properties such as their ability to inhibit microvessel formation using HMEC-1 or their effect on VEGFR-2 in both cancer and endothelial cell lines. In addition, the immunomodulator action of a number of selected compounds was also studied on PD-L1 and c-Myc proteins. Compounds 16 and 23 (Z) and (E)-styryl p-bromophenyl urea, respectively, showed better results than sorafenib in down-regulation of VEGFR-2 and also improved the effect of the anti-PD-L1 compound BMS-8 on both targets, PD-L1 and c-Myc proteins.