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BMS-1001 HCl

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Chemical Structure| 2113650-04-5 同义名 : BMS-1001 (hydrochloride);BMS-1001 hydrochloride
CAS号 : 2113650-04-5
货号 : A1216708
分子式 : C35H35ClN2O7
纯度 : 99%+
分子量 : 631.115
MDL号 : MFCD32690091
存储条件：

粉末 Inert atmosphere,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 12 mg/mL(19.01 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 The membrane-bound molecules programmed death 1 (PD-1) and its ligand PD-L1 (PD-1/PD-L1) belong to the immune checkpoint pathway. PD-1 pathway downregulates effector T cells in immune response, thereby causing immune suppression[1]. PD-1/PD-L1 both regulates and is regulated by cellular signaling pathways and epigenetic modification, thus inhibiting the proliferation and effector function of T and B cells. The lack of tumor antigens and effective antigen presentation, aberrant activation of oncogenic pathways, mutations in IFN-γ signaling, immunosuppressive tumor microenvironment such as regulatory T cells, myeloid-derived suppressor cells, M2 macrophages, and immunoinhibitory cytokines can lead to resistance to PD-1/PD-L1 blockade[2]. In a steady state, the interaction of PD-1 with its ligands PD-L1 (B7-H1, CD274) and PD-L2 (B7-DC, CD273) maintains peripheral immune tolerance. However, the expression of PD-L1 on tumor cells and interaction with PD-1 on T cells dampen anti-tumor immunity[3]. PI3K/Akt/mTOR and MAPK signal network induces PD-1/PD-L1 expression and facilitates tumor progression. Transcriptional factors such as hypoxia induced factors, PTEN, p53, CDK5, BRD4, STAT modulate PD-1/PD-L1 expression. PD-1/PD-L1 level is also regulated via epigenetic and post-translational manner[4]. BMS-1001 hydrochloride is an orally active human PD-L1/PD-1 immune checkpoint inhibitor. BMS-1001 hydrochloride exhibits low-toxicity in cells. BMS-1001 binds to human PD-L1 and blocks its interaction with PD-1. BMS-1001 presents low toxicity towards tested cell lines and block the interaction of soluble PD-L1 with the cell surface-expressed PD-1. BMS-1001 alleviates the inhibitory effect of the soluble PD-L1 on the T-cell receptor-mediated activation of T-lymphocytes[5].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.58mL

0.32mL

0.16mL

7.92mL

1.58mL

0.79mL

15.84mL

3.17mL

1.58mL
参考文献

[1]Xinxin Zhu,et al. Soluble PD-1 and PD-L1: predictive and prognostic significance in cancer. Oncotarget. 2017 May 31;8(57):97671-97682.

[2]Jie Bai,et al. Regulation of PD-1/PD-L1 pathway and resistance to PD-1/PD-L1 blockade. Oncotarget. 2017 Nov 25;8(66):110693-110707.

[3]Qi Wang,et al. The PD-1 Interactome. Adv Biol (Weinh). 2021 Jun 25;e2100758.

[4]Jie-Ming Ni,et al. Landscape of PD-1/PD-L1 Regulation and Targeted Immunotherapy. Chin Med Sci J. 2018 Sep 20;33(3):174-182.

[5]Skalniak L, et al. Small-molecule inhibitors of PD-1/PD-L1 immune checkpoint alleviate the PD-L1-induced exhaustion of T-cells. Oncotarget. 2017 Aug 7;8(42):72167-72181.