WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H561499
CAS#: 1675203-84-5
Description: BMS-202 is a PD-1/PD-L1 interaction inhibitor. BMS-202 binds to and induces dimerization of PD-L1, an inhibitory immune checkpoint protein.
Hodoodo Cat#: H561499
Name: BMS-202
CAS#: 1675203-84-5
Chemical Formula: C25H29N3O3
Exact Mass: 419.22
Molecular Weight: 419.520
Elemental Analysis: C, 71.57; H, 6.97; N, 10.02; O, 11.44
Synonym: BMS-202; BMS 202; BMS202;
IUPAC/Chemical Name: N-(2-{[2-Methoxy-6-(2-methyl-biphenyl-3-ylmethoxy)-pyridin-3-ylmethyl]-amino}-ethyl)-acetamide
InChi Key: JEDPSOYOYVELLZ-UHFFFAOYSA-N
InChi Code: InChI=1S/C25H29N3O3/c1-18-22(10-7-11-23(18)20-8-5-4-6-9-20)17-31-24-13-12-21(25(28-24)30-3)16-26-14-15-27-19(2)29/h4-13,26H,14-17H2,1-3H3,(H,27,29)
SMILES Code: CC(NCCNCC1=CC=C(OCC2=C(C)C(C3=CC=CC=C3)=CC=C2)N=C1OC)=O
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info:
| Biological target: | BMS-202 is a potent and nonpeptidic PD-1/PD-L1 complex inhibitor with an IC50 of 18 nM and a KD of 8 μM. |
| In vitro activity: | In order to investigate cytotoxicity of PCC0208025 (BMS202), both tumor cells and CD3+ cells were exposed to different concentrations of PCC0208025. The results in Table 1 showed that IC50 were above 10.0 μM to mice tumor cells and human CD3+ cells, which indicates PCC0208025 possesses low cytotoxicity in vitro. The effects of PCC0208025 on the production of cytokine IFN-γ in human CD3+ cells in vitro were also investigated. As shown in Fig 3, combined aCD3 and aCD28 significantly increased the IFN-γ expression compared with medium control (each treatment P < 0.05, n = 6), which was significantly decreased by human PDL1 protein (each treatment P < 0.05, n = 6). However, anti-PD-L1 antibody BMS-936559 and the compound PCC0208025 from 0.01 to 1 μM markedly rescued PD-L1-mediated inhibition of IFN-γ production (each treatment P < 0.05, respectively, n = 6). PLoS One. 2020; 15(3): e0228339. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098565/ |
| In vivo activity: | The anti-cancer activities of PCC0208025 in B16-F10-bearing mice was investigated. It was found that treatment with PCC0208025 at 30 mg/kg and 60 mg/kg significantly decreased tumor weight (P < 0.05, n = 8) and tumor volumes (day 20, P < 0.05, n = 8) compared with the control group (Fig 4A and 4B). According to tumor weight, 30 mg/kg and 60 mg/kg of PCC0208025 presented the IR of 30.3% and 50.1%, respectively. To investigate the effects of PCC0208025 on the immune function in B16-F10-bearing mice, the plasma IFN-γ level was detected using mice ELISA kit. As shown in Fig 5, PCC0208025 of 30 and 60 mg/kg markedly elevated plasma IFN-γ levels compared with the control group (each treatment P < 0.05, n = 6). The work suggests that PCC0208025 exhibited anti-tumor effects in B16-F10 tumor isograft model through inhibiting Treg expansion and increasing cytotoxic activity of tumorinfiltrating CD8+ T cells by the blockade of PD-1/PD-L1 binding, which provides the pharmacological basis to develop small molecule inhibitors for PD-1/PD-L1 interactions for PCC0208025 as a lead compound. PLoS One. 2020; 15(3): e0228339. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098565/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 62.0 | 146.99 |
The following data is based on the product molecular weight 419.52 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Ashizawa T, Iizuka A, Tanaka E, Kondou R, Miyata H, Maeda C, Sugino T, Yamaguchi K, Ando T, Ishikawa Y, Ito M, Akiyama Y. Antitumor activity of the PD-1/PD-L1 binding inhibitor BMS-202 in the humanized MHC-double knockout NOG mouse. Biomed Res. 2019;40(6):243-250. doi: 10.2220/biomedres.40.243. PMID: 31839668. 2. Hu Z, Yu P, Du G, Wang W, Zhu H, Li N, Zhao H, Dong Z, Ye L, Tian J. PCC0208025 (BMS202), a small molecule inhibitor of PD-L1, produces an antitumor effect in B16-F10 melanoma-bearing mice. PLoS One. 2020 Mar 26;15(3):e0228339. doi: 10.1371/journal.pone.0228339. Erratum in: PLoS One. 2021 Apr 28;16(4):e0251020. PMID: 32214351; PMCID: PMC7098565. |
| In vitro protocol: | 1. Ashizawa T, Iizuka A, Tanaka E, Kondou R, Miyata H, Maeda C, Sugino T, Yamaguchi K, Ando T, Ishikawa Y, Ito M, Akiyama Y. Antitumor activity of the PD-1/PD-L1 binding inhibitor BMS-202 in the humanized MHC-double knockout NOG mouse. Biomed Res. 2019;40(6):243-250. doi: 10.2220/biomedres.40.243. PMID: 31839668. 2. Hu Z, Yu P, Du G, Wang W, Zhu H, Li N, Zhao H, Dong Z, Ye L, Tian J. PCC0208025 (BMS202), a small molecule inhibitor of PD-L1, produces an antitumor effect in B16-F10 melanoma-bearing mice. PLoS One. 2020 Mar 26;15(3):e0228339. doi: 10.1371/journal.pone.0228339. Erratum in: PLoS One. 2021 Apr 28;16(4):e0251020. PMID: 32214351; PMCID: PMC7098565. |
| In vivo protocol: | 1. Ashizawa T, Iizuka A, Tanaka E, Kondou R, Miyata H, Maeda C, Sugino T, Yamaguchi K, Ando T, Ishikawa Y, Ito M, Akiyama Y. Antitumor activity of the PD-1/PD-L1 binding inhibitor BMS-202 in the humanized MHC-double knockout NOG mouse. Biomed Res. 2019;40(6):243-250. doi: 10.2220/biomedres.40.243. PMID: 31839668. 2. Hu Z, Yu P, Du G, Wang W, Zhu H, Li N, Zhao H, Dong Z, Ye L, Tian J. PCC0208025 (BMS202), a small molecule inhibitor of PD-L1, produces an antitumor effect in B16-F10 melanoma-bearing mice. PLoS One. 2020 Mar 26;15(3):e0228339. doi: 10.1371/journal.pone.0228339. Erratum in: PLoS One. 2021 Apr 28;16(4):e0251020. PMID: 32214351; PMCID: PMC7098565. |
1: Zak KM, Grudnik P, Magiera K, Dömling A, Dubin G, Holak TA. Structural Biology of the Immune Checkpoint Receptor PD-1 and Its Ligands PD-L1/PD-L2. Structure. 2017 Aug 1;25(8):1163-1174. doi: 10.1016/j.str.2017.06.011. Review. PubMed PMID: 28768162.
