BMS-200 is a novel and potent small molecule inhibitor of the PD-1/PD-L1 protein protein interaction with IC50 value of 80 nM in cell free assays. Bristol-Myers Squibb was the first to find it. Monoclonal antibodies have significantly improved cancer treatment by blocking the PD-1/PD-L1 immune checkpoint pathway. A number of drawbacks to antibody-based immunotherapies exist, including the high cost of the antibodies, their short half-life, and their immunogenicity. Due to the lack of complete structural knowledge for this pathway, the development of small-molecule PD-1/PD-L1 inhibitors that could overcome these limitations is slow. Bristol-Myers Squibb recently revealed BMS-1001 and its analogs as the first chemical PD-1/PD-L1 inhibitors.

Physicochemical Properties

Molecular Formula	C27H27F2NO6
Molecular Weight	499.503195047379
Exact Mass	499.18
Elemental Analysis	C, 64.92; H, 5.45; F, 7.61; N, 2.80; O, 19.22
CAS #	1675203-82-3
Related CAS #	1675203-82-3
PubChem CID	117941887
Appearance	Solid powder
LogP	1.3
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	9
Rotatable Bond Count	10
Heavy Atom Count	36
Complexity	701
Defined Atom Stereocenter Count	1
SMILES	CC1=C(C=CC=C1C2=CC3=C(C=C2)OCCO3)COC4=C(C=C(C(=C4)F)CNC[C@H](CC(=O)O)O)F
InChi Key	UUBRFEROHJGRBO-FQEVSTJZSA-N
InChi Code	InChI=1S/C27H27F2NO6/c1-16-18(3-2-4-21(16)17-5-6-24-26(10-17)35-8-7-34-24)15-36-25-12-22(28)19(9-23(25)29)13-30-14-20(31)11-27(32)33/h2-6,9-10,12,20,30-31H,7-8,11,13-15H2,1H3,(H,32,33)/t20-/m0/s1
Chemical Name	(3S)-4-[[4-[[3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-methylphenyl]methoxy]-2,5-difluorophenyl]methylamino]-3-hydroxybutanoic acid
Synonyms	BMS-200; BMS 200; BMS200
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	BMS-1001, a novel and potent small molecule inhibitor, has an IC50 value of 2.25 nM in cell-free assays for the PD-1/PD-L1 protein protein interaction.
ln Vivo
Enzyme Assay	BMS recently revealed the first nonpeptidic small molecule inhibitors for the PD-1/PD-L1 pathway that demonstrated activity in a homogeneous time-resolved fluorescence (HTRF) binding assay, but no additional evidence was provided to support their activity.
Animal Protocol
References	[1]. J Med Chem. 2017 Jul 13;60(13):5857-5867; Oncotarget. 2017 Aug 7;8(42):72167-72181; WO/2015034820 A1

Solubility Data

Solubility (In Vitro)

DMSO: ~10mM Water: N/A Ethanol: N/A

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.0020 mL	10.0100 mL	20.0200 mL
	5 mM	0.4004 mL	2.0020 mL	4.0040 mL
	10 mM	0.2002 mL	1.0010 mL	2.0020 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.