PD-1/PD-L1-IN-13 (Compound 43) is a potent immune checkpoint PD-1/PD-L1 PPI inhibitor (antagonist) with IC50 of 10.2 nM for PD-1/PD-L1 interaction. PD-1/PD-L1-IN-13 promotes CD8+ T cell activation and delays tumor growth in a Hepa1-6 syngeneic mouse model.

Physicochemical Properties

Molecular Formula	C36H34CLF2N3O9
Molecular Weight	726.119676113129
Exact Mass	725.195
CAS #	2865841-81-0
PubChem CID	162679299
Appearance	White to off-white solid powder
LogP	4.1
Hydrogen Bond Donor Count	5
Hydrogen Bond Acceptor Count	14
Rotatable Bond Count	11
Heavy Atom Count	51
Complexity	1170
Defined Atom Stereocenter Count	4
SMILES	CC1=C(C=CC=C1C(OC2=C(C=C(C(=C2)OCC3=CC(=NC=C3)C#N)CN[C@H]4[C@H]([C@@H]([C@H](OC4O)CO)O)O)Cl)(F)F)C5=CC6=C(C=C5)OCCO6
InChi Key	TUOSAPKOJRLJAP-JZFXKNFZSA-N
InChi Code	InChI=1S/C36H34ClF2N3O9/c1-19-24(21-5-6-27-30(13-21)48-10-9-47-27)3-2-4-25(19)36(38,39)51-29-14-28(49-18-20-7-8-41-23(11-20)15-40)22(12-26(29)37)16-42-32-34(45)33(44)31(17-43)50-35(32)46/h2-8,11-14,31-35,42-46H,9-10,16-18H2,1H3/t31-,32+,33-,34-,35?/m1/s1
Chemical Name	4-[[4-chloro-5-[[3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-methylphenyl]-difluoromethoxy]-2-[[[(3S,4R,5S,6R)-2,4,5-trihydroxy-6-(hydroxymethyl)oxan-3-yl]amino]methyl]phenoxy]methyl]pyridine-2-carbonitrile
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

References

[1]. Design, Synthesis, and Pharmacological Evaluation of Biaryl-Containing PD-1/PD-L1 Interaction Inhibitors Bearing a Unique Difluoromethyleneoxy Linkage. J Med Chem. 2021;64(22):16687-16702.

Solubility Data

Solubility (In Vitro)

DMSO: 150 mg/mL (206.58 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 3.75 mg/mL (5.16 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 37.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 3.75 mg/mL (5.16 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 37.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 3: ≥ 3.75 mg/mL (5.16 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 37.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.3772 mL	6.8859 mL	13.7718 mL
	5 mM	0.2754 mL	1.3772 mL	2.7544 mL
	10 mM	0.1377 mL	0.6886 mL	1.3772 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.