Taminadenant (PBF-509; NIR-178) is a novel, oral and potent adenosine receptor antagonist used as an immunotherapy agent. It functions as a strong and specific antagonist of the human A_2A (adenosine 2A) receptor, binding to the receptor with a Ki value of 12 nM. It prevents A_2AR from being expressed on T cells, negating the effect of adenosine and A_2AR on T cell suppression. Additionally, it triggers an immune response by T cells against tumor cells, which in turn slows the growth of tumor cells that are vulnerable to it. It is also mentioned as a possible pro-dopaminergic medication for the treatment of Parkinson's disease (PD).

Physicochemical Properties

Molecular Formula	C10H8BRN7
Molecular Weight	306.127
Exact Mass	305.002
Elemental Analysis	C, 39.24; H, 2.63; Br, 26.10; N, 32.03
CAS #	1337962-47-6
Related CAS #	2253894-78-7 (HCl hydrate); 1337962-47-6; 2253894-81-2 (mesylate); 2253894-80-1 (sulfate); 2253894-79-8 (HCl dihydrate)
PubChem CID	53466958
Appearance	Solid powder
Density	1.9±0.1 g/cm3
Boiling Point	574.9±60.0 °C at 760 mmHg
Flash Point	301.5±32.9 °C
Vapour Pressure	0.0±1.6 mmHg at 25°C
Index of Refraction	1.851
LogP	-0.47
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	2
Heavy Atom Count	18
Complexity	291
Defined Atom Stereocenter Count	0
SMILES	BrC1=C(N)N=C(N=C1N1C=CC=N1)N1C=CC=N1
InChi Key	ATFXVNUWQOXRRU-UHFFFAOYSA-N
InChi Code	InChI=1S/C10H8BrN7/c11-7-8(12)15-10(18-6-2-4-14-18)16-9(7)17-5-1-3-13-17/h1-6H,(H2,12,15,16)
Chemical Name	5-bromo-2,6-di(pyrazol-1-yl)pyrimidin-4-amine
Synonyms	PBF 509; NIR178; PBF509; NIR 178; Taminadenant; PBF-509; NIR-178
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

Targets	Adenosine receptor
ln Vitro	Taminadenant (PBF509) completely blocks agonist-mediated cAMP accumulation, with an IC50 of 72.8 ± 17.4 nM i HEK cells that express human A2ARSNAP permanently[1]. However, it does not demonstrate any agonist efficacy in these cells.
ln Vivo	Taminadenant (PBF509) (0.3, 3, 7.5, 10, or 30 mg/kg; p.o.; single dosage) increases the effects of L-DOPA, exhibits a strong antiparkinsonian activity, and reduces the cataleptic effects of haloperidol[1]. It also lessens the tremulous jaw movement caused by pilocarpine.
Animal Protocol	Sprague-Dawley rats (240-250 g; induced catalepsy by s.c. with 1 mg/kg Haloperidol (HY-14538)) 3, 10, or 30 mg/kg p.o.; single dosage
References	[1]. D1 Agonist Improved Movement of Parkinsonian Nonhuman Primates with Limited DyskinesiaSide Effects. ACS Chem Neurosci. 2020 Feb 19;11(4):560-566.
Additional Infomation	Taminadenant is an orally bioavailable adenosine A2A receptor (A2AR) antagonist, with potential antineoplastic activity. Upon administration, A2AR antagonist PBF-509 selectively binds to and inhibits A2AR expressed on T-lymphocytes. This abrogates the adenosine/A2AR-mediated inhibition of T-lymphocytes and activates a T-cell-mediated immune response against tumor cells, thereby reducing proliferation of susceptible tumor cells. A2AR, a G protein-coupled receptor, is highly expressed on the cell surfaces of T-cells and, upon activation by adenosine, inhibits their proliferation and activation. Adenosine is often produced in excess by cancer cells.

Solubility Data

Solubility (In Vitro)

DMSO: ~125 mg/mL (~408.3 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (6.79 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 20.8 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: ≥ 2.08 mg/mL (6.79 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 20.8 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: ≥ 2.08 mg/mL (6.79 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 20.8 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	3.2666 mL	16.3329 mL	32.6659 mL
	5 mM	0.6533 mL	3.2666 mL	6.5332 mL
	10 mM	0.3267 mL	1.6333 mL	3.2666 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.