Adenosine A₃ receptor (A₃R) Antagonist

Derenofylline (SLV 320) is a potent, selective and orally active adenosine A₁ receptor antagonist, with K_i values of 1 nM, 200 nM and 398 nM for human A₁, A₃ and A_2A receptors respectively. Derenofylline suppresses cardiac fibrosis and attenuates albuminuria without affecting blood pressure in rats.

DPTN is a potent and selective human, mouse, and rat A³AR antagonist with K_i values of 1.65, 9.61, and 8.53 nM, respectively.

PSB36 is a highly selective A₁ adenosine receptor antagonist, with a K_i of 0.12 nM and a K_d of 0.7 nM. Systemic administration of PSB36 reduces formalin- and Carrageenan (HY-125474)-induced edema in mice and decreases pain-related behaviors, with no local paw activity. PSB36 prolongs the APD₉₀ of rat and human atria, produces a frequency-dependent prolongation of rat atrial ERP, increases the diastolic threshold of rat atria, and shortens the duration of atrial fibrillation episodes. PSB36 can be used in research related to inflammatory pain, inflammatory hyperalgesia, edema and atrial fibrillation.

VUF-5574 is a selective antagonist of adenosine A³ receptor with a K_i of 4.03 nM for the recombinant human receptor.

A3AR antagonist-8 is a selective A3 adenosine receptor antagonist with a K_i of 98 nM for human A3 adenosine receptor. A3AR antagonist-8 can be used for the research of glaucoma, chronic renal disease, acute renal ischemia and reperfusion injury, and cancer.

MK-1088 is an orally active A_2A/A_2B adenosine receptor antagonist with human A_2A K_i of 0.31 nM, human A_2B K_i 5.3 nM. MK-1088 blocks receptor downstream signaling, inhibits CREB phosphorylation and reverses adenosine-mediated immunosuppression. MK-1088 restores TNF−α release and enhances tumor immune surveillance. MK-1088 can be used for the research of cancer^[1].

LUF5437 is a potent and selective adenosine A₁ receptor antagonist with a rat K_i of 7.3 nM. LUF5437 can be used for research on cardiovascular and neurological diseases.

MRS1334 is a potent and selective human adenosine A₃ receptor antagonist with K_is of 2.69 nM, >100 nM, >100 nM for hA₃, rA₁, rA_2A, respectively. MRS1334 blocks the protective effect of Cl-IB-MECA leading to significant bradycardia and elevated ST segment. MRS1334 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

A2A receptor antagonist 3 (Example 92) is an adenosine A2a receptor antagonist with a K_i of 0.4 nM. A2A receptor antagonist 3 also binds to A2b, A1 and A3 receptor with K_is of 37, 107 and 1467 nM, respectively.

PSB11 hydrochloride is an antagonist with reverse excitatory activity for human A3 Adenosine Receptor with high affinity (K_i=2.3 nM).

LAS38096 is a potent, selective, and efficacious A2B Adenosine Receptor antagonist, with a K_i of 17 nM.

Adenosine receptor antagonist 5 (Compound 39) is a selective antagonist for human adenosine A3 receptor (hA3R) with K_i of 12 nM. Adenosine receptor antagonist 5 inhibits IB-MECA (HY-13591)-induced cAMP accumulation in NCI-H1792 cell, inhibits the proliferation of cancer cell LK-2 and NCI-H1792. Adenosine receptor antagonist 5 exhibits a fast metabolic rate in human liver microsomes.

MRS542 is a nucleoside A3 AR antagonist with a pK_i of 8.74. MRS542 also acts as a partial agonist (pEC₅₀ = 7.76) in promoting β-arrestin translocation. MRS542 can be converted into an agonist by LUF6000 (HY-13236). MRS542 can be used for cardiovascular disease research.

A2AAR antagonist 4 is an orally active A_2A Adenosine receptor antagonist with a K_i of 0.36 nM and a K_B of 1 nM at hA_2AAR. A2AAR antagonist 4 fully inhibits hA_2AAR and hA_2bAR at 10 μM. A2AAR antagonist 4 can be used for research of cancer, such as MC38 tiumor.

A3AR antagonist 3 (compound 21) is a selective A3 adenosine receptor (A3AR) antagonist with a K_i of 37 nM. A3AR antagonist 3 shows >60-fold selectivity in comparison to A1 and A2A adenosine receptors.

ATL444 is a adenosine receptor antagonist, with K_i values of 7.0, 2.5, 61.8, >1000 nM for rA₁AR, rA_2AAR, rA_2BAR, rA₃AR, respectively.

hA2A/hCA XII modulator 1 (compound 14), a triazolopirazine, is a potent hA_2A adenosine receptor (hA_2AAR) antagonist with K_is of 6.4 nM, 4.819 μM, >30 μM for hA_2AAR, hA₁AR, hA₃AR, respectively. hA2A/hCA XII modulator 1 is a potent human carbonic anhydrase XII (hCA XII) inhibitor with K_is of 6.2 nM, 46 nM, 466 nM, 8.351 μM for hCA XII, hCA II, hCA IX and hCA I, respectively. hA2A/hCA XII modulator 1 has the potential for cancer research.

Adenosine receptor antagonist 6 is an orally active and selective A_2A adenosine receptor (A_2AAR) antagonist, with a K_i of 19.18 nM. Adenosine receptor antagonist 6 inhibits 5’-N-ethylcarboxamide adenosine (NECA) (HY-103173)-mediated cAMP production (IC₅₀ = 0.089 μM) and immunosuppression, while promoting IL-2 and IFN-γ secretion. Adenosine receptor antagonist 6 abolishes the immunosuppressive effects of adenosine on T-cell activation and cytokine release. Adenosine receptor antagonist 6 inhibits tumor growth in a CT26/MC38 xenograft model. Adenosine receptor antagonist 6 can be used for the study of colon cancer.

A3AR antagonist 1 (compound 17) is a potent and selective human A₃ adenosine receptor (AR) antagonist, with an K_i of 4.63 nM. A3AR antagonist 1 shows no affinity for the rat A₃ AR even at high concentrations.

A3AR antagonist-7 is a conjugable human A3 adenosine receptor (A3AR) antagonist with a K_i value of 31.8 nM. A3AR antagonist-7 is applicable to the research of melanoma, breast cancer and colorectal cancer.