Table 3 Small molecule inhibitors and biologics used to target P2 receptors

Suramin

P2X7/P2Y11 receptor orthosteric site

Binding to orthosteric site to compete ATP mediated P2X7 activation

In the clinic, Phase 3 (completed), Phase 2 (completed)

African sleeping sickness, Stage IV prostate cancer, Stage IIIB-IV breast cancer

[131]

NF279 (Suramin analog)

P2X7 receptor orthosteric site

Binding to orthosteric site to compete ATP mediated P2X7 activation

Preclinical

Not available (N/A)

[132]

2, 3-dialdehyde ATP (oxidized ATP)

P2X7 receptor orthosteric site

Binding to orthosteric site to compete ATP mediated P2X7 activation

Preclinical

N/A

[125, 133, 134]

Brilliant Blue G (BBG)

P2X7 receptor inter-subunit allosteric pocket

Binding to the inter-subunit allosteric pocket preventing ATP induced rotation of each subunit and closure of the turret

Preclinical

N/A

[135]

AZ-11645373

P2X7 receptor inter-subunit allosteric pocket

Binding to the inter-subunit allosteric pocket preventing ATP induced rotation of each subunit and closure of the turret

Preclinical

N/A

[136, 137]

JNJ-47965567

P2X7 receptor inter-subunit allosteric pocket

Binding to the inter-subunit allosteric pocket preventing ATP induced rotation of each subunit and closure of the turret

Preclinical

N/A

[138, 139]

CE-224,535

non-competitive antagonist of the human P2X7 receptor

Purinergic P2X7 receptor antagonists

Phase 2 (completed)

Rheumatoid arthritis

[140]

AFC-5128

noncompetitive, negative allosteric modulators

Purinergic P2X7 receptor antagonists

Preclinical

N/A

[138, 141]

BIL-010t

E200 peptide in P2X7 extracellular domain

Polyclonal antibodies with a specific target on epitope (E200) of nonfunctional forms of the P2X7 receptor to block P2X7 activity

Phase 1 (completed)

Basal cell carcinoma (BCC)

[127]

BIL06v

E200 peptide in P2X7 extracellular domain

Peptide-protein conjugate vaccine based on the E200 sequence

Phase 1 (completed)

Solid tumors

[142]

AR-C126313

Selective and competitive P2Y2 receptor antagonist

Inhibited responses mediated by endogenous P2Y2 receptors

Preclinical

N/A

[143]

AR-C118925XX

Selective and competitive P2Y2 receptor antagonist

Iinhibited responses mediated by endogenous P2Y2 receptors

Preclinical

N/A

[144, 145]

Reactive Blue-2

Selective antagonist at P2Y receptors (P2Y2 / P2Y11)

Inhibited responses mediated by endogenous P2Y2 receptors

Preclinical

N/A

[146]

Flavonoid

Selective antagonist at P2Y receptors

Reduce the amplitude of the P2Y2 receptor response to UTP

Phase II/ III

Hematopoietic/lymphoid or solid cancer

[146, 147]

NF157

Highly selective nanomolar P2Y11 antagonist

Competitive antagonism against ATP

Preclinical

N/A

[148, 149]

NF340

Highly selective nanomolar P2Y11 antagonist

Competitive antagonism against ATP

Preclinical

N/A

[148]