**Background**
Prokineticin 2 (PK2) is a potent secreted protein that plays a critical role in regulating angiogenesis, inflammation, and cell migration through its interaction with G protein-coupled receptors, specifically PKR1 and PKR2. Overexpression of PK2 and its receptors is often associated with the progression of various malignancies and inflammatory diseases, making the PK2 signaling pathway an attractive target for therapeutic intervention. In particular, the inhibition of PK2-mediated angiogenesis and myeloid cell infiltration can suppress tumorigenic processes in several types of cancer. Therefore, in this context, we will introduce a potent prokineticin 2 antagonist – PKRA83.
**Definition**
PKRA83 (also known as PKRA7) is a potent prokineticin 2 antagonist that competes for the binding of PK2 to its receptors PKR1 and PKR2. According to the PKRA83 description, it potently inhibits these receptors with IC50 values of 5.0 nM for PKR1 and 8.2 nM for PKR2.
**In Vitro and In Vivo Studies**
The PKRA83 biological activity has been demonstrated across various experimental models, showing significant anticancer, anti-arthritis, and anti-angiogenic properties. In terms of PKRA83 in vitro data, treatment with 1 µg/mL of PKRA83 effectively reduces PK2-induced microvascular endothelial cell branching. Additionally, PKRA83 (2 μM, 24 h) has been shown to block the neuroprotective action of rPK2 in dopaminergic N27 cells, specifically preventing rPK2 from protecting these cells against MPP+-induced neuronal cell death.
Regarding PKRA83 In Vivo efficacy, the compound exhibits strong anti-tumor activity in glioblastoma xenograft tumor models (D456MG glioma cell nu/nu mouse). Administration of 20 mg/kg via i.p. daily resulted in a decreased tumor growth rate and tumor weight, alongside increased necrotic regions and decreased relative blood vessel density within the tumors. Furthermore, in mice with collagen-induced arthritis, daily i.p. administration of 15 mg/kg for 2 weeks inhibited arthritis, as evidenced by reduced synovial thickening, less extensive inflammatory cell infiltration in joints, and lowered gene expression levels of IL-1β and IL-6. In conclusion, PKRA83 is a potent PKR1/PKR2 antagonist with broad potential for treating cancer and inflammatory disorders.
Keywords
PKRA83, 1233926-87-8, PKRA7, PKRA 83, PKRA-83, PKRA 7, PKRA-7, Prokineticin Receptor, prokineticin, PKR1, PKR2, anticancer, anti-angiogenic activities, blood-brain barrier, arthritis
References
[1] Valerie F Curtis, et al. A PK2/Bv8/PROK2 antagonist suppresses tumorigenic processes by inhibiting angiogenesis in glioma and blocking myeloid cell infiltration in pancreatic cancer. PLoS One. 2013;8(1):e54916.
[2] Ito H, et al. Prokineticin 2 antagonist, PKRA7 suppresses arthritis in mice with collagen-induced arthritis. BMC Musculoskelet Disord. 2016 Sep 8;17(1):387.
[3] Gordon R, et al. Prokineticin-2 upregulation during neuronal injury mediates a compensatory protective response against dopaminergic neuronal degeneration. Nat Commun. 2016 Oct 5;7:12932.