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A single-cell RNA-Seq (scRNA-Seq) study analyzed primary NP and AF cells isolated from healthy adult discs and observed that receptor signaling pathway genes were highly expressed in the AF, whereas protein synthesis and ECM genes were highly expressed in the NP (Fernandes et al., 2020)

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Among those, the tyrosine derivative 28 exhibited a Ki value of 4.1 nM and the corresponding analogue with a saturated double bond, compound 29 , a Ki value of 25 nM, demonstrating that a proper constrain of flexibility of the ring system, alternatively an electron density in the center of the lipophilic bridge between amino acid residues in positions 1 and 3 is favorable for affinity to IRAP (Figure 7)