| Topic | Key points | Quantitative / implementation details | Source (date; DOI URL) |
|---|---|---|---|
| Identity / verified target | Human **FZD7 / Frizzled-7**; **class F GPCR** (Frizzled family); extracellular **CRD**, linker, **7TM** core, intracellular C-tail that recruits **DVL**; plasma-membrane receptor; family often includes a **PDZ-binding motif** in the C-tail (family-level feature) (pqac-00000001, pqac-00000003, pqac-00000004) | Inactive human FZD7 structure solved; receptor studied as membrane WNT receptor coupled mainly to DVL-centered signaling (pqac-00000001, pqac-00000003) | **Aug 2024** Nature Communications; https://doi.org/10.1038/s41467-024-51664-4 (pqac-00000001) ; **May 2025** Front Cell Dev Biol; https://doi.org/10.3389/fcell.2025.1599355 (pqac-00000003) |
| Mechanism 2023: pathway selectivity | Conserved micro-switch **R/K6.32-W7.55** helps define active conformations; Frizzleds generally **prefer DVL over heterotrimeric G proteins**; conformational states determine pathway output (pqac-00000005, pqac-00000006) | 32 alanine mutants tested in FZD5; principles extended to FZD4/FZD10 and likely informative for FZD7 (pqac-00000005) | **Jul 2023** Nature Communications; https://doi.org/10.1038/s41467-023-40213-0 (pqac-00000005) |
| Mechanism 2024: FZD7 structure | Apo/inactive human FZD7 cryo-EM structure identifies **internal water pocket**, **lipid interactions**, and conserved **cholesterol-binding site** important for **DVL association** and downstream signalosome formation (pqac-00000001, pqac-00000002, pqac-00000014) | **1.9 Å** cryo-EM resolution; cholesterol-site residues highlighted include **F2.46, F3.34/F3.35, W4.50, H4.46**; water-pocket bottleneck includes **D405, L415, Y489, K533, Y534** (pqac-00000001, pqac-00000002, pqac-00000014) | **Aug 2024** Nature Communications; https://doi.org/10.1038/s41467-024-51664-4 (pqac-00000001) |
| Mechanistic figure support | Structural figure shows conserved FZD7 cholesterol pocket and bound cholesterol in cryo-EM density (pqac-00000014) | Figure 6 annotates conserved site and bound cholesterol (pqac-00000014) | **Aug 2024** Nature Communications figure context; https://doi.org/10.1038/s41467-024-51664-4 (pqac-00000014) |
| Trafficking / receptor abundance | **RNF43** and **ZNRF3** ubiquitinate FZD receptors to drive endocytosis/lysosomal degradation; **RNF43 preferentially down-regulates FZD1/FZD5/FZD7**, whereas **ZNRF3 prefers FZD6** (pqac-00000008) | Negative-feedback WNT target genes; receptor-specific TMD determinants explain selectivity; suggests FZD7 vulnerability in RNF43-mutant cancers (pqac-00000008) | **Jul 2024** Life Science Alliance; https://doi.org/10.26508/lsa.202402575 (pqac-00000008) |
| Cancer-context trafficking statistic | Review summarizes that defects in turnover genes such as **RNF43** can cause **FZD7 surface accumulation** in **~54%** of patients in relevant cancer settings (pqac-00000009) | ~54% value reported in review summary; useful as translational prevalence estimate, but primary cohort details should be checked in cited source (pqac-00000009) | **May 2025** Sci; https://doi.org/10.3390/sci7020061 (pqac-00000009) |
| Small-molecule / CRD-directed targeting | Structure-guided inhibition includes **SRI37892** (TMD-targeting FZD7 inhibitor) and CRD binders; docking identified **30 FZD7-CRD binders**, including **Zinc05972969** (pqac-00000011) | Breast-cancer growth inhibitor reported **IC50 ~2 µM**; Zinc05972969 binding free energy **-8.1 kcal/mol** with H-bonds to **Lys61/Gln55**; comparator feasibility example: carbamazepine-FZD8 **KD 17 µM**, inhibitory conc. **~8 µM** (pqac-00000011) | **Apr 2024** Acta Pharmacol Sin; https://doi.org/10.1038/s41401-024-01270-3 (pqac-00000011) |
| Biologics / decoys / ADCs / nanoparticles | Reviews list **OMP-18R5/Vantictumab** (pan-FZD incl. FZD7), **FZD7 scFv antibodies**, **soluble recombinant FZD7 / FZD-Fc decoys**, **FZD7-ADCs**, **FZD7-targeted nanoparticles**, peptide inhibitors, siRNA/miRNA approaches (pqac-00000009, pqac-00000013) | Implementations include doxorubicin or **β-catenin siRNA** nanoparticle delivery; OMP-18R5 reduced gastric-cancer spheroid formation; FZD7-ADC designed for tumor-selective cytotoxicity (pqac-00000009, pqac-00000013) | **May 2025** Sci; https://doi.org/10.3390/sci7020061 (pqac-00000009) ; **May 2025** Front Cell Dev Biol; https://doi.org/10.3389/fcell.2025.1599355 (pqac-00000013) |
| Immune engager | **SHH002-hu1-MICA**: FZD7-targeting bifunctional protein retargeting **NK cells** to TNBC/TNBC stem-like cells via **MICA-NKG2D** axis (pqac-00000012) | Binds **rhFzd7** and **rhNKG2D** (BLI/SPR), disrupts Wnt/β-catenin signaling, increases NK degranulation/infiltration, outperforms parental antibody in xenografts (pqac-00000012) | **Feb 2025** J Immunother Cancer; https://doi.org/10.1136/jitc-2024-009621 (pqac-00000012) |


*Table: This table condenses verified human FZD7 identity, recent mechanistic findings, trafficking regulation, therapeutic strategies, and key quantitative values from the cited evidence. It is useful as a quick-reference scaffold for the full functional annotation report.*