S1PR1 as a Radioligand Therapy Target
S1PR1, sphingosine-1-phosphate receptor 1, is a cell-surface protein (GPCR). In Human Protein Atlas immunohistochemistry, S1PR1 staining is highest in glioma (100% of samples positive), thyroid cancer (100% of samples positive) and endometrial cancer (100% of samples positive). Published literature reports that S1PR1 internalizes after ligand binding, which helps retain a radionuclide inside tumor cells. Clinical status: Clinical-stage (up to phase 3, any modality).
Is S1PR1 a good radioligand therapy target?
Scored against the six criteria that decide whether a protein can become a radioligand therapy:
- ✅ Cell-surface accessibility: Localized to the cell surface, so a radioligand can reach it from circulation.
- ✅ Tumor expression: High IHC staining in glioma, 100% of samples positive.
- ✅ Internalization: Reported to internalize, which favors radionuclide retention.
- ✅ Clinical precedent: Clinical-stage (up to phase 3, any modality)
- ❔ Shedding: Not yet assessed.
- ❔ Normal-tissue dosimetry: Check kidney, liver, bone marrow and salivary expression in the Human Protein Atlas tissue atlas.
S1PR1 expression in cancer
Protein expression of S1PR1 across 20 cancer types from Human Protein Atlas immunohistochemistry. The score is a weighted staining intensity from 0 to 1; "% positive" is the share of patient samples with detectable staining.
| Cancer type | IHC score | Level | % positive |
|---|---|---|---|
| Glioma | 0.86 | High | 100% |
| Thyroid Cancer | 0.83 | High | 100% |
| Endometrial Cancer | 0.79 | High | 100% |
| Melanoma | 0.69 | High | 100% |
| Head and Neck Cancer | 0.67 | High | 100% |
| Ovarian Cancer | 0.61 | High | 100% |
| Cervical Cancer | 0.61 | High | 100% |
| Liver Cancer | 0.61 | High | 100% |
| Skin Cancer | 0.58 | High | 100% |
| Lymphoma | 0.58 | High | 92% |
| Bladder Cancer | 0.58 | High | 82% |
| Breast Cancer | 0.56 | High | 83% |
| Kidney Cancer | 0.53 | High | 83% |
| Lung Cancer | 0.52 | High | 82% |
| Testicular Cancer | 0.48 | Medium | 100% |
| Colorectal Cancer | 0.47 | Medium | 100% |
| Pancreatic Cancer | 0.42 | Medium | 83% |
| Neuroendocrine Tumors | 0.42 | Medium | 75% |
| Gastric Cancer | 0.39 | Medium | 73% |
| Prostate Cancer | 0.33 | Medium | 82% |
Is S1PR1 internalized?
Yes. S1P-bound S1PR1 forms a complex with Dll4 via the scaffolding protein MPDZ, and undergoes co-endocytosis.
Sources: PMID 42239339 · PMID 42135812 · PMID 41996212 · PMID 41824554 · PMID 41127406. AI-extracted from abstracts, so verify before citing.
S1PR1 clinical trials
Clinical-stage (up to phase 3, any modality). Nuclens hasn't indexed trials for S1PR1 yet. Search ClinicalTrials.gov for S1PR1 trials.
S1PR1 normal tissue expression
Normal-tissue expression in dose-limiting organs (kidney, liver, bone marrow, salivary glands) drives radioligand dosimetry risk. Nuclens is re-validating its normal-tissue values, so they are not shown here yet. See S1PR1 in the Human Protein Atlas tissue atlas, and read how normal-tissue expression predicts radioligand dosimetry risk.
S1PR1 gene essentiality (DepMap)
CRISPR knockout effect across 1255 cancer cell lines: 0.00 (not essential). Radioligands kill by radiation, not by blocking the target, so essentiality matters less than for inhibitors. A non-essential target can still be an excellent radioligand target.
Related glioma radioligand targets
EGFR · HER3 (ERBB3) · c-MET (MET) · ITGAV · B7-H3 (CD276) · SSTR2 · STEAP2 · FAP
See all radioligand therapy targets in glioma.
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Subcellular localization: UniProt via Open Targets (CC BY 4.0 / CC0). Tumor immunohistochemistry: Human Protein Atlas (CC BY-SA 4.0). Clinical trials: ClinicalTrials.gov (public domain). Gene essentiality: DepMap (CC BY 4.0). Internalization and shedding: AI-extracted from PubMed abstracts, so verify against the cited papers before relying on them. Nuclens is a first-pass triage layer, not a substitute for wet-lab validation or clinical dosimetry. Derived expression data on this page is shared under CC BY-SA 4.0.