SPHK2 sphingosine kinase 2
ENSG00000063176 · protein coding · Open Targets profile
Catalyzes the phosphorylation of sphingosine to form sphingosine-1-phosphate (SPP), a lipid mediator with both intra- and extracellular functions. Also acts on D-erythro-dihydrosphingosine, D- erythro-sphingosine and L-threo-dihydrosphingosine. Binds phosphoinositides (PubMed:12954646, PubMed:19168031). In contrast to prosurvival SPHK1, has a positive effect on intracellular ceramide levels, inhibits cells growth and enhances apoptosis (PubMed:16118219). In mitochondria, is important for cytochrome-c oxidase assembly and mitochondrial respiration. The SPP produced in mitochondria binds PHB2 and modulates the regulation via PHB2 of complex IV assembly and respiration (PubMed:20959514). In nucleus, plays a role in epigenetic regulation of gene expression. Interacts with HDAC1 and HDAC2 and, through SPP production, inhibits their enzymatic activity, preventing the removal of acetyl groups from lysine residues with histones. Up- regulates acetylation of histone H3-K9, histone H4-K5 and histone H2B- K12 (PubMed:19729656). In nucleus, may have an inhibitory effect on DNA synthesis and cell cycle (PubMed:12954646, PubMed:16103110). In mast cells, is the main regulator of SPP production which mediates calcium influx, NF-kappa-B activation, cytokine production, such as TNF and IL6, and degranulation of mast cells (By similarity). In dopaminergic neurons, is involved in promoting mitochondrial functions regulating ATP and ROS levels (By similarity). Also involved in the regulation of glucose and lipid metabolism (By similarity). {ECO:0000250|UniProtKB:Q9JIA7, ECO:0000269|PubMed:12954646, ECO:0000269|PubMed:16103110, ECO:0000269|PubMed:16118219, ECO:0000269|PubMed:19168031, ECO:0000269|PubMed:19729656, ECO:0000269|PubMed:20959514}.
Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.
Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.
Tractability
- Small molecule
- Advanced Clinical, High-Quality Ligand
- PROTAC
- Half-life Data, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.5576000213623047 (upper bound 0.8268499970436096). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.
Who runs trials of these drugs
Principal investigators and study chairs on 4 registry trials, updated in the last three years, of the most advanced drugs against SPHK2 (ABC-294640), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Mark L LevittRedHill Biopharma Limited · 1 of 1 trials Phase 2+
- Michael LillyMedical University of South Carolina · 1 of 1 trials Phase 2+
- Micheal LillyMedical University of South Carolina · 1 of 1 trials Phase 2+
- Mitesh BoradMayo Clinic · 1 of 1 trials Phase 2+
Registry trials of ABC-294640 updated in the last three years, counted by the country group of their listed sites. A trial with sites in several groups counts in each; 3 of 4 have all sites in one country.
Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where sites are is a fact about the record, not a judgement of its quality. Europe is the EU and EEA, the UK and Switzerland. Source: ClinicalTrials.gov, fetched live.
3 trials of drugs against SPHK2 were stopped early
Terminated, withdrawn and suspended interventional trials of ABC-294640, newest update first, live from ClinicalTrials.gov. Each reason is quoted exactly as the registry gives it; we do not sort reasons into safety, efficacy or business. Dates are the last registry update. Showing the 3 most recent of 3.
- withdrawn · 2025-04-27 · Medical University of South Carolina · matched by the registry's drug synonyms“study is being rewritten for different disease population”
- terminated · 2021-06-18 · RedHill Biopharma Limited · matched by the registry's drug synonyms“Expiration of National Cancer Institute (NCI) funding of the study.”
- withdrawn · 2017-12-07 · RedHill Biopharma Limited · matched by the registry's drug synonyms“Study was discontinued due to lack of recruitment.”
Paediatric incentives and obligations for SPHK2's drugs
For ABC-294640: what EMA and FDA publish about paediatric plans, orphan status and pediatric approvals, and how many registered studies take children. Each line is a yes, no or not published fact from the record linked under it; none of it is a forecast.
- FDA pediatric target list: no · SPHK2 is not on the listRule: Target is on FDA's Pediatric Molecular Target List (relevant targets). Source: FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01)), 2026-11-11
- EU paediatric investigation plan: no · No EMA paediatric investigation plan decision names abc-294640Rule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA data download (dated snapshot), 2026-11-11
- EU orphan designation: no · No EU orphan designation names abc-294640Rule: An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status. Source: EMA data download (dated snapshot), 2026-11-11
- Authorised in the EU: no · EMA lists no centrally authorised medicine of abc-294640Rule: An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file. Source: EMA data download (dated snapshot), 2026-11-11
- FDA orphan designation: not published · FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the linkRule: Would be: an FDA orphan designation names the drug. Source: FDA orphan designations search
- FDA pediatric oncology approval: no · FDA's table lists no pediatric approval of abc-294640Rule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-11
- Registered studies open to children: no · No interventional study of abc-294640 includes patients under 18Rule: The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age. Source: ClinicalTrials.gov search, 2026-11-11
Rare pediatric disease voucher. FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs
All 1 drugs and clinical candidates as a table
Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.
| Drug | Type | Highest stage | Indications | Source records |
|---|---|---|---|---|
| ABC-294640 | Small molecule | phase 3 | pneumonia, cholangiocarcinoma, hepatocellular carcinoma, prostate cancer, plasma cell myeloma, Kaposi's sarcoma, diffuse large B-cell lymphoma, COVID-19 | Open Targets · ChEMBL |