Tofogliflozin Anhydrous
drug drugOn this page
Also known as CSG-452R-7201RO-4998452RO4998452TofoglifozinTOFOGLIFLOZIN (HYDRATE)TOFOGLIFLOZIN
Summary
Tofogliflozin Anhydrous (CHEMBL2110731) is an approved small molecule targeting SLC5A1 and SLC5A2.
At a glance
- Status: Approved (max clinical phase 4)
- Modality: Small molecule
- Targets: 2 (SLC5A1, SLC5A2)
- Clinical trials: 8
- Chemistry: 386.4 Da · C22H26O6
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL2110731 |
| Name | Tofogliflozin Anhydrous |
| Type | Small molecule |
| Max phase | 4 |
| FDA approved | no |
| PubChem CID | 46908929 |
| Molecular formula | C22H26O6 |
| Molecular weight | 386.4 |
| InChIKey | VWVKUNOPTJGDOB-BDHVOXNPSA-N |
SMILES: CCC1=CC=C(C=C1)CC2=CC3=C(CO[C@@]34[C@@H]([C@H]([C@@H]([C@H](O4)CO)O)O)O)C=C2
IUPAC name: (3S,3’R,4’S,5’S,6’R)-5-[(4-ethylphenyl)methyl]-6’-(hydroxymethyl)spiro[1H-2-benzofuran-3,2’-oxane]-3’,4’,5’-triol
Also known as: CSG-452, R-7201, RO-4998452, RO4998452, Tofogliflozin anhydrous, Tofoglifozin, TOFOGLIFLOZIN (HYDRATE), TOFOGLIFLOZIN, Tofogliflozin (hydrate)
Parent form; salt/anhydrous children: CHEMBL2105711
Patent coverage: 594 distinct patent families (1,556 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 1,488 (96%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.
Targets
Targets
Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).
| Gene | Target | Action | pAffinity | Cancer dependency | UniProt |
|---|---|---|---|---|---|
| SLC5A1 | Sodium/glucose cotransporter 1 | Inhibition | 5.07 | 0% | P13866 |
| SLC5A2 | Sodium/glucose cotransporter 2 | Inhibition | 8.54 | 0.2% | P31639 |
Broader ChEMBL bioactivity targets: 2 (assay-derived). Sample: Sodium/glucose cotransporter 2, Sodium/glucose cotransporter 1.
Bioactivity
ChEMBL activities: 5 potent at pChembl ≥ 5 of 5 total. Top 100 by potency (10 = 0.1 nM, 6 = 1 µM):
| Target | pChembl | Type | Value | Unit | Activity ID |
|---|---|---|---|---|---|
| SLC5A2 | 8.54 | IC50 | 2.9 | nM | CHEMBL_ACT_12109343 |
| SLC5A2 | 8.54 | IC50 | 2.9 | nM | CHEMBL_ACT_19001168 |
| SLC5A2 | 8.4 | IC50 | 4 | nM | CHEMBL_ACT_18665715 |
| SLC5A1 | 5.07 | IC50 | 8444 | nM | CHEMBL_ACT_12109323 |
| SLC5A1 | 5.07 | IC50 | 8444 | nM | CHEMBL_ACT_19001159 |
Target pathways
Aggregated over 2 target gene(s): SLC5A1, SLC5A2.
Top Reactome pathways
11 total, by targets touching each:
| Pathway | Targets | Genes |
|---|---|---|
| Disease | 2 | SLC5A1, SLC5A2 |
| Cellular hexose transport | 2 | SLC5A1, SLC5A2 |
| Transport of small molecules | 2 | SLC5A1, SLC5A2 |
| SLC-mediated transmembrane transport | 2 | SLC5A1, SLC5A2 |
| SLC transporter disorders | 2 | SLC5A1, SLC5A2 |
| Disorders of transmembrane transporters | 2 | SLC5A1, SLC5A2 |
| Defective SLC5A1 causes congenital glucose/galactose malabsorption (GGM) | 1 | SLC5A1 |
| Defective SLC5A2 causes renal glucosuria (GLYS1) | 1 | SLC5A2 |
| Intestinal absorption | 1 | SLC5A1 |
| Digestion and absorption | 1 | SLC5A1 |
| Intestinal hexose absorption | 1 | SLC5A1 |
Dominant GO biological processes
| GO term | Targets |
|---|---|
| alpha-glucoside transport | 2 |
| sodium ion transport | 2 |
| renal D-glucose absorption | 2 |
| D-glucose import across plasma membrane | 2 |
| sodium ion import across plasma membrane | 2 |
| D-glucose transmembrane transport | 2 |
| monoatomic ion transport | 2 |
| transmembrane transport | 2 |
| intestinal D-glucose absorption | 1 |
| pentose transmembrane transport | 1 |
| fucose transmembrane transport | 1 |
| galactose transmembrane transport | 1 |
| myo-inositol transport | 1 |
| transepithelial water transport | 1 |
| intestinal hexose absorption | 1 |
Indications & clinical
Indications
0 indication records carry no mapped disease name (EFO/MeSH-only); none shown.
Clinical trials
Total trials: 8.
Phase distribution
| Phase | Trials |
|---|---|
| PHASE4 | 3 |
| PHASE1 | 3 |
| PHASE2 | 2 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT02201004 | PHASE4 | COMPLETED | TOFO Insulin Combination Trial |
| NCT02537834 | PHASE4 | COMPLETED | Tofogliflozin GLP-1 Analogue Combination Trial |
| NCT02649465 | PHASE4 | COMPLETED | SGLT2 Inhibitor Versus Sulfonylurea on Type 2 Diabetes With NAFLD |
| NCT05469659 | PHASE2 | RECRUITING | Effect of Tofogliflozin on UACR Compared to Metformin Hydrochloride in Diabetic Kidney Disease (TRUTH-DKD) |
| NCT00800176 | PHASE2 | COMPLETED | A Dose-Finding Study of RO4998452 in Patients With Diabetes Mellitus |
| NCT00682097 | PHASE1 | COMPLETED | A Multiple Ascending Dose Study of RO4998452 in Patients With Type 2 Diabetes Mellitus. |
| NCT00933972 | PHASE1 | COMPLETED | A Study of RO4998452 in Type 2 Diabetes Patients With Varying Degrees of Renal Impairment |
| NCT01044017 | PHASE1 | COMPLETED | A Study of Single Doses of RO4998452 in Patients With Type 2 Diabetes |
Clinical evidence (CIViC)
No CIViC predictive evidence (expected for non-precision-medicine drugs).
Pharmacology
Pharmacogenomics
No PharmGKB pharmacogenomic data curated for this drug.
Related molecules
Related molecules
Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.
16 molecules share ≥1 primary target. Top 16 by shared-target count:
| Molecule | Source | Status | Shared targets |
|---|---|---|---|
| BEXAGLIFLOZIN | ChEMBL + PubChem | Phase 4 (approved) | SLC5A1, SLC5A2 |
| Canagliflozin | ChEMBL + PubChem | Phase 4 (approved) | SLC5A1, SLC5A2 |
| EMPAGLIFLOZIN | ChEMBL + PubChem | Phase 4 (approved) | SLC5A1, SLC5A2 |
| ERTUGLIFLOZIN | ChEMBL + PubChem | Phase 4 (approved) | SLC5A1, SLC5A2 |
| SOTAGLIFLOZIN | ChEMBL + PubChem | Phase 4 (approved) | SLC5A1, SLC5A2 |
| DAPAGLIFLOZIN | ChEMBL | Phase 4 (approved) | SLC5A1, SLC5A2 |
| IPRAGLIFLOZIN | ChEMBL | Phase 4 (approved) | SLC5A1, SLC5A2 |
| ENAVOGLIFLOZIN | ChEMBL | Phase 3 | SLC5A1, SLC5A2 |
| HENAGLIFLOZIN | ChEMBL | Phase 3 | SLC5A1, SLC5A2 |
| LICOGLIFLOZIN | ChEMBL | Phase 2 | SLC5A1, SLC5A2 |
| LUSEOGLIFLOZIN | ChEMBL | Phase 2 | SLC5A1, SLC5A2 |
| REMOGLIFLOZIN ETABONATE | ChEMBL | Phase 2 | SLC5A1, SLC5A2 |
| SERGLIFLOZIN ETABONATE | ChEMBL | Phase 2 | SLC5A1, SLC5A2 |
| MIZAGLIFLOZIN | ChEMBL | Phase 2 | SLC5A1 |
| YM-543 FREE ACID | ChEMBL | Phase 2 | SLC5A2 |
| Phlorizin | PubChem | Approved | SLC5A1 |