Bitopertin

Summary

Bitopertin (CHEMBL1171829) is a phase-3 clinical-stage small molecule targeting SLC6A9 and SLC6A5; indicated across 5 conditions including obsessive-compulsive disorder and beta thalassemia.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 2 (SLC6A9, SLC6A5)
• Indications: 5 conditions
• Clinical trials: 29
• Chemistry: 543.5 Da · C21H20F7N3O4S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1171829
Name	Bitopertin
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	24946690
Molecular formula	C21H20F7N3O4S
Molecular weight	543.5
InChIKey	YUUGYIUSCYNSQR-LBPRGKRZSA-N

SMILES: C[C@@H](C(F)(F)F)OC1=C(C=C(C=C1)S(=O)(=O)C)C(=O)N2CCN(CC2)C3=C(C=C(C=N3)C(F)(F)F)F

IUPAC name: [4-[3-fluoro-5-(trifluoromethyl)-2-pyridinyl]piperazin-1-yl]-[5-methylsulfonyl-2-[(2S)-1,1,1-trifluoropropan-2-yl]oxyphenyl]methanone

Also known as: Bitopertin, Bitopertina, Bitopertine, DISC-1459, Paliflutine, R-1678, RG-1678, RO-4917838, RO-4917939, RO4917838, BITOPERTIN, bitopertin

Patent coverage: 128 distinct patent families (334 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 249 (75%) 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
SLC6A9	GlyT1	Inhibition	7.33	0.7%	P48067
SLC6A5	GlyT2	Inhibition	4.52		Q9Y345

Broader ChEMBL bioactivity targets: 1 (assay-derived). Sample: Sodium- and chloride-dependent glycine transporter 1.

Bioactivity

ChEMBL activities: 1 potent at pChembl ≥ 5 of 1 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
SLC6A9	7.33	Ki	47	nM	CHEMBL_ACT_18409278

Target pathways

Aggregated over 2 target gene(s): SLC6A9, SLC6A5.

Top Reactome pathways

8 total, by targets touching each:

Pathway	Targets	Genes
Transport of small molecules	2	SLC6A5, SLC6A9
R-HSA-425366	2	SLC6A5, SLC6A9
SLC-mediated transmembrane transport	2	SLC6A5, SLC6A9
SLC-mediated transport of neurotransmitters	2	SLC6A5, SLC6A9
Disease	1	SLC6A5
Defective SLC6A5 causes hyperekplexia 3 (HKPX3)	1	SLC6A5
SLC transporter disorders	1	SLC6A5
Disorders of transmembrane transporters	1	SLC6A5

Dominant GO biological processes

GO term	Targets
sodium ion transmembrane transport	2
glycine import across plasma membrane	2
neurotransmitter transport	2
neurotransmitter uptake	1
glycine transport	1
positive regulation of hemoglobin biosynthetic process	1
regulation of synaptic transmission, glycinergic	1
glycine secretion, neurotransmission	1
positive regulation of heme biosynthetic process	1
transport across blood-brain barrier	1
amino acid transmembrane transport	1
amino acid transport	1
transmembrane transport	1
chemical synaptic transmission	1
synaptic transmission, glycinergic	1

Indications & clinical

Indications

5 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
obsessive-compulsive disorder	2	MONDO:0008114	EFO:0004242
beta thalassemia	2	MONDO:0019402	Orphanet:848
erythropoietic protoporphyria	2	MONDO:0001676	MONDO:0001676
Diamond-Blackfan anemia	1	MONDO:0015253	MONDO:0015253

1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 29.

Phase distribution

Phase	Trials
PHASE1	14
PHASE3	7
PHASE2	5
PHASE2/PHASE3	1
PHASE1/PHASE2	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05883748	PHASE2/PHASE3	ENROLLING_BY_INVITATION	HELIOS: Open-Label, Long-Term Extension Study to Investigate the Safety, Tolerability, and Efficacy of DISC-1459 (Bitopertin) in Participants With EPP or XLP
NCT06910358	PHASE3	ACTIVE_NOT_RECRUITING	Study of Bitopertin in Participants With EPP or XLP (APOLLO)
NCT01192867	PHASE3	COMPLETED	A Study of RO4917838 in Participants With Persistent, Predominant Negative Symptoms of Schizophrenia (NN25310)
NCT01192880	PHASE3	COMPLETED	A Study to Evaluate Efficacy and Safety of Bitopertin in Participants With Persistent, Predominant Negative Symptoms of Schizophrenia
NCT01192906	PHASE3	COMPLETED	A Study of RO4917838 (Bitopertin) in Patients With Persistent, Predominant Negative Symptoms of Schizophrenia (WN25309)
NCT01235520	PHASE3	COMPLETED	A Study of RO4917838 in Patients With Sub-optimally Controlled Symptoms of Schizophrenia (NN25307)
NCT01235559	PHASE3	COMPLETED	A Study of RO4917838 (Bitopertin) in Patients With Sub-optimally Controlled Symptoms of Schizophrenia (WN25305)
NCT01235585	PHASE3	COMPLETED	A Study of RO4917838 (Bitopertin) in Patients With Sub-optimally Controlled Symptoms of Schizophrenia (WN25306)
NCT00616798	PHASE2	COMPLETED	A Study of RO4917838 in Combination With Antipsychotic Treatment in Patients With Schizophrenia.
NCT01234779	PHASE2	COMPLETED	A Study of RO4917838 (Bitopertin) in Patients With Acute Exacerbation of Schizophrenia
NCT01674361	PHASE2	COMPLETED	A Study of Bitopertin (RO4917838) in Combination With Selective Serotonin Reuptake Inhibitors (SSRIs) in Participants With Obsessive-Compulsive Disorder (OCD)
NCT03271541	PHASE2	COMPLETED	A Study of Bitopertin (RO4917838) in Adults With Non-Transfusion-Dependent (NTD) Beta-Thalassemia
NCT05308472	PHASE2	COMPLETED	Study of Bitopertin to Evaluate the Safety, Tolerability, Efficacy, and PPIX Concentrations in Participants With EPP
NCT05828108	PHASE1/PHASE2	COMPLETED	Study of the Selective GlyT1 Inhibitor Bitopertin for Steroid-Refractory Diamond-Blackfan Anemia
NCT01116830	PHASE1	COMPLETED	A Study of the Effect of RO4917838 on Biomarker Measures of Cognitive Dysfunction in Participants With Schizophrenia and Schizoaffective Disorder
NCT01183585	PHASE1	COMPLETED	A Study of RO4917838 With Rosuvastatin in Healthy Volunteers
NCT01356550	PHASE1	COMPLETED	A Study on The Effect of Hepatic Impairment on The Pharmacokinetics of RO4917838
NCT01365403	PHASE1	COMPLETED	A Study on The Effect of Multiple Dose Carbamazepine on Single Dose Pharmacokinetics of RO4917838 in Healthy Volunteers
NCT01433575	PHASE1	COMPLETED	A Pharmacokinetic Study of RO4917838 in Healthy Chinese Volunteers
NCT01438749	PHASE1	COMPLETED	A Study of The Abuse Liability Potential of RO4917838 in Recreational Drug Users
NCT01495104	PHASE1	COMPLETED	A Study on the Effects of Valproate on the Pharmacokinetics of RO4917838 in Healthy Volunteers
NCT01510899	PHASE1	COMPLETED	A Study on the Effect of Renal Impairment on the Pharmacokinetics of RO4917838
NCT01543529	PHASE1	COMPLETED	A Pharmacodynamic and Pharmacokinetic Study of RO4917838 in Healthy Volunteers
NCT01613040	PHASE1	COMPLETED	A Study of the Effect of RO4917838 on the QTcF Interval in Healthy Volunteers
NCT01636492	PHASE1	COMPLETED	A Study of Bitopertin (RO4917838) in Healthy Male Volunteers
NCT01665976	PHASE1	COMPLETED	A Study of the Relative Bioavailability of Single Dose RO4917838 and the Effect of Food in Healthy Volunteers
NCT02019290	PHASE1	WITHDRAWN	A Study Exmining the Effect of Multiple Doses of Bitopertin on the Single Dose Pharmacokinetics of Midazolam in Healthy Volunteers.
NCT07123363	PHASE1	WITHDRAWN	Effect of Bitopertin on the Liver and on Levels of Protoporphyrin IX in Bile, Blood, Liver, and Stool in Patients With Erythropoietic Protoporphyria/X-linked Protoporphyria and Increased Liver Stiffness and/or Liver Enzymes at Baseline
NCT07603401	Not specified	TEMPORARILY_NOT_AVAILABLE	Expanded Access Program of Bitopertin For Participants With EPP or XLP

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.

5 molecules share ≥1 primary target. Top 5 by shared-target count:

Molecule	Source	Status	Shared targets
GLYCINE	ChEMBL	Phase 4 (approved)	SLC6A9
ICLEPERTIN	ChEMBL	Phase 3	SLC6A9
ORG-25935	ChEMBL	Phase 2	SLC6A9
PF-03463275	ChEMBL	Phase 2	SLC6A9
SARCOSINE	ChEMBL	Phase 2	SLC6A9