Diphenidol

Summary

Diphenidol (CHEMBL936) is an approved small-molecule antiemetic targeting TAS2R13 and TAS2R20.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• Targets: 2 (TAS2R13, TAS2R20)
• Chemistry: 309.4 Da · C21H27NO

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL936
Name	Diphenidol
Type	Small molecule
Max phase	4
FDA approved	no
PubChem CID	3055
ChEBI	CHEBI:4638
Molecular formula	C21H27NO
Molecular weight	309.4
InChIKey	OGAKLTJNUQRZJU-UHFFFAOYSA-N

SMILES: C1CCN(CC1)CCCC(C2=CC=CC=C2)(C3=CC=CC=C3)O

IUPAC name: 1,1-diphenyl-4-piperidin-1-ylbutan-1-ol

ChEBI definition: A tertiary alcohol that is butan-1-ol substituted by two phenyl groups at position 1 and a piperidin-1-yl group at position 4.

Pharmacological roles (ChEBI): antiemetic.

Also known as: Difenidol, Difenidol hydrochloride, Diphenidol, SK&F 478, SK&F-478, SK-478, Vontrol, SID11112531, SID50100475, DIPHENIDOL, SID144206624, SID170465280

Parent form; salt/anhydrous children: CHEMBL1529, CHEMBL2105784

Patent coverage: 1,491 distinct patent families (5,514 SureChEMBL compound mentions), from 1 matched compound structure(s). 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
TAS2R13	TAS2R13	Agonist		0%	Q9NYV9
TAS2R20	TAS2R20	Agonist		0.1%	P59543

Broader ChEMBL bioactivity targets: 17 (assay-derived). Sample: Lysine-specific demethylase 4E, Muscarinic acetylcholine receptor M4, Muscarinic acetylcholine receptor M5, D(1A) dopamine receptor, Sodium channel alpha subunits; brain (Types I, II, III), Muscarinic acetylcholine receptor M2, 5-hydroxytryptamine receptor 1A, Muscarinic acetylcholine receptor M1, D(2) dopamine receptor, 5-hydroxytryptamine receptor 2A.

Bioactivity

ChEMBL activities: 29 potent at pChembl ≥ 5 of 33 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
CHRM4	7.42	Ki	38	nM	CHEMBL_ACT_7685720
CHRM3	7.28	Ki	52	nM	CHEMBL_ACT_7685718
CHRM1	7.11	Ki	78	nM	CHEMBL_ACT_7685714
SIGMAR1	6.97	Ki	108	nM	CHEMBL_ACT_7685810
CYP2D6	6.9	Potency	125.9	nM	CHEMBL_ACT_4986128
CYP2D6	6.9	AC50	125.9	nM	CHEMBL_ACT_6019628
CHRM3	6.61	IC50	245	nM	CHEMBL_ACT_7685717
SIGMAR1	6.59	IC50	256	nM	CHEMBL_ACT_7685809
CHRM4	6.57	IC50	271	nM	CHEMBL_ACT_7685719
CHRM2	6.56	Ki	274	nM	CHEMBL_ACT_7685716
CYP2D6	6.49	IC50	326.3	nM	CHEMBL_ACT_7683633
CHRM1	6.49	IC50	324	nM	CHEMBL_ACT_7685713
CHRM2	6.42	AC50	380	nM	CHEMBL_ACT_25196378
CHRM1	6.28	AC50	525.1	nM	CHEMBL_ACT_25210197
HTR2A	6.13	Ki	739	nM	CHEMBL_ACT_7685796
DRD3	6.11	Ki	785	nM	CHEMBL_ACT_7683644
CHRM2	6.11	IC50	770	nM	CHEMBL_ACT_7685715
CHRM5	6.07	Ki	855	nM	CHEMBL_ACT_7685722
CHRM2	6.03	AC50	943.7	nM	CHEMBL_ACT_25195718
DRD2	5.96	Ki	1097	nM	CHEMBL_ACT_7683642
CHRM5	5.92	IC50	1191	nM	CHEMBL_ACT_7685721
DRD3	5.67	AC50	2151	nM	CHEMBL_ACT_25194505
DRD3	5.64	IC50	2311	nM	CHEMBL_ACT_7683643
HTR2A	5.59	IC50	2586	nM	CHEMBL_ACT_7685795
P15823	5.58	Ki	2635	nM	CHEMBL_ACT_7683568
DRD2	5.48	IC50	3290	nM	CHEMBL_ACT_7683641
SCN1A	5.47	IC50	3400	nM	CHEMBL_ACT_352494
P15823	5.32	IC50	4760	nM	CHEMBL_ACT_7683567
HTR1A	5.16	AC50	6873	nM	CHEMBL_ACT_25165006

Target pathways

Aggregated over 2 target gene(s): TAS2R13, TAS2R20.

Top Reactome pathways

9 total, by targets touching each:

Pathway	Targets	Genes
Signal Transduction	2	TAS2R13, TAS2R20
Signaling by GPCR	2	TAS2R13, TAS2R20
GPCR downstream signalling	2	TAS2R13, TAS2R20
G alpha (i) signalling events	2	TAS2R13, TAS2R20
Class C/3 (Metabotropic glutamate/pheromone receptors)	2	TAS2R13, TAS2R20
GPCR ligand binding	2	TAS2R13, TAS2R20
Sensory Perception	2	TAS2R13, TAS2R20
Sensory perception of taste	2	TAS2R13, TAS2R20
Sensory perception of sweet, bitter, and umami (glutamate) taste	2	TAS2R13, TAS2R20

Dominant GO biological processes

GO term	Targets
detection of chemical stimulus involved in sensory perception of bitter taste	2
signal transduction	2
G protein-coupled receptor signaling pathway	2
sensory perception of taste	2
positive regulation of cytokinesis	1

Indications & clinical

Indications

0 indications (0 at ChEMBL trial phase 4).

Clinical trials

Total trials: 0.

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

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.

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

Molecule	Source	Status	Shared targets
ISOPROTERENOL	ChEMBL	Phase 4 (approved)	TAS2R13, TAS2R20