Carbenoxolone

Summary

Carbenoxolone (CHEMBL499915) is an approved small molecule (ATC A02BX51) targeting GJE1, GJB7, and GJB2; indicated across 2 conditions including gastroesophageal reflux disease and peptic ulcer disease.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: A02BX51 (+2 more)
• Targets: 24 (GJE1, GJB7, GJB2…)
• Indications: 2 conditions
• Chemistry: 570.8 Da · C34H50O7

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL499915
Name	Carbenoxolone
Type	Small molecule
Max phase	4
FDA approved	no
PubChem CID	636403
ATC	A02BX51, A02BX01, A02BX71
Molecular formula	C34H50O7
Molecular weight	570.8
InChIKey	OBZHEBDUNPOCJG-WBXJDKIVSA-N

SMILES: C[C@]12CC[C@](C[C@H]1C3=CC(=O)[C@@H]4[C@]5(CC[C@@H](C([C@@H]5CC[C@]4([C@@]3(CC2)C)C)(C)C)OC(=O)CCC(=O)O)C)(C)C(=O)O

IUPAC name: (2S,4aS,6aR,6aS,6bR,8aR,10S,12aS,14bR)-10-(3-carboxypropanoyloxy)-2,4a,6a,6b,9,9,12a-heptamethyl-13-oxo-3,4,5,6,6a,7,8,8a,10,11,12,14b-dodecahydro-1H-picene-2-carboxylic acid

Also known as: Carbenoxolona, Carbenoxolone, carbenoxolone, CARBENOXOLONE

Parent form; salt/anhydrous children: CHEMBL1697717

Patent coverage: 1,142 distinct patent families (3,947 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
	VRAC
GJE1	Cx23			1.4%	A6NN92
GJB7	Cx25			0%	Q6PEY0
GJB2	Cx26			0.2%	P29033
GJB6	Cx30			0.2%	O95452
GJC3	Cx30.2			2.2%	Q8NFK1
GJB4	Cx30.3			0.4%	Q9NTQ9
GJB3	Cx31			0.5%	O75712
GJB5	Cx31.1			0.1%	O95377
GJD3	Cx31.9			1.6%	Q8N144
GJB1	Cx32			0.1%	P08034
GJD2	Cx36			0%	Q9UKL4
GJA4	Cx37			0.1%	P35212
GJA5	Cx40			1.2%	P36382
GJD4	Cx40.1			0.6%	Q96KN9
GJA1	Cx43			1.6%	P17302
GJC1	Cx45			3.1%	P36383
GJA3	Cx46			18.5%	Q9Y6H8
GJC2	Cx47			0%	Q5T442
GJA8	Cx50			0.4%	P48165
GJA9	Cx59			0.3%	P57773
GJA10	Cx62				Q969M2
PANX1	Px1			0%	Q96RD7
PANX2	Px2			0.2%	Q96RD6
PANX3	Px3			0%	Q96QZ0

Broader ChEMBL bioactivity targets: 14 (assay-derived). Sample: 5-hydroxytryptamine receptor 2B, Alpha-2A adrenergic receptor, Muscarinic acetylcholine receptor M2, 5-hydroxytryptamine receptor 1A, Cannabinoid receptor 1, 5-hydroxytryptamine receptor 2A, Alpha-1A adrenergic receptor, 3’,5’-cyclic-AMP phosphodiesterase 4D, Tyrosine-protein phosphatase non-receptor type 1, 11-beta-hydroxysteroid dehydrogenase type 2.

Bioactivity

ChEMBL activities: 22 potent at pChembl ≥ 5 of 27 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
HSD11B1	7.4	IC50	40	nM	CHEMBL_ACT_24777623
HSD11B1	7.21	Ki	62	nM	CHEMBL_ACT_18884249
P51661	7.09	EC50	82	nM	CHEMBL_ACT_10871512
P51661	7.09	IC50	82	nM	CHEMBL_ACT_2720865
HSD11B1	7.08	IC50	83	nM	CHEMBL_ACT_66523
P50172	6.97	IC50	108	nM	CHEMBL_ACT_66521
HSD11B2	6.77	IC50	170	nM	CHEMBL_ACT_18884231
P51661	6.69	IC50	206	nM	CHEMBL_ACT_10914152
P50172	6.61	IC50	243	nM	CHEMBL_ACT_20600852
P50172	6.6	IC50	250	nM	CHEMBL_ACT_5127779
HSD11B1	6.48	IC50	330	nM	CHEMBL_ACT_25044207
HSD11B1	6.48	IC50	330	nM	CHEMBL_ACT_66522
HSD11B1	6.39	IC50	410	nM	CHEMBL_ACT_18884183
HSD11B1	6.3	IC50	500	nM	CHEMBL_ACT_10902254
HSD11B1	6.3	IC50	500	nM	CHEMBL_ACT_3095070
HSD11B1	6.3	IC50	500	nM	CHEMBL_ACT_5127760
HSD11B1	5.79	IC50	1630	nM	CHEMBL_ACT_20600840
HTR1A	5.6	AC50	2500	nM	CHEMBL_ACT_25217531
PTPN1	5.16	Ki	7000	nM	CHEMBL_ACT_29011214
ADRA1A	5.07	AC50	8500	nM	CHEMBL_ACT_25218452
Q9JIP4	5	IC50	10000	nM	CHEMBL_ACT_23255364
CHRM2	5	AC50	9900	nM	CHEMBL_ACT_25215458

Target pathways

Aggregated over 24 target gene(s): GJE1, GJB7, GJB2, GJB6, GJC3, GJB4, GJB3, GJB5, GJD3, GJB1, GJD2, GJA4, GJA5, GJD4, GJA1, GJC1, GJA3, GJC2, GJA8, GJA9, GJA10, PANX1, PANX2, PANX3.

Top Reactome pathways

17 total, by targets touching each:

Pathway	Targets	Genes
Gap junction assembly	19	GJA1, GJA10, GJA3, GJA4, GJA5, GJA8, GJA9, GJB1, GJB2, GJB3, GJB4, GJB5, GJB6, GJB7, GJC1, GJC2, GJD2, GJD3, GJD4
Electric Transmission Across Gap Junctions	5	GJA10, GJC1, GJD2, PANX1, PANX2
Oligomerization of connexins into connexons	3	GJA1, GJB1, GJB2
Transport of connexins along the secretory pathway	3	GJA1, GJB1, GJB2
Mechanical load activates signaling by PIEZO1 and integrins in osteocytes	2	GJA1, PANX1
Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane	1	GJA1
Transport of connexons to the plasma membrane	1	GJB2
Gap junction degradation	1	GJA1
Regulation of gap junction activity	1	GJA1
Formation of annular gap junctions	1	GJA1
The NLRP3 inflammasome	1	PANX1
RHOQ GTPase cycle	1	GJA1
RHOJ GTPase cycle	1	GJA1
EGR2 and SOX10-mediated initiation of Schwann cell myelination	1	GJB1
SARS-CoV-2 targets PDZ proteins in cell-cell junction	1	GJA1
Differentiation of Keratinocytes in Interfollicular Epidermis in Mammalian Skin	1	GJB3
High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells	1	PANX1

Dominant GO biological processes

GO term	Targets
cell-cell signaling	24
transmembrane transport	22
cell communication	21
gap junction assembly	7
monoatomic ion transmembrane transport	6
gap junction-mediated intercellular transport	5
cell communication by electrical coupling	5
sensory perception of sound	3
AV node cell to bundle of His cell communication by electrical coupling	3
visual perception	3
heart development	3
monoatomic cation transport	3
monoatomic ion transport	3
positive regulation of interleukin-1 production	3
lens development in camera-type eye	2

Indications & clinical

Indications

2 indications (2 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
gastroesophageal reflux disease	4	MONDO:0007186	EFO:0003948
peptic ulcer disease	4	MONDO:0004247	HP:0004398

Clinical trials

Total trials: 0.

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.

2 molecules share ≥1 primary target. Top 2 by shared-target count:

Molecule	Source	Status	Shared targets
KANAMYCIN	ChEMBL + PubChem	Phase 4 (approved)	GJA1, GJB2
Probenecid	PubChem	Approved	PANX1