Andrographolide

Summary

Andrographolide (CHEMBL186141) is a phase-3 clinical-stage small-molecule anti-inflammatory drug targeting TAS2R8, TAS2R50, and TAS2R46; indicated across 4 conditions including ulcerative colitis and crohn disease.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 3 (TAS2R8, TAS2R50, TAS2R46)
• Indications: 4 conditions
• Clinical trials: 6
• Chemistry: 350.4 Da · C20H30O5

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL186141
Name	Andrographolide
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	5318517
ChEBI	CHEBI:65408
Molecular formula	C20H30O5
Molecular weight	350.4
InChIKey	BOJKULTULYSRAS-OTESTREVSA-N

SMILES: C[C@@]12CC[C@H]([C@@]([C@H]1CCC(=C)[C@H]2C/C=C/3\[C@@H](COC3=O)O)(C)CO)O

IUPAC name: (3E,4S)-3-[2-[(1R,4aS,5R,6R,8aS)-6-hydroxy-5-(hydroxymethyl)-5,8a-dimethyl-2-methylidene-3,4,4a,6,7,8-hexahydro-1H-naphthalen-1-yl]ethylidene]-4-hydroxyoxolan-2-one

ChEBI definition: A labdane diterpenoid isolated from the leaves and roots of Andrographis paniculata that exhibits anti-HIV, anti-inflammatory and antineoplastic properties.

Pharmacological roles (ChEBI): anti-inflammatory drug, anti-HIV agent, antineoplastic agent.

Other ChEBI roles (chemical / environmental): metabolite.

Also known as: Andrographolide, HMPL-004, HMPL004, NSC-383468, andrographolide, SID93576922, SID144205061, ANDROGRAPHOLIDE, SID50109887

Patent coverage: 164 distinct patent families (404 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
TAS2R8	TAS2R8	Agonist	3.96	0%	Q9NYW2
TAS2R50	TAS2R50	Agonist	4.64	0.1%	P59544
TAS2R46	TAS2R46	Agonist	4.89	2.2%	P59540

Broader ChEMBL bioactivity targets: 4 (assay-derived). Sample: Bile acid receptor, Fatty acid-binding protein, adipocyte, Nuclear factor NF-kappa-B p105 subunit, Replicase polyprotein 1ab.

Bioactivity

ChEMBL activities: 3 potent at pChembl ≥ 5 of 5 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
FABP4	6.05	IC50	900	nM	CHEMBL_ACT_25901555
NR1H4	5.01	IC50	9700	nM	CHEMBL_ACT_19045228
NR1H4	5.01	IC50	9700	nM	CHEMBL_ACT_19045229

Target pathways

Aggregated over 3 target gene(s): TAS2R8, TAS2R50, TAS2R46.

Top Reactome pathways

9 total, by targets touching each:

Pathway	Targets	Genes
Signal Transduction	3	TAS2R46, TAS2R50, TAS2R8
Signaling by GPCR	3	TAS2R46, TAS2R50, TAS2R8
GPCR downstream signalling	3	TAS2R46, TAS2R50, TAS2R8
G alpha (i) signalling events	3	TAS2R46, TAS2R50, TAS2R8
Class C/3 (Metabotropic glutamate/pheromone receptors)	3	TAS2R46, TAS2R50, TAS2R8
GPCR ligand binding	3	TAS2R46, TAS2R50, TAS2R8
Sensory Perception	3	TAS2R46, TAS2R50, TAS2R8
Sensory perception of taste	3	TAS2R46, TAS2R50, TAS2R8
Sensory perception of sweet, bitter, and umami (glutamate) taste	3	TAS2R46, TAS2R50, TAS2R8

Dominant GO biological processes

GO term	Targets
detection of chemical stimulus involved in sensory perception of bitter taste	3
signal transduction	3
G protein-coupled receptor signaling pathway	3
sensory perception of taste	3

Indications & clinical

Indications

4 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
ulcerative colitis	3	MONDO:0005101	EFO:0000729
Crohn disease	2	MONDO:0005011	EFO:0000384
colorectal neoplasm	2	MONDO:0005335	EFO:0004142
primary progressive multiple sclerosis	1	MONDO:0000451	EFO:0008520

Clinical trials

Total trials: 6.

Phase distribution

Phase	Trials
PHASE4	3
PHASE3	2
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03132610	PHASE4	UNKNOWN	A Study of Andrographolide Sulfonate in Patients With Acute Exacerbation of Chronic Bronchitis
NCT03132623	PHASE4	UNKNOWN	Evaluate the Efficacy and Safety of Andrographolide Sulfonate in Patients With Acute Bronchitis
NCT03134443	PHASE4	UNKNOWN	Evaluate the Efficacy and Safety of Andrographolide Sulfonate in Patients With Acute Tonsillitis
NCT01805791	PHASE3	TERMINATED	A Phase III Trial of HMPL-004 in Patients With Mild to Moderate Active Ulcerative Colitis
NCT01882764	PHASE3	TERMINATED	HMPL-004 Maintenance Treatment in Subjects With Mild to Moderate Ulcerative Colitis
NCT00655733	PHASE2	COMPLETED	Phase II Study of HMPL-004 in Subjects With Crohn’s Disease

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
ISOPROTERENOL	ChEMBL	Phase 4 (approved)	TAS2R46, TAS2R50, TAS2R8
DEXTROMETHORPHAN	ChEMBL	Phase 4 (approved)	TAS2R46