Andrographolide

Identification

Name
Andrographolide
Accession Number
DB05767
Type
Small Molecule
Groups
Investigational
Description

HMPL-004 is a botanical product extracted from a herb that occurs naturally in China. The herb has an extensive history of use in TCM for the treatment of upper respiratory tract infections and other inflammatory and infectious diseases.

Structure
Thumb
Synonyms
Not Available
External IDs
HMPL-004
Categories
UNII
410105JHGR
CAS number
Not Available
Weight
Average: 350.455
Monoisotopic: 350.209324066
Chemical Formula
C20H30O5
InChI Key
BOJKULTULYSRAS-OTESTREVSA-N
InChI
InChI=1S/C20H30O5/c1-12-4-7-16-19(2,9-8-17(23)20(16,3)11-21)14(12)6-5-13-15(22)10-25-18(13)24/h5,14-17,21-23H,1,4,6-11H2,2-3H3/b13-5+/t14-,15-,16+,17-,19+,20+/m1/s1
IUPAC Name
(3E,4S)-3-{2-[(1R,4aS,5R,6R,8aS)-6-hydroxy-5-(hydroxymethyl)-5,8a-dimethyl-2-methylidene-decahydronaphthalen-1-yl]ethylidene}-4-hydroxyoxolan-2-one
SMILES
[H]\C(C[C@]1([H])C(=C)CC[C@]2([H])[C@](C)(CO)[C@]([H])(O)CC[C@@]12C)=C1/C(=O)OC[C@@]1([H])O

Pharmacology

Indication

Investigated for use/treatment in ulcerative colitis.

Pharmacodynamics
Not Available
Mechanism of action

HMPL-004 acts on multiple cellular targets in the inflammatory signal transduction pathways resulting in suppressed inflammation cytokine expression including TNF-α, IL-1β and IL-6. HMPL-004 was demonstrated to inhibit TNF-α and IL-1β production in cell-based assays. HMPL-004 is also able to inhibit NF-kB activation. NF-kB is a family of transcriptional factors that regulate a wide spectrum of genes critically involved in host defence and inflammation. The mechanism of action of HMPL-004 was further supported in laboratory IBD animal models. Treatment of IBD rats with HMPL-004 caused a significant drop in plasma cytokine concentrations, including TNF-α and IL-1β.

TargetActionsOrganism
UTumor necrosis factorNot AvailableHuman
UInterleukin-1 betaNot AvailableHuman
UInterleukin-6Not AvailableHuman
UNuclear factor NF-kappa-B p100 subunitNot AvailableHuman
UNuclear factor NF-kappa-B p105 subunitNot AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of bleeding can be increased when Andrographolide is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of bleeding can be increased when Andrographolide is combined with (S)-Warfarin.
4-hydroxycoumarinThe risk or severity of bleeding can be increased when Andrographolide is combined with 4-hydroxycoumarin.
AbciximabAndrographolide may increase the anticoagulant activities of Abciximab.
AcenocoumarolThe risk or severity of bleeding can be increased when Andrographolide is combined with Acenocoumarol.
Acetylsalicylic acidThe risk or severity of adverse effects can be increased when Andrographolide is combined with Acetylsalicylic acid.
AlaproclateThe risk or severity of hemorrhage can be increased when Alaproclate is combined with Andrographolide.
AldesleukinThe risk or severity of bleeding can be increased when Andrographolide is combined with Aldesleukin.
AlemtuzumabThe risk or severity of bleeding can be increased when Andrographolide is combined with Alemtuzumab.
AloxiprinThe risk or severity of adverse effects can be increased when Andrographolide is combined with Aloxiprin.
Food Interactions
Not Available

References

General References
Not Available
External Links
PubChem Compound
5318517
PubChem Substance
347827741
ChemSpider
4477067
ChEBI
65408
ChEMBL
CHEMBL186141
Wikipedia
Andrographolide

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1, 2CompletedTreatmentRelapsing Remitting Multiple Sclerosis (RRMS)1
1, 2RecruitingTreatmentMultiple Sclerosis, Primary Progressive / Secondary Progressive Multiple Sclerosis (SPMS)1
2CompletedTreatmentUlcerative Colitis (UC)1
3TerminatedTreatmentUlcerative Colitis (UC)2

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.284 mg/mLALOGPS
logP1.57ALOGPS
logP1.66ChemAxon
logS-3.1ALOGPS
pKa (Strongest Acidic)13.48ChemAxon
pKa (Strongest Basic)-2.8ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area86.99 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity94.93 m3·mol-1ChemAxon
Polarizability38.65 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as gamma butyrolactones. These are compounds containing a gamma butyrolactone moiety, which consists of an aliphatic five-member ring with four carbon atoms, one oxygen atom, and bears a ketone group on the carbon adjacent to the oxygen atom.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Lactones
Sub Class
Gamma butyrolactones
Direct Parent
Gamma butyrolactones
Alternative Parents
Tetrahydrofurans / Enoate esters / Secondary alcohols / Cyclic alcohols and derivatives / Oxacyclic compounds / Monocarboxylic acids and derivatives / Primary alcohols / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
Gamma butyrolactone / Cyclic alcohol / Tetrahydrofuran / Enoate ester / Alpha,beta-unsaturated carboxylic ester / Carboxylic acid ester / Secondary alcohol / Monocarboxylic acid or derivatives / Carboxylic acid derivative / Oxacycle
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
secondary alcohol, primary alcohol, gamma-lactone, carbobicyclic compound, labdane diterpenoid (CHEBI:65408)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Tumor necrosis factor receptor binding
Specific Function
Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct ac...
Gene Name
TNF
Uniprot ID
P01375
Uniprot Name
Tumor necrosis factor
Molecular Weight
25644.15 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Protein domain specific binding
Specific Function
Potent proinflammatory cytokine. Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil influx and activation, T-cell activation and cytokine production, ...
Gene Name
IL1B
Uniprot ID
P01584
Uniprot Name
Interleukin-1 beta
Molecular Weight
30747.7 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Interleukin-6 receptor binding
Specific Function
Cytokine with a wide variety of biological functions. It is a potent inducer of the acute phase response. Plays an essential role in the final differentiation of B-cells into Ig-secreting cells Inv...
Gene Name
IL6
Uniprot ID
P05231
Uniprot Name
Interleukin-6
Molecular Weight
23717.965 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Transcriptional activator activity, rna polymerase ii core promoter proximal region sequence-specific binding
Specific Function
NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related...
Gene Name
NFKB2
Uniprot ID
Q00653
Uniprot Name
Nuclear factor NF-kappa-B p100 subunit
Molecular Weight
96748.355 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Transcriptional repressor activity, rna polymerase ii transcription regulatory region sequence-specific binding
Specific Function
NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related...
Gene Name
NFKB1
Uniprot ID
P19838
Uniprot Name
Nuclear factor NF-kappa-B p105 subunit
Molecular Weight
105355.175 Da

Drug created on November 18, 2007 11:27 / Updated on November 02, 2018 06:12