Andrographolide

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Identification

Generic Name

Andrographolide

DrugBank Accession Number

DB05767

Background

Andrographolide (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.

Type

Small Molecule

Groups

Investigational

Structure

Similar Structures

Weight: Average: 350.455
Monoisotopic: 350.209324066
Chemical Formula: C₂₀H₃₀O₅

Synonyms

3α,14,15,18-tetrahydroxy-5b,9bH,10a-labda-8(20),12-dien-16-oic acid γ-Lactone

External IDs

HMPL-004
HMPL004

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Pharmacology

Indication

Investigated for use/treatment in ulcerative colitis.

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Contraindications & Blackbox Warnings

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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.

Target	Actions	Organism
UTumor necrosis factor	Not Available	Humans
UInterleukin-1 beta	Not Available	Humans
UInterleukin-6	Not Available	Humans
UNuclear factor NF-kappa-B p100 subunit	Not Available	Humans
UNuclear factor NF-kappa-B p105 subunit	Not Available	Humans

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

Adverse Effects

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Toxicity

Not Available

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

Drug	Interaction
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Abciximab	The risk or severity of bleeding can be increased when Andrographolide is combined with Abciximab.
Abrocitinib	The risk or severity of bleeding and thrombocytopenia can be increased when Andrographolide is combined with Abrocitinib.
Aceclofenac	The risk or severity of bleeding can be increased when Aceclofenac is combined with Andrographolide.
Acemetacin	The risk or severity of bleeding can be increased when Acemetacin is combined with Andrographolide.
Acenocoumarol	The risk or severity of bleeding can be increased when Andrographolide is combined with Acenocoumarol.

Food Interactions

Not Available

Chemical Identifiers

UNII: 410105JHGR
CAS number: 5508-58-7
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@]12CCC(=C)[C@@H](C\C=C3/[C@H](O)COC3=O)[C@]1(C)CC[C@@H](O)[C@@]2(C)CO

References

General References

Not Available

External Links

PubChem Compound: 5318517
PubChem Substance: 347827741
ChemSpider: 4477067
BindingDB: 50084419
ChEBI: 65408
ChEMBL: CHEMBL186141
ZINC: ZINC000003881797
Wikipedia: Andrographolide

Clinical Trials

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Phase	Status	Purpose	Conditions	Count	Start Date	Why Stopped	100+ additional columns
Unlock 175K+ rows when you subscribe.View sample data
4	Unknown Status	Treatment	Acute Exacerbation of Chronic Bronchitis (AECB)	1	somestatus	stop reason	just information to hide
4	Unknown Status	Treatment	Acute Tonsillitis	1	somestatus	stop reason	just information to hide
4	Unknown Status	Treatment	Acute Tracheobronchitis	1	somestatus	stop reason	just information to hide
3	Terminated	Treatment	Ulcerative Colitis	2	somestatus	stop reason	just information to hide
2	Completed	Treatment	Crohn's Disease (CD)	1	somestatus	stop reason	just information to hide

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

Property	Value	Source
Water Solubility	0.284 mg/mL	ALOGPS
logP	1.57	ALOGPS
logP	1.66	Chemaxon
logS	-3.1	ALOGPS
pKa (Strongest Acidic)	13.48	Chemaxon
pKa (Strongest Basic)	-2.8	Chemaxon
Physiological Charge	0	Chemaxon
Hydrogen Acceptor Count	4	Chemaxon
Hydrogen Donor Count	3	Chemaxon
Polar Surface Area	86.99 Å²	Chemaxon
Rotatable Bond Count	3	Chemaxon
Refractivity	94.93 m³·mol^-1	Chemaxon
Polarizability	38.27 Å³	Chemaxon
Number of Rings	3	Chemaxon
Bioavailability	1	Chemaxon
Rule of Five	Yes	Chemaxon
Ghose Filter	Yes	Chemaxon
Veber's Rule	No	Chemaxon
MDDR-like Rule	No	Chemaxon

Predicted ADMET Features

Not Available

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	splash10-0159-0029000000-ba800d55dfc663f742a2
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	splash10-0a4j-0019000000-25a210618c0718588eac
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	splash10-0pbm-0049000000-8434c56f20900b80f9a6
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	splash10-001i-1394000000-f69c00e86ac49f699d0f
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	splash10-003v-2098000000-652cb509a614bd920e29
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	splash10-0002-9681000000-6f3aaf6c20f2eb37f3af
Predicted 1H NMR Spectrum	1D NMR	Not Applicable
Predicted 13C NMR Spectrum	1D NMR	Not Applicable

Chromatographic Properties

Collision Cross Sections (CCS)

Adduct	CCS Value (Å²)	Source type	Source
[M-H]-	195.6312579	predicted	DarkChem Lite v0.1.0
[M-H]-	190.2163579	predicted	DarkChem Lite v0.1.0
[M-H]-	181.89417	predicted	DeepCCS 1.0 (2019)
[M+H]+	195.7212579	predicted	DarkChem Lite v0.1.0
[M+H]+	190.0616579	predicted	DarkChem Lite v0.1.0
[M+H]+	183.79454	predicted	DeepCCS 1.0 (2019)
[M+Na]+	193.8002579	predicted	DarkChem Lite v0.1.0
[M+Na]+	189.6206579	predicted	DarkChem Lite v0.1.0
[M+Na]+	189.70705	predicted	DeepCCS 1.0 (2019)

Targets

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Details1. Tumor necrosis factor

Kind: Protein
Organism: Humans
Pharmacological action: Unknown

General 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 action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation. Impairs regulatory T-cells (Treg) function in individuals with rheumatoid arthritis via FOXP3 dephosphorylation. Up-regulates the expression of protein phosphatase 1 (PP1), which dephosphorylates the key 'Ser-418' residue of FOXP3, thereby inactivating FOXP3 and rendering Treg cells functionally defective (PubMed:23396208). Key mediator of cell death in the anticancer action of BCG-stimulated neutrophils in combination with DIABLO/SMAC mimetic in the RT4v6 bladder cancer cell line (PubMed:16829952, PubMed:22517918, PubMed:23396208). Induces insulin resistance in adipocytes via inhibition of insulin-induced IRS1 tyrosine phosphorylation and insulin-induced glucose uptake. Induces GKAP42 protein degradation in adipocytes which is partially responsible for TNF-induced insulin resistance (By similarity). Plays a role in angiogenesis by inducing VEGF production synergistically with IL1B and IL6 (PubMed:12794819). Promotes osteoclastogenesis and therefore mediates bone resorption (By similarity)
Specific Function: cytokine activity
Gene Name: TNF
Uniprot ID: P01375
Uniprot Name: Tumor necrosis factor
Molecular Weight: 25644.15 Da

Details2. Interleukin-1 beta

Kind: Protein
Organism: Humans
Pharmacological action: Unknown

General Function: Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil influx and activation, T-cell activation and cytokine production, B-cell activation and antibody production, and fibroblast proliferation and collagen production (PubMed:3920526). Promotes Th17 differentiation of T-cells. Synergizes with IL12/interleukin-12 to induce IFNG synthesis from T-helper 1 (Th1) cells (PubMed:10653850). Plays a role in angiogenesis by inducing VEGF production synergistically with TNF and IL6 (PubMed:12794819). Involved in transduction of inflammation downstream of pyroptosis: its mature form is specifically released in the extracellular milieu by passing through the gasdermin-D (GSDMD) pore (PubMed:33377178, PubMed:33883744). Acts as a sensor of S.pyogenes infection in skin: cleaved and activated by pyogenes SpeB protease, leading to an inflammatory response that prevents bacterial growth during invasive skin infection (PubMed:28331908)
Specific Function: cytokine activity
Gene Name: IL1B
Uniprot ID: P01584
Uniprot Name: Interleukin-1 beta
Molecular Weight: 30747.7 Da

Details3. Interleukin-6

Kind: Protein
Organism: Humans
Pharmacological action: Unknown

General Function: Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the intracellular IL6-signaling pathway (Probable). The interaction with the membrane-bound IL6R and IL6ST stimulates 'classic signaling', whereas the binding of IL6 and soluble IL6R to IL6ST stimulates 'trans-signaling'. Alternatively, 'cluster signaling' occurs when membrane-bound IL6:IL6R complexes on transmitter cells activate IL6ST receptors on neighboring receiver cells (Probable)
Specific Function: cytokine activity
Gene Name: IL6
Uniprot ID: P05231
Uniprot Name: Interleukin-6
Molecular Weight: 23717.965 Da

Details4. Nuclear factor NF-kappa-B p100 subunit

Kind: Protein
Organism: Humans
Pharmacological action: Unknown

General 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 to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. In a non-canonical activation pathway, the MAP3K14-activated CHUK/IKKA homodimer phosphorylates NFKB2/p100 associated with RelB, inducing its proteolytic processing to NFKB2/p52 and the formation of NF-kappa-B RelB-p52 complexes. The NF-kappa-B heterodimeric RelB-p52 complex is a transcriptional activator. The NF-kappa-B p52-p52 homodimer is a transcriptional repressor. NFKB2 appears to have dual functions such as cytoplasmic retention of attached NF-kappa-B proteins by p100 and generation of p52 by a cotranslational processing. The proteasome-mediated process ensures the production of both p52 and p100 and preserves their independent function. p52 binds to the kappa-B consensus sequence 5'-GGRNNYYCC-3', located in the enhancer region of genes involved in immune response and acute phase reactions. p52 and p100 are respectively the minor and major form; the processing of p100 being relatively poor. Isoform p49 is a subunit of the NF-kappa-B protein complex, which stimulates the HIV enhancer in synergy with p65. In concert with RELB, regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-BMAL1 heterodimer
Specific Function: DNA-binding transcription activator activity, RNA polymerase II-specific
Gene Name: NFKB2
Uniprot ID: Q00653
Uniprot Name: Nuclear factor NF-kappa-B p100 subunit
Molecular Weight: 96748.355 Da

Details5. Nuclear factor NF-kappa-B p105 subunit

Kind: Protein
Organism: Humans
Pharmacological action: Unknown

General 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 to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52 and the heterodimeric p65-p50 complex appears to be most abundant one. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. NF-kappa-B heterodimeric p65-p50 and RelB-p50 complexes are transcriptional activators. The NF-kappa-B p50-p50 homodimer is a transcriptional repressor, but can act as a transcriptional activator when associated with BCL3. NFKB1 appears to have dual functions such as cytoplasmic retention of attached NF-kappa-B proteins by p105 and generation of p50 by a cotranslational processing. The proteasome-mediated process ensures the production of both p50 and p105 and preserves their independent function, although processing of NFKB1/p105 also appears to occur post-translationally. p50 binds to the kappa-B consensus sequence 5'-GGRNNYYCC-3', located in the enhancer region of genes involved in immune response and acute phase reactions. In a complex with MAP3K8, NFKB1/p105 represses MAP3K8-induced MAPK signaling; active MAP3K8 is released by proteasome-dependent degradation of NFKB1/p105
Specific Function: actinin binding
Gene Name: NFKB1
Uniprot ID: P19838
Uniprot Name: Nuclear factor NF-kappa-B p105 subunit
Molecular Weight: 105355.175 Da

Drug created at November 18, 2007 18:27 / Updated at June 12, 2020 16:52

Andrographolide

Identification

Structure for Andrographolide (DB05767)

Pharmacology

Interactions

Categories

Chemical Identifiers

References

Clinical Trials

Clinical Trial & Rare Diseases Add-on Data Package

Pharmacoeconomics

Properties

Spectra

Collision Cross Sections (CCS)

Targets