Natural Product: NPC16967

Natural Product IDNPC16967
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 14-Deoxy-11,12-Didehydro-15-Isopropylideneandrographolide
IUPAC Name 3-[(E)-2-[(1R,4aS,5R,6R,8aR)-6-hydroxy-5-(hydroxymethyl)-5,8a-dimethyl-2-methylidene-3,4,4a,6,7,8-hexahydro-1H-naphthalen-1-yl]ethenyl]-5-propan-2-ylidenefuran-2-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL205812
PubChem CID 637300
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001283] Terpene lactones
          • [CHEMONTID:0001538] Diterpene lactones

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

  Chemical Representations

Standard InCHIKey NOBUCQWGEOIPGK-ZCDHJCLFSA-N
Standard InCHI InChI=1S/C23H32O4/c1-14(2)18-12-16(21(26)27-18)7-8-17-15(3)6-9-19-22(17,4)11-10-20(25)23(19,5)13-24/h7-8,12,17,19-20,24-25H,3,6,9-11,13H2,1-2,4-5H3/b8-7+/t17-,19+,20-,22+,23+/m1/s1
SMILES OC[C@]1(C)[C@H](O)CC[C@@]2([C@@H]1CCC(=C)[C@H]2/C=C/C1=CC(=C(C)C)OC1=O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   372.23 Volume:   402.673
?
Van der Waals volume.
Dense:   0.924 LogP:   3.05
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.043
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.488
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The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   20.0
TPSA:   66.76
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.579 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.822 Fsp3:   0.609
MCE-18:   57.189
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.62 Fluc inhibitor:   0.748
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.148
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.012
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.495 Promiscuous compounds:   0.324

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.227 MDCK Permeability:   -4.929
Pgp-inhibitor:   0.075 Pgp-substrate:   0.014
PAMPA:   0.685
?
The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).
 Human Intestinal Absorption (HIA):   0.032
20% Bioavailability (F20%):   0.806 30% Bioavailability (F30%):   0.697
50% Bioavailability (F50%):   0.993

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.572 MRP1:   0.875
Plasma Protein Binding (PPB):   96.111% Volume Distribution (VD):   -0.185
Fu: 3.054%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.922
OATP1B3 inhibitor:   0.959 BCRP inhibitor:   0.131
BSEP inhibitor:   0.908

ADMET: Metabolism

CYP1A2-inhibitor:   0.66 CYP1A2-substrate:   0.587
CYP2C19-inhibitor:   0.881 CYP2C19-substrate:   0.491
CYP2C9-inhibitor:   0.262 CYP2C9-substrate:   0.011
CYP2D6-inhibitor:   0.6 CYP2D6-substrate:   0.01
CYP3A4-inhibitor:   0.009 CYP3A4-substrate:   0.868
CYP2B6-substrate:   0.005 CYP2C8-inhibitor:   0.999
HLM stability:   0.391
?
Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):  6.405 Half-life (T1/2):  1.247

ADMET: Toxicity

hERG Blockers:  0.03 hERG Blockers (10um):  0.187
Human Hepatotoxicity (H-HT):  0.781 Drug-induced Liver Injury (DILI):  0.765
AMES Toxicity:  0.616 Rat Oral Acute Toxicity:  0.556
Maximum Recommended Daily Dose:  0.638 Skin Sensitization:  0.999
Carcinogencity:  0.943 Eye Corrosion:  0.027
Eye Irritation:  0.948 Respiratory Toxicity:  0.562
Drug-induced Neurotoxicity:  0.386 Ototoxicity:  0.534
Hematotoxicity:  0.706 Drug-induced Nephrotoxicity:  0.96
Genotoxicity:  0.846 RPMI-8226 Immunitoxicity:  0.088
A549 Cytotoxicity:  0.423 Hek293 Cytotoxicity:  0.299
BCF:   1.128
?
Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].
 IGC50:   3.811
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.37
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.803
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96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

  Species Source

Organism ID Organism Name Taxonomy Level Family SuperKingdom Isolation Part Collection Location Collection Time Reference
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. n.a. n.a. DOI[10.1111/ppl.12252]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. leaf n.a. PMID[15894448]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. root n.a. PMID[15894448]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota aerial parts purchased in Juhuacun herbal market, Kunming, Yunnan Province, China 2002-Oct PMID[16562826]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. n.a. n.a. PMID[18357994]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. leaf n.a. PMID[21598983]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. leaf n.a. PMID[22026410]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. n.a. n.a. PMID[8377022]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[UNPD]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].



  NP Quantity Composition/Concentration

Organism ID Organism Name Organism Material Preparation Organism Part NP Quantity (Standard) NP Quantity (Minimum) NP Quantity (Maximum) Quantity Unit Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].



 Biological Activity

Molecular-level activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT497 Individual protein Maltase-glucoamylase Homo sapiens Inhibition = 17.1 % PMID[17428667]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference





 Experimental ADME

Experiment Model Experiment Tissue ADME Type ADME Relation ADME Value ADME Unit Reference





 Experimental Toxicity

Quantitative toxicity

Experiment Model Experiment Organism Toxicity Type Toxicity Relation Toxicity Value Toxicity Unit Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption
Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]


  Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

●  The left chart: Distribution of similarity level between NPC16967 and all remaining natural products in the NPASS database.
●  The right table: Most similar natural products (Tc>=0.5 or Top200).

Similarity Score Similarity Level Natural Product ID
0.7193 Intermediate Similarity NPC152778
0.7193 Intermediate Similarity NPC205034
0.7069 Intermediate Similarity NPC474440
0.6 Remote Similarity NPC476602
0.5833 Remote Similarity NPC310479
0.5469 Remote Similarity NPC162615
0.5397 Remote Similarity NPC139692
0.5385 Remote Similarity NPC191521
0.5231 Remote Similarity NPC159763
0.5231 Remote Similarity NPC278386
0.5231 Remote Similarity NPC124512
0.5161 Remote Similarity NPC79945
0.5156 Remote Similarity NPC131813
0.5152 Remote Similarity NPC72845
0.5152 Remote Similarity NPC242848
0.5082 Remote Similarity NPC476949

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

●  The left chart: Distribution of similarity level between NPC16967 and all drugs/candidates.
●  The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

Similarity Score Similarity Level Drug ID Developmental Stage
0.5231 Remote Similarity NPD4225 Phase 3

Bioactivity similarity

  Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity
B: biological targets similarity
C: networks similarity
D: cell-based bioactivity similarity
E: similarity based on clinical data