Natural Product: NPC49529

Natural Product IDNPC49529
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 VPCHZECKYCDVSA-WEVVVXLNSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 45783180
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002650] Diarylheptanoids
        • [CHEMONTID:0002651] Linear diarylheptanoids

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 VPCHZECKYCDVSA-WEVVVXLNSA-N
Standard InCHI InChI=1S/C19H20O2/c20-18(13-10-16-6-2-1-3-7-16)9-5-4-8-17-11-14-19(21)15-12-17/h1-3,5-7,9,11-12,14-15,21H,4,8,10,13H2/b9-5+
SMILES c1ccc(cc1)CCC(=O)/C=C/CCc1ccc(cc1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   280.15 Volume:   316.556
?
Van der Waals volume.
Dense:   0.885 LogP:   3.521
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.34
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.694
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   14.0
TPSA:   37.3
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.776 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.016 Fsp3:   0.211
MCE-18:   10.0
?
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:   0.862 Fluc inhibitor:   0.51
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.019
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.612
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.97 Promiscuous compounds:   0.094

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.762 MDCK Permeability:   -4.738
Pgp-inhibitor:   0.999 Pgp-substrate:   0.026
PAMPA:   0.033
?
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):   0.0
20% Bioavailability (F20%):   0.051 30% Bioavailability (F30%):   0.878
50% Bioavailability (F50%):   0.994

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.002
Plasma Protein Binding (PPB):   97.949% Volume Distribution (VD):   -0.452
Fu: 1.111%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.918
OATP1B3 inhibitor:   0.744 BCRP inhibitor:   0.059
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.035 CYP1A2-substrate:   0.858
CYP2C19-inhibitor:   0.677 CYP2C19-substrate:   0.957
CYP2C9-inhibitor:   0.421 CYP2C9-substrate:   0.231
CYP2D6-inhibitor:   0.792 CYP2D6-substrate:   0.908
CYP3A4-inhibitor:   0.006 CYP3A4-substrate:   0.039
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.999
HLM stability:   0.953
?
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):  9.582 Half-life (T1/2):  0.474

ADMET: Toxicity

hERG Blockers:  0.756 hERG Blockers (10um):  0.893
Human Hepatotoxicity (H-HT):  0.829 Drug-induced Liver Injury (DILI):  0.048
AMES Toxicity:  0.458 Rat Oral Acute Toxicity:  0.068
Maximum Recommended Daily Dose:  0.584 Skin Sensitization:  0.996
Carcinogencity:  0.146 Eye Corrosion:  0.022
Eye Irritation:  0.869 Respiratory Toxicity:  0.55
Drug-induced Neurotoxicity:  0.415 Ototoxicity:  0.394
Hematotoxicity:  0.134 Drug-induced Nephrotoxicity:  0.37
Genotoxicity:  0.238 RPMI-8226 Immunitoxicity:  0.036
A549 Cytotoxicity:  0.329 Hek293 Cytotoxicity:  0.723
BCF:   1.568
?
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:   4.66
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.521
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.295
?
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
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. root n.a. PMID[18484537]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. rhizome n.a. PMID[18484537]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota rhizomes n.a. n.a. PMID[19615910]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[29323912]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. rhizome n.a. PMID[731398]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. root n.a. PMID[731398]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO23911 Alpinia officinarum Species Zingiberaceae 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

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT113 Cell line RAW264.7 Mus musculus Inhibition = 69.0 % PMID[33422907]
NPT113 Cell line RAW264.7 Mus musculus IC50 = 5.0 ug.mL-1 PMID[33422907]
NPT113 Cell line RAW264.7 Mus musculus Inhibition = 70.0 % PMID[33422907]
NPT113 Cell line RAW264.7 Mus musculus Inhibition = 71.0 % PMID[33422907]
NPT113 Cell line RAW264.7 Mus musculus Inhibition = 50.0 % PMID[33422907]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT32 Organism Mus musculus Mus musculus ID50 = 0.8 umol PMID[33422907]





 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 NPC49529 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
0.8919 High Similarity NPC29989
0.7838 Intermediate Similarity NPC151405
0.7083 Intermediate Similarity NPC179777
0.6905 Remote Similarity NPC61062
0.6875 Remote Similarity NPC123228
0.6875 Remote Similarity NPC123722
0.6444 Remote Similarity NPC602856
0.625 Remote Similarity NPC95178
0.6154 Remote Similarity NPC260000
0.6042 Remote Similarity NPC5018
0.5625 Remote Similarity NPC69332
0.551 Remote Similarity NPC321252
0.551 Remote Similarity NPC252544
0.5476 Remote Similarity NPC188677
0.5227 Remote Similarity NPC113460
0.5192 Remote Similarity NPC8931
0.5192 Remote Similarity NPC277394
0.5128 Remote Similarity NPC74458
0.5106 Remote Similarity NPC289201

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC49529 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
NPD

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