Natural Product: NPC254761

Natural Product IDNPC254761
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 GCCMDTDROAUVAS-FNORWQNLSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 5318568
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 GCCMDTDROAUVAS-FNORWQNLSA-N
Standard InCHI InChI=1S/C22H26O6/c1-26-19-12-15(9-11-18(19)24)6-4-5-7-17(23)10-8-16-13-20(27-2)22(25)21(14-16)28-3/h5,7,9,11-14,24-25H,4,6,8,10H2,1-3H3/b7-5+
SMILES COc1cc(CC/C=C/C(=O)CCc2cc(c(c(c2)OC)O)OC)ccc1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   386.17 Volume:   403.605
?
Van der Waals volume.
Dense:   0.957 LogP:   2.559
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.638
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.065
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   10.0 Rigid Bonds:   14.0
TPSA:   85.22
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.604 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.436 Fsp3:   0.318
MCE-18:   14.0
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.376 Fluc inhibitor:   0.075
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.023
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.549
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.635 Promiscuous compounds:   0.15

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.187 MDCK Permeability:   -4.79
Pgp-inhibitor:   0.998 Pgp-substrate:   0.081
PAMPA:   0.0
?
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):   0.004
20% Bioavailability (F20%):   0.057 30% Bioavailability (F30%):   0.254
50% Bioavailability (F50%):   0.977

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.064
Plasma Protein Binding (PPB):   97.902% Volume Distribution (VD):   -0.541
Fu: 1.572%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.987 BCRP inhibitor:   0.214
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.995 CYP1A2-substrate:   0.991
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.989
CYP2C9-inhibitor:   0.999 CYP2C9-substrate:   0.073
CYP2D6-inhibitor:   0.618 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   0.428 CYP3A4-substrate:   0.871
CYP2B6-substrate:   0.001 CYP2C8-inhibitor:   1.0
HLM stability:   0.931
?
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):  7.404 Half-life (T1/2):  1.169

ADMET: Toxicity

hERG Blockers:  0.529 hERG Blockers (10um):  0.793
Human Hepatotoxicity (H-HT):  0.738 Drug-induced Liver Injury (DILI):  0.168
AMES Toxicity:  0.435 Rat Oral Acute Toxicity:  0.119
Maximum Recommended Daily Dose:  0.629 Skin Sensitization:  0.975
Carcinogencity:  0.188 Eye Corrosion:  0.002
Eye Irritation:  0.656 Respiratory Toxicity:  0.836
Drug-induced Neurotoxicity:  0.313 Ototoxicity:  0.478
Hematotoxicity:  0.259 Drug-induced Nephrotoxicity:  0.455
Genotoxicity:  0.174 RPMI-8226 Immunitoxicity:  0.15
A549 Cytotoxicity:  0.417 Hek293 Cytotoxicity:  0.66
BCF:   1.47
?
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:   4.321
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.32
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.915
?
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
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/j.jarmap.2018.11.004]
NPO403 Gentiana lutea Species Gentianaceae Eukaryota n.a. n.a. n.a. PMID[10705751]
NPO403 Gentiana lutea Species Gentianaceae Eukaryota n.a. seed n.a. PMID[12822897]
NPO403 Gentiana lutea Species Gentianaceae Eukaryota n.a. root n.a. PMID[18064621]
NPO403 Gentiana lutea Species Gentianaceae Eukaryota n.a. n.a. n.a. PMID[18064621]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota rhizomes n.a. n.a. PMID[18177011]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[19271742]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[20590154]
NPO403 Gentiana lutea Species Gentianaceae Eukaryota n.a. root n.a. PMID[24257774]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[32872604]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[36352904]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[39679248]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[39680258]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. rhizome n.a. PMID[8064299]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[8064299]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO403 Gentiana lutea Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26632 Swertia chirayita Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. Database[FooDB]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota Plant n.a. n.a. Database[FooDB]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota Resin, Exudate, Sap n.a. n.a. Database[FooDB]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota Rhizome n.a. n.a. Database[FooDB]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota Root n.a. n.a. Database[FooDB]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. Database[FooDB]
NPO403 Gentiana lutea Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. Database[Phenol-Explorer]
NPO403 Gentiana lutea Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO26632 Swertia chirayita Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO403 Gentiana lutea Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO403 Gentiana lutea Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO26632 Swertia chirayita Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO403 Gentiana lutea Species Gentianaceae 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
NPO20553 Zingiber officinale Raw Rhizome 0.47 0.47 0.47 mg/100g Database [DUKE]

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

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 NPC254761 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
0.9091 High Similarity NPC5018
0.8333 Intermediate Similarity NPC123228
0.8333 Intermediate Similarity NPC123722
0.8163 Intermediate Similarity NPC179777
0.7347 Intermediate Similarity NPC114298
0.72 Intermediate Similarity NPC4181
0.6957 Remote Similarity NPC299406
0.6923 Remote Similarity NPC164778
0.6792 Remote Similarity NPC257976
0.6792 Remote Similarity NPC273686
0.6792 Remote Similarity NPC242372
0.6792 Remote Similarity NPC312404
0.6667 Remote Similarity NPC231572
0.6596 Remote Similarity NPC17943
0.6327 Remote Similarity NPC127937
0.6071 Remote Similarity NPC276466
0.6042 Remote Similarity NPC29989
0.5926 Remote Similarity NPC303680
0.5918 Remote Similarity NPC61062
0.5849 Remote Similarity NPC98631
0.5849 Remote Similarity NPC206615
0.5849 Remote Similarity NPC481914
0.5745 Remote Similarity NPC8547
0.5741 Remote Similarity NPC53305
0.5636 Remote Similarity NPC201777
0.5636 Remote Similarity NPC604524
0.5625 Remote Similarity NPC193544
0.5577 Remote Similarity NPC49529
0.5577 Remote Similarity NPC602856
0.5536 Remote Similarity NPC137427
0.5439 Remote Similarity NPC481913
0.5439 Remote Similarity NPC163083
0.5435 Remote Similarity NPC156840
0.5424 Remote Similarity NPC304622
0.5385 Remote Similarity NPC177291
0.5345 Remote Similarity NPC257589
0.5333 Remote Similarity NPC84076
0.5333 Remote Similarity NPC151167
0.5254 Remote Similarity NPC229497
0.5254 Remote Similarity NPC485985
0.5246 Remote Similarity NPC65935
0.5246 Remote Similarity NPC319282
0.5208 Remote Similarity NPC257124
0.5179 Remote Similarity NPC159968
0.5167 Remote Similarity NPC20287
0.5167 Remote Similarity NPC215941
0.5167 Remote Similarity NPC123196
0.5167 Remote Similarity NPC20404
0.5167 Remote Similarity NPC311419
0.5161 Remote Similarity NPC90128
0.5094 Remote Similarity NPC312675
0.5094 Remote Similarity NPC262156
0.5094 Remote Similarity NPC184651
0.5094 Remote Similarity NPC113865
0.5082 Remote Similarity NPC12022
0.5082 Remote Similarity NPC275724
0.5082 Remote Similarity NPC244246
0.5082 Remote Similarity NPC278308
0.5082 Remote Similarity NPC611247

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC254761 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
0.5208 Remote Similarity NPD228 Phase 0

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