Natural Product: NPC472438

Natural Product IDNPC472438
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 GGNGEESEARSAMF-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3407503
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0002585] O-methylated flavonoids
          • [CHEMONTID:0002591] 6-O-methylated flavonoids

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 GGNGEESEARSAMF-UHFFFAOYSA-N
Standard InCHI InChI=1S/C20H20O9/c1-24-12-6-9(7-13(25-2)19(12)27-4)17-20(28-5)16(23)14-11(29-17)8-10(21)18(26-3)15(14)22/h6-8,21-22H,1-5H3
SMILES COc1c(OC)cc(cc1OC)c1oc2cc(O)c(c(c2c(=O)c1OC)O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   404.11 Volume:   386.827
?
Van der Waals volume.
Dense:   1.045 LogP:   1.995
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.205
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.076
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   18.0
TPSA:   116.82
?
Topological Polar Surface Area.
 H-Bond Acceptor:   9.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   9.0

MedChem Properties

QED Drug-Likeness Score:   0.639 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.57 Fsp3:   0.25
MCE-18:   21.0
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.196 Fluc inhibitor:   0.305
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.835
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.705
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.364 Promiscuous compounds:   0.567

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.226 MDCK Permeability:   -4.756
Pgp-inhibitor:   0.971 Pgp-substrate:   0.238
PAMPA:   0.031
?
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):   0.018
20% Bioavailability (F20%):   0.016 30% Bioavailability (F30%):   0.116
50% Bioavailability (F50%):   0.988

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.058 MRP1:   0.941
Plasma Protein Binding (PPB):   96.651% Volume Distribution (VD):   -0.526
Fu: 2.756%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.392
OATP1B3 inhibitor:   0.985 BCRP inhibitor:   0.985
BSEP inhibitor:   0.992

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.2
CYP2C19-inhibitor:   0.655 CYP2C19-substrate:   0.529
CYP2C9-inhibitor:   0.832 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.996 CYP2D6-substrate:   0.997
CYP3A4-inhibitor:   0.488 CYP3A4-substrate:   0.002
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.97
HLM stability:   0.911
?
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):  4.064 Half-life (T1/2):  1.149

ADMET: Toxicity

hERG Blockers:  0.081 hERG Blockers (10um):  0.509
Human Hepatotoxicity (H-HT):  0.429 Drug-induced Liver Injury (DILI):  0.628
AMES Toxicity:  0.343 Rat Oral Acute Toxicity:  0.375
Maximum Recommended Daily Dose:  0.422 Skin Sensitization:  0.649
Carcinogencity:  0.731 Eye Corrosion:  0.506
Eye Irritation:  0.957 Respiratory Toxicity:  0.642
Drug-induced Neurotoxicity:  0.283 Ototoxicity:  0.219
Hematotoxicity:  0.332 Drug-induced Nephrotoxicity:  0.163
Genotoxicity:  0.249 RPMI-8226 Immunitoxicity:  0.121
A549 Cytotoxicity:  0.217 Hek293 Cytotoxicity:  0.361
BCF:   1.283
?
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:   3.446
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.491
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.862
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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
NPO32817 gardenia oudiepe Species Rubiaceae Eukaryota flowering buds and leaf bases Foret Plate, New Caledonia n.a. PMID[25659770]
NPO32456 gardenia urvillei Species Rubiaceae Eukaryota flowering buds and leaf bases Noumea, New Caledonia n.a. PMID[25659770]
NPO32817 gardenia oudiepe Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[29207340]

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
NPT1310 Individual protein Xanthine dehydrogenase Bos taurus IC50 = 4540.0 nM PMID[29207340]
NPT518 Protein complex Tubulin Homo sapiens IC50 = 21400.0 nM PMID[9873651]
NPT518 Protein complex Tubulin Homo sapiens Inhibition = 69.9 % PMID[12762820]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT839 Cell line L6 Rattus norvegicus Activity = 78.2 % PMID[17477518]
NPT839 Cell line L6 Rattus norvegicus Activity = 96.1 % PMID[23474387]
NPT319 Cell line B16 Mus musculus IC50 = 91200.0 nM PMID[18458131]
NPT1225 Organism Plasmodium falciparum (isolate FcB1 / Columbia) Plasmodium falciparum FcB1/Columbia GI = 13.2 % PMID[1965654]
NPT2229 Organism Trypanosoma brucei gambiense Trypanosoma brucei gambiense GI = 38.1 % PMID[10869194]
NPT2229 Organism Trypanosoma brucei gambiense Trypanosoma brucei gambiense GI = 42.9 % DOI[10.1016/0960-894X(96)00095-9]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 12.5 uM PMID[25659770]
NPT634 Organism Leishmania amazonensis Leishmania amazonensis IC50 = 9650.0 nM DrugMatrix in vitro pharmacology data

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 NPC472438 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
0.8039 Intermediate Similarity NPC115798
0.8039 Intermediate Similarity NPC29841
0.7451 Intermediate Similarity NPC203891
0.7451 Intermediate Similarity NPC266960
0.7308 Intermediate Similarity NPC163524
0.7308 Intermediate Similarity NPC610359
0.7255 Intermediate Similarity NPC607530
0.717 Intermediate Similarity NPC9609
0.6667 Remote Similarity NPC76376
0.6604 Remote Similarity NPC7973
0.6471 Remote Similarity NPC181250
0.6441 Remote Similarity NPC246478
0.6034 Remote Similarity NPC162351
0.5893 Remote Similarity NPC123886
0.5862 Remote Similarity NPC176300
0.5862 Remote Similarity NPC255350
0.5846 Remote Similarity NPC470459
0.5821 Remote Similarity NPC470457
0.5763 Remote Similarity NPC603596
0.5714 Remote Similarity NPC26227
0.5672 Remote Similarity NPC158761
0.5667 Remote Similarity NPC261004
0.5636 Remote Similarity NPC602291
0.5614 Remote Similarity NPC284552
0.5614 Remote Similarity NPC44079
0.5614 Remote Similarity NPC98661
0.5517 Remote Similarity NPC110070
0.5517 Remote Similarity NPC101830
0.55 Remote Similarity NPC25495
0.55 Remote Similarity NPC78302
0.55 Remote Similarity NPC235215
0.55 Remote Similarity NPC206604
0.5493 Remote Similarity NPC470456
0.5439 Remote Similarity NPC293183
0.5424 Remote Similarity NPC18772
0.541 Remote Similarity NPC279989
0.5397 Remote Similarity NPC76482
0.5352 Remote Similarity NPC470462
0.5345 Remote Similarity NPC241498
0.5345 Remote Similarity NPC219330
0.5345 Remote Similarity NPC184536
0.5345 Remote Similarity NPC156222
0.5345 Remote Similarity NPC103342
0.5333 Remote Similarity NPC82325
0.5333 Remote Similarity NPC83508
0.5254 Remote Similarity NPC100887
0.5254 Remote Similarity NPC286342
0.5254 Remote Similarity NPC214138
0.5254 Remote Similarity NPC59951
0.5254 Remote Similarity NPC62536
0.5246 Remote Similarity NPC236769
0.5246 Remote Similarity NPC7846
0.5172 Remote Similarity NPC259058
0.5167 Remote Similarity NPC256283
0.5082 Remote Similarity NPC604677
0.5075 Remote Similarity NPC213622
0.5068 Remote Similarity NPC305811
0.5068 Remote Similarity NPC488080
0.5068 Remote Similarity NPC169977
0.5067 Remote Similarity NPC101026
0.5067 Remote Similarity NPC488077

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC472438 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
0.5862 Remote Similarity NPD2801 Pre-clinical

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