Natural Product: NPC138489

Natural Product IDNPC138489
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 YDDGKXBLOXEEMN-WOJBJXKFSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 65018
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000264] Organic acids and derivatives
      • [CHEMONTID:0000265] Carboxylic acids and derivatives
        • [CHEMONTID:0002966] Tetracarboxylic acids and derivatives

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 YDDGKXBLOXEEMN-WOJBJXKFSA-N
Standard InCHI InChI=1S/C22H18O12/c23-13-5-1-11(9-15(13)25)3-7-17(27)33-19(21(29)30)20(22(31)32)34-18(28)8-4-12-2-6-14(24)16(26)10-12/h1-10,19-20,23-26H,(H,29,30)(H,31,32)/t19-,20-/m1/s1
SMILES c1cc(c(cc1C=CC(=O)O[C@H]([C@H](C(=O)O)OC(=O)C=Cc1ccc(c(c1)O)O)C(=O)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   474.08 Volume:   445.8
?
Van der Waals volume.
Dense:   1.063 LogP:   1.241
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.521
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.276
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   11.0 Rigid Bonds:   18.0
TPSA:   208.12
?
Topological Polar Surface Area.
 H-Bond Acceptor:   12.0
H-Bond Donor:   6.0 Rings:   2.0
Heavy Atoms:   12.0

MedChem Properties

QED Drug-Likeness Score:   0.172 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.514 Fsp3:   0.091
MCE-18:   36.0
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Accepted
Pfizer Rule:   Rejected GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   1
Colloidal aggregators:   0.825 Fluc inhibitor:   1.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.083
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.541
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.673 Promiscuous compounds:   0.518

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.909 MDCK Permeability:   -4.964
Pgp-inhibitor:   0.0 Pgp-substrate:   0.0
PAMPA:   1.0
?
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):   0.756
20% Bioavailability (F20%):   1.0 30% Bioavailability (F30%):   1.0
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.879
Plasma Protein Binding (PPB):   76.564% Volume Distribution (VD):   -0.345
Fu: 14.312%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.0
BSEP inhibitor:   0.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.004 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.004 CYP2D6-substrate:   0.794
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.994
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.944
HLM stability:   0.274
?
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):  7.054 Half-life (T1/2):  1.9

ADMET: Toxicity

hERG Blockers:  0.019 hERG Blockers (10um):  0.056
Human Hepatotoxicity (H-HT):  0.364 Drug-induced Liver Injury (DILI):  0.882
AMES Toxicity:  0.375 Rat Oral Acute Toxicity:  0.047
Maximum Recommended Daily Dose:  0.242 Skin Sensitization:  1.0
Carcinogencity:  0.066 Eye Corrosion:  0.511
Eye Irritation:  0.991 Respiratory Toxicity:  0.251
Drug-induced Neurotoxicity:  0.011 Ototoxicity:  0.803
Hematotoxicity:  0.029 Drug-induced Nephrotoxicity:  0.908
Genotoxicity:  0.621 RPMI-8226 Immunitoxicity:  0.005
A549 Cytotoxicity:  0.367 Hek293 Cytotoxicity:  0.031
BCF:   0.776
?
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:   3.645
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.654
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.442
?
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
NPO9865 Cichorium intybus Species Asteraceae Eukaryota n.a. n.a. n.a. DOI[10.1007/s11627-001-0052-8]
NPO9865 Cichorium intybus Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[18341288]
NPO9865 Cichorium intybus Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[18460139]
NPO8002 Solanum olgae Species Solanaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9865 Cichorium intybus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29531 Lupinus cosentinii Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO513 Agathosma scaberula Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13123 Balanophora harlandii Species Balanophoraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO245 Euphorbia biglandulosa Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17549 Polemonium caeruleum Species Polemoniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2161 Strychnos ledermannii Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1584 Tolypothrix tjipanasensis Species Tolypothrichaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO4892 Viburnum davidii Species Adoxaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10756 Callitris drummondii Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4787 Capuronianthus mahafalensis Species Meliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1854 Cardiospermum hirsutum Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9865 Cichorium intybus Species Asteraceae Eukaryota Roots n.a. Database[FooDB]
NPO9865 Cichorium intybus Species Asteraceae Eukaryota Root n.a. n.a. Database[FooDB]
NPO9865 Cichorium intybus Species Asteraceae Eukaryota n.a. n.a. Database[FooDB]
NPO9865 Cichorium intybus Species Asteraceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO9865 Cichorium intybus Species Asteraceae Eukaryota Flower n.a. n.a. Database[FooDB]
NPO1854 Cardiospermum hirsutum Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO9865 Cichorium intybus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO9865 Cichorium intybus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[MetaboLights]
NPO9865 Cichorium intybus Species Asteraceae Eukaryota n.a. n.a. Database[Phenol-Explorer]
NPO1854 Cardiospermum hirsutum Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO9865 Cichorium intybus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO9865 Cichorium intybus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO9865 Cichorium intybus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO245 Euphorbia biglandulosa Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2161 Strychnos ledermannii Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9865 Cichorium intybus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29531 Lupinus cosentinii Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13123 Balanophora harlandii Species Balanophoraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1584 Tolypothrix tjipanasensis Species Tolypothrichaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO8002 Solanum olgae Species Solanaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17549 Polemonium caeruleum Species Polemoniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4892 Viburnum davidii Species Adoxaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4787 Capuronianthus mahafalensis Species Meliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10756 Callitris drummondii Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1854 Cardiospermum hirsutum Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO513 Agathosma scaberula Species Rutaceae 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

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 NPC138489 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
1.0 High Similarity NPC217052
1.0 High Similarity NPC329344
1.0 High Similarity NPC237506
1.0 High Similarity NPC32626
0.8 Intermediate Similarity NPC132921
0.7826 Intermediate Similarity NPC251407
0.7826 Intermediate Similarity NPC168653
0.75 Intermediate Similarity NPC18074
0.75 Intermediate Similarity NPC5419
0.75 Intermediate Similarity NPC25581
0.75 Intermediate Similarity NPC61
0.6792 Remote Similarity NPC179505
0.6585 Remote Similarity NPC226250
0.6545 Remote Similarity NPC67349
0.6545 Remote Similarity NPC279676
0.6538 Remote Similarity NPC198388
0.6429 Remote Similarity NPC289690
0.64 Remote Similarity NPC488563
0.6136 Remote Similarity NPC95381
0.5965 Remote Similarity NPC156709
0.5965 Remote Similarity NPC477333
0.5926 Remote Similarity NPC475695
0.5833 Remote Similarity NPC275519
0.5818 Remote Similarity NPC13818
0.5818 Remote Similarity NPC219428
0.5763 Remote Similarity NPC477334
0.5745 Remote Similarity NPC217472
0.5745 Remote Similarity NPC150610
0.5667 Remote Similarity NPC38473
0.5636 Remote Similarity NPC610418
0.5593 Remote Similarity NPC206095
0.5593 Remote Similarity NPC35702
0.5593 Remote Similarity NPC224389
0.5536 Remote Similarity NPC108553
0.5517 Remote Similarity NPC319628
0.551 Remote Similarity NPC233669
0.551 Remote Similarity NPC261453
0.551 Remote Similarity NPC474967
0.551 Remote Similarity NPC33749
0.5484 Remote Similarity NPC221383
0.5469 Remote Similarity NPC160378
0.5424 Remote Similarity NPC471027
0.5424 Remote Similarity NPC37250
0.5424 Remote Similarity NPC142703
0.5424 Remote Similarity NPC152942
0.5424 Remote Similarity NPC9991
0.5424 Remote Similarity NPC302857
0.5424 Remote Similarity NPC600892
0.54 Remote Similarity NPC147654
0.54 Remote Similarity NPC281277
0.5312 Remote Similarity NPC283081
0.5294 Remote Similarity NPC328593
0.5294 Remote Similarity NPC474275
0.5294 Remote Similarity NPC147192
0.5294 Remote Similarity NPC309434
0.5294 Remote Similarity NPC224208
0.5294 Remote Similarity NPC41661
0.5238 Remote Similarity NPC19149
0.5238 Remote Similarity NPC477335
0.5227 Remote Similarity NPC1075
0.5227 Remote Similarity NPC1786
0.5227 Remote Similarity NPC294902
0.5192 Remote Similarity NPC263386
0.5192 Remote Similarity NPC141791
0.5161 Remote Similarity NPC284948
0.5161 Remote Similarity NPC303090
0.5161 Remote Similarity NPC301382
0.5161 Remote Similarity NPC37331
0.5156 Remote Similarity NPC143892
0.5156 Remote Similarity NPC299090
0.5156 Remote Similarity NPC246566
0.5094 Remote Similarity NPC203124
0.5094 Remote Similarity NPC607366
0.5077 Remote Similarity NPC481155
0.5077 Remote Similarity NPC322660

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC138489 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
0.5161 Remote Similarity NPD6190 Approved

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