Natural Product: NPC603859

Natural Product IDNPC603859
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 GDQXJMLXEYSICD-LJQANCHMSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL4168752
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]

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 GDQXJMLXEYSICD-LJQANCHMSA-N
Standard InCHI InChI=1S/C25H22O6/c1-12(2)9-19-21-22(28)20-16(27)11-18-15(7-8-25(3,4)31-18)23(20)30-24(21)14-6-5-13(26)10-17(14)29-19/h5-11,19,26-27H,1-4H3/t19-/m1/s1
SMILES CC(C)=C[C@H]1Oc2cc(O)ccc2-c2oc3c4c(cc(O)c3c(=O)c21)OC(C)(C)C=C4

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   418.14 Volume:   424.551
?
Van der Waals volume.
Dense:   0.985 LogP:   5.408
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.846
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.885
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   28.0
TPSA:   89.13
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   2.0 Rings:   5.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.511 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.944 Fsp3:   0.24
MCE-18:   97.0
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.909 Fluc inhibitor:   0.784
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.78
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.648
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.289 Promiscuous compounds:   0.271

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.947 MDCK Permeability:   -4.698
Pgp-inhibitor:   0.441 Pgp-substrate:   0.289
PAMPA:   0.462
?
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%):   0.98 30% Bioavailability (F30%):   0.999
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.079 MRP1:   0.946
Plasma Protein Binding (PPB):   95.936% Volume Distribution (VD):   0.377
Fu: 4.343%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.819 BCRP inhibitor:   0.914
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.999
CYP2C19-inhibitor:   0.735 CYP2C19-substrate:   0.918
CYP2C9-inhibitor:   0.052 CYP2C9-substrate:   0.822
CYP2D6-inhibitor:   0.036 CYP2D6-substrate:   0.933
CYP3A4-inhibitor:   0.024 CYP3A4-substrate:   0.996
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.999
?
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):  3.644 Half-life (T1/2):  1.614

ADMET: Toxicity

hERG Blockers:  0.116 hERG Blockers (10um):  0.511
Human Hepatotoxicity (H-HT):  0.743 Drug-induced Liver Injury (DILI):  0.952
AMES Toxicity:  0.786 Rat Oral Acute Toxicity:  0.773
Maximum Recommended Daily Dose:  0.868 Skin Sensitization:  0.899
Carcinogencity:  0.872 Eye Corrosion:  0.001
Eye Irritation:  0.864 Respiratory Toxicity:  0.787
Drug-induced Neurotoxicity:  0.167 Ototoxicity:  0.265
Hematotoxicity:  0.161 Drug-induced Nephrotoxicity:  0.197
Genotoxicity:  0.936 RPMI-8226 Immunitoxicity:  0.131
A549 Cytotoxicity:  0.222 Hek293 Cytotoxicity:  0.709
BCF:   1.805
?
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:   4.608
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.484
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.706
?
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
NPO8171 Artocarpus altilis Species Moraceae Eukaryota bud covers n.a. n.a. PMID[11975520]
NPO8171 Artocarpus altilis Species Moraceae Eukaryota n.a. root n.a. PMID[12662107]
NPO2376 Artocarpus elasticus Species Moraceae Eukaryota roots Ping-Tung Hsien, Taiwan 2002-AUG PMID[16309328]
NPO33150 Artocarpus communis Species Moraceae Eukaryota heartwood n.a. n.a. PMID[16643064]
NPO11796 Morus australis Species Moraceae Eukaryota n.a. root n.a. PMID[17405024]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. n.a. n.a. PMID[20815207]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. leaf n.a. PMID[21319773]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. root n.a. PMID[21319773]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. bark n.a. PMID[21319773]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. leaf n.a. PMID[22207282]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. root n.a. PMID[23806866]
NPO28265 Morus alba Species Moraceae Eukaryota root bark University of Veterinary and Pharmaceutical Sciences Brno (UVPS Brno), Brno, Czech Republic 2011-APR PMID[24901948]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. Konya, Turkey 2007-APR PMID[24901948]
NPO33150 Artocarpus communis Species Moraceae Eukaryota roots Khon Kaen, Thailand 2009-DEC PMID[25537111]
NPO28265 Morus alba Species Moraceae Eukaryota leaves Chungbuk, Korea n.a. PMID[25935644]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. root n.a. PMID[25981820]
NPO33150 Artocarpus communis Species Moraceae Eukaryota n.a. n.a. n.a. PMID[26178912]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. latex n.a. PMID[27294120]
NPO11796 Morus australis Species Moraceae Eukaryota Root Bark n.a. n.a. PMID[27908762]
NPO28265 Morus alba Species Moraceae Eukaryota Root barks n.a. n.a. PMID[3097265]
NPO11796 Morus australis Species Moraceae Eukaryota n.a. n.a. n.a. PMID[9358644]
NPO2376 Artocarpus elasticus Species Moraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8171 Artocarpus altilis Species Moraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11796 Morus australis Species Moraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO33150 Artocarpus communis Species Moraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8171 Artocarpus altilis Species Moraceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO8171 Artocarpus altilis Species Moraceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO8171 Artocarpus altilis Species Moraceae Eukaryota n.a. n.a. Database[FooDB]
NPO8171 Artocarpus altilis Species Moraceae Eukaryota n.a. n.a. Database[FooDB]
NPO11796 Morus australis Species Moraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8171 Artocarpus altilis Species Moraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11796 Morus australis Species Moraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO2376 Artocarpus elasticus Species Moraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8171 Artocarpus altilis Species Moraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11796 Morus australis Species Moraceae 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
NPT1464 Individual protein Phosphodiesterase 4D Homo sapiens Inhibition n.a. n.a. % PMID[29291443]
NPT273 Individual protein Phosphodiesterase 5A Homo sapiens IC50 = 410.0 nM PMID[29291443]
NPT1464 Individual protein Phosphodiesterase 4D Homo sapiens IC50 = 5.4 nM PMID[29291443]
NPT4736 Individual protein Phosphodiesterase 9A Homo sapiens IC50 = 350.0 nM PMID[29291443]
NPT5106 Individual protein Phosphodiesterase 10A Homo sapiens IC50 = 510.0 nM PMID[29291443]
NPT27625 Single protein Phosphodiesterase 1B Homo sapiens IC50 = 300.0 nM PMID[29291443]
NPT5100 Individual protein Phosphodiesterase 2A Homo sapiens IC50 = 590.0 nM PMID[29291443]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT28438 Unchecked Unchecked n.a. Ratio IC50 = 76.0 n.a. PMID[29291443]
NPT28438 Unchecked Unchecked n.a. Ratio IC50 = 65.0 n.a. PMID[29291443]
NPT28438 Unchecked Unchecked n.a. Ratio IC50 = 109.0 n.a. PMID[29291443]
NPT28438 Unchecked Unchecked n.a. Ratio IC50 = 55.0 n.a. PMID[29291443]
NPT28438 Unchecked Unchecked n.a. Ratio IC50 = 94.0 n.a. PMID[29291443]

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 NPC603859 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 NPC189087
0.8026 Intermediate Similarity NPC600012
0.7089 Intermediate Similarity NPC321623
0.6386 Remote Similarity NPC478514
0.6145 Remote Similarity NPC62840
0.5897 Remote Similarity NPC166757
0.5833 Remote Similarity NPC476088
0.5769 Remote Similarity NPC293852
0.5696 Remote Similarity NPC599988
0.5632 Remote Similarity NPC217083
0.5618 Remote Similarity NPC478515
0.5581 Remote Similarity NPC276444
0.5568 Remote Similarity NPC194427
0.5542 Remote Similarity NPC319752
0.5309 Remote Similarity NPC170492
0.5281 Remote Similarity NPC475805
0.525 Remote Similarity NPC24673
0.5165 Remote Similarity NPC198829
0.506 Remote Similarity NPC608191
0.5055 Remote Similarity NPC156432

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC603859 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