Natural Product: NPC488303

Natural Product IDNPC488303
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 DZTWAOVNNLDWNH-VWDWFEEISA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
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 DZTWAOVNNLDWNH-VWDWFEEISA-N
Standard InCHI InChI=1S/C20H26O6/c1-6-10(2)18(22)25-15-9-20(5)16(26-20)8-13(21)11(3)7-14-17(15)12(4)19(23)24-14/h6-7,13-17,21H,4,8-9H2,1-3,5H3/b10-6+,11-7-/t13-,14-,15-,16-,17-,20+/m0/s1
SMILES C/C=C(C)/C(=O)O[C@H]1C[C@]2(C)[C@H](C[C@@H](/C(=C[C@H]3[C@@H]1C(=C)C(=O)O3)/C)O)O2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   362.17 Volume:   368.366
?
Van der Waals volume.
Dense:   0.983 LogP:   1.785
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.853
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.119
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   20.0
TPSA:   85.36
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.351 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.208 Fsp3:   0.6
MCE-18:   55.0
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.815 Fluc inhibitor:   0.003
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.058
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.007
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.346 Promiscuous compounds:   0.39

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.915 MDCK Permeability:   -4.687
Pgp-inhibitor:   0.397 Pgp-substrate:   0.877
PAMPA:   0.932
?
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):   0.097
20% Bioavailability (F20%):   0.932 30% Bioavailability (F30%):   0.993
50% Bioavailability (F50%):   0.993

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.048 MRP1:   0.977
Plasma Protein Binding (PPB):   89.953% Volume Distribution (VD):   -0.072
Fu: 10.358%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.992
OATP1B3 inhibitor:   0.945 BCRP inhibitor:   0.02
BSEP inhibitor:   0.955

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.098
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.031
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.007
CYP3A4-inhibitor:   0.473 CYP3A4-substrate:   0.774
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.975
HLM stability:   0.791
?
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):  11.38 Half-life (T1/2):  1.684

ADMET: Toxicity

hERG Blockers:  0.011 hERG Blockers (10um):  0.099
Human Hepatotoxicity (H-HT):  0.608 Drug-induced Liver Injury (DILI):  0.857
AMES Toxicity:  0.747 Rat Oral Acute Toxicity:  0.418
Maximum Recommended Daily Dose:  0.558 Skin Sensitization:  0.997
Carcinogencity:  0.655 Eye Corrosion:  0.049
Eye Irritation:  0.721 Respiratory Toxicity:  0.136
Drug-induced Neurotoxicity:  0.394 Ototoxicity:  0.728
Hematotoxicity:  0.538 Drug-induced Nephrotoxicity:  0.846
Genotoxicity:  0.911 RPMI-8226 Immunitoxicity:  0.155
A549 Cytotoxicity:  0.4 Hek293 Cytotoxicity:  0.249
BCF:   0.552
?
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:   3.24
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.934
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.194
?
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
NPO15440 Chamaemelum nobile Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[23501116]
NPO15440 Chamaemelum nobile Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[24471493]
NPO15440 Chamaemelum nobile Species Asteraceae Eukaryota Flowers n.a. n.a. PMID[28116906]
NPO15440 Chamaemelum nobile Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15440 Chamaemelum nobile Species Asteraceae Eukaryota Flower n.a. n.a. Database[FooDB]
NPO15440 Chamaemelum nobile Species Asteraceae Eukaryota Plant n.a. n.a. Database[FooDB]
NPO15440 Chamaemelum nobile Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15440 Chamaemelum nobile Species Asteraceae 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
NPT839 Cell line L6 Rattus norvegicus IC50 = 5300.0 nM PMID[28116906]
NPT844 Organism Trypanosoma brucei rhodesiense Trypanosoma brucei rhodesiense IC50 = 1200.0 nM PMID[28116906]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum IC50 = 3000.0 nM PMID[28116906]
NPT580 Organism Trypanosoma cruzi Trypanosoma cruzi IC50 = 7300.0 nM PMID[28116906]
NPT633 Organism Leishmania donovani Leishmania donovani IC50 = 2700.0 nM PMID[28116906]
NPT2 Others Unspecified n.a. Ratio IC50 = 4.5 n.a. PMID[28116906]
NPT2 Others Unspecified n.a. Ratio IC50 = 0.7 n.a. PMID[28116906]
NPT2 Others Unspecified n.a. Ratio IC50 = 1.9 n.a. PMID[28116906]
NPT2 Others Unspecified n.a. Ratio IC50 = 1.8 n.a. PMID[28116906]

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 NPC488303 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 NPC475838
1.0 High Similarity NPC125674
1.0 High Similarity NPC228451
0.84 Intermediate Similarity NPC484204
0.7636 Intermediate Similarity NPC474247
0.7321 Intermediate Similarity NPC279621
0.6935 Remote Similarity NPC486038
0.6327 Remote Similarity NPC488299
0.6296 Remote Similarity NPC488302
0.6296 Remote Similarity NPC475461
0.6296 Remote Similarity NPC488300
0.6296 Remote Similarity NPC488301
0.6296 Remote Similarity NPC250940
0.6296 Remote Similarity NPC169575
0.6071 Remote Similarity NPC488298
0.6071 Remote Similarity NPC488297
0.5932 Remote Similarity NPC488304
0.5893 Remote Similarity NPC140543
0.5833 Remote Similarity NPC230800
0.5818 Remote Similarity NPC50637
0.5714 Remote Similarity NPC116543
0.5614 Remote Similarity NPC35498
0.5593 Remote Similarity NPC187268
0.5574 Remote Similarity NPC140591
0.5574 Remote Similarity NPC197835
0.5574 Remote Similarity NPC303653
0.5556 Remote Similarity NPC96018
0.5517 Remote Similarity NPC475855
0.5424 Remote Similarity NPC299396
0.5345 Remote Similarity NPC488296
0.5333 Remote Similarity NPC474338
0.5167 Remote Similarity NPC287089
0.5161 Remote Similarity NPC486031
0.5161 Remote Similarity NPC608924
0.5079 Remote Similarity NPC189609
0.5079 Remote Similarity NPC291500
0.5079 Remote Similarity NPC481910

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC488303 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