Natural Product: NPC488498

Natural Product IDNPC488498
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 QYCOHMYDSOZCQD-VFKWDGSMSA-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 QYCOHMYDSOZCQD-VFKWDGSMSA-N
Standard InCHI InChI=1S/C20H30O4/c1-13(12-17(21)22)6-8-15-14(2)7-9-16-19(15,3)10-5-11-20(16,4)18(23)24/h12,15-16H,2,5-11H2,1,3-4H3,(H,21,22)(H,23,24)/b13-12-/t15-,16+,19+,20+/m0/s1
SMILES C/C(=C/C(=O)O)/CC[C@H]1C(=C)CC[C@@H]2[C@]1(C)CCC[C@@]2(C)C(=O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   334.21 Volume:   361.978
?
Van der Waals volume.
Dense:   0.923 LogP:   3.705
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.856
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.784
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   15.0
TPSA:   74.6
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.566 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.082 Fsp3:   0.7
MCE-18:   45.529
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.144 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.003
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.002
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.861 Promiscuous compounds:   0.138

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.084 MDCK Permeability:   -4.938
Pgp-inhibitor:   0.0 Pgp-substrate:   0.0
PAMPA:   0.958
?
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):   0.0
20% Bioavailability (F20%):   0.002 30% Bioavailability (F30%):   0.0
50% Bioavailability (F50%):   0.006

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.998
Plasma Protein Binding (PPB):   95.169% Volume Distribution (VD):   -0.582
Fu: 6.599%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.997
OATP1B3 inhibitor:   0.969 BCRP inhibitor:   0.0
BSEP inhibitor:   0.807

ADMET: Metabolism

CYP1A2-inhibitor:   0.415 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.268 CYP2C19-substrate:   0.003
CYP2C9-inhibitor:   0.835 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.888 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.058 CYP2C8-inhibitor:   0.291
HLM stability:   0.004
?
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):  0.869 Half-life (T1/2):  1.176

ADMET: Toxicity

hERG Blockers:  0.008 hERG Blockers (10um):  0.015
Human Hepatotoxicity (H-HT):  0.655 Drug-induced Liver Injury (DILI):  0.328
AMES Toxicity:  0.103 Rat Oral Acute Toxicity:  0.153
Maximum Recommended Daily Dose:  0.194 Skin Sensitization:  0.987
Carcinogencity:  0.456 Eye Corrosion:  0.912
Eye Irritation:  0.986 Respiratory Toxicity:  0.82
Drug-induced Neurotoxicity:  0.028 Ototoxicity:  0.422
Hematotoxicity:  0.272 Drug-induced Nephrotoxicity:  0.93
Genotoxicity:  0.187 RPMI-8226 Immunitoxicity:  0.016
A549 Cytotoxicity:  0.002 Hek293 Cytotoxicity:  0.02
BCF:   0.865
?
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:   3.926
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.391
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.32
?
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
NPO21387 Forsythia suspensa Species Oleaceae Eukaryota n.a. n.a. n.a. PMID[17156960]
NPO21387 Forsythia suspensa Species Oleaceae Eukaryota n.a. n.a. n.a. PMID[26422318]
NPO21387 Forsythia suspensa Species Oleaceae Eukaryota Fruits n.a. n.a. PMID[28218000]
NPO21387 Forsythia suspensa Species Oleaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21387 Forsythia suspensa Species Oleaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21387 Forsythia suspensa Species Oleaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21387 Forsythia suspensa Species Oleaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO21387 Forsythia suspensa Species Oleaceae 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
NPT2740 Cell line Neutrophils n.a. IC50 > 10.0 ug.mL-1 PMID[28218000]

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 NPC488498 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 NPC61952
1.0 High Similarity NPC603184
0.75 Intermediate Similarity NPC481630
0.7347 Intermediate Similarity NPC72343
0.7059 Intermediate Similarity NPC91369
0.7 Intermediate Similarity NPC36616
0.6923 Remote Similarity NPC239098
0.6731 Remote Similarity NPC18819
0.6731 Remote Similarity NPC46610
0.6667 Remote Similarity NPC198240
0.6667 Remote Similarity NPC237591
0.6667 Remote Similarity NPC40228
0.6667 Remote Similarity NPC3753
0.6545 Remote Similarity NPC600691
0.6538 Remote Similarity NPC59436
0.6415 Remote Similarity NPC471159
0.6415 Remote Similarity NPC123880
0.6316 Remote Similarity NPC14203
0.6316 Remote Similarity NPC229584
0.6316 Remote Similarity NPC477782
0.6296 Remote Similarity NPC269543
0.6296 Remote Similarity NPC247783
0.6207 Remote Similarity NPC477783
0.62 Remote Similarity NPC107258
0.5965 Remote Similarity NPC232344
0.5849 Remote Similarity NPC99154
0.5849 Remote Similarity NPC194322
0.5849 Remote Similarity NPC488496
0.5849 Remote Similarity NPC488504
0.5741 Remote Similarity NPC161923
0.5741 Remote Similarity NPC183503
0.5741 Remote Similarity NPC283908
0.5741 Remote Similarity NPC103958
0.5741 Remote Similarity NPC610917
0.5556 Remote Similarity NPC132542
0.5484 Remote Similarity NPC46536
0.5484 Remote Similarity NPC138139
0.5484 Remote Similarity NPC603180
0.537 Remote Similarity NPC330659
0.537 Remote Similarity NPC244708
0.537 Remote Similarity NPC161187
0.5357 Remote Similarity NPC165711
0.5357 Remote Similarity NPC109854
0.5273 Remote Similarity NPC133253
0.5254 Remote Similarity NPC488497
0.5179 Remote Similarity NPC159148
0.5179 Remote Similarity NPC281880
0.5172 Remote Similarity NPC610334

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC488498 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