Natural Product: NPC489677

Natural Product IDNPC489677
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 TVVNXCQSQGSPEY-BMUFGWLNSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 44518134
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001550] Sesquiterpenoids

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 TVVNXCQSQGSPEY-BMUFGWLNSA-N
Standard InCHI InChI=1S/C21H32O4/c1-14-7-6-11-20(3)18(25-20)13-16(15(2)19(22)23-5)10-12-21(4)17(24-21)9-8-14/h7,16-18H,2,6,8-13H2,1,3-5H3/b14-7+/t16-,17+,18-,20+,21+/m0/s1
SMILES C/C/1=CCC[C@]2(C)[C@H](C[C@H](CC[C@]3(C)[C@@H](CC1)O3)C(=C)C(=O)OC)O2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   348.23 Volume:   373.354
?
Van der Waals volume.
Dense:   0.933 LogP:   3.644
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.354
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.821
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   20.0
TPSA:   51.36
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.322 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.905 Fsp3:   0.762
MCE-18:   55.622
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.538 Fluc inhibitor:   0.006
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.005
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.041
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.805 Promiscuous compounds:   0.492

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.692 MDCK Permeability:   -4.805
Pgp-inhibitor:   0.98 Pgp-substrate:   0.0
PAMPA:   0.028
?
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%):   0.097 30% Bioavailability (F30%):   0.242
50% Bioavailability (F50%):   0.941

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.007 MRP1:   0.787
Plasma Protein Binding (PPB):   94.767% Volume Distribution (VD):   0.441
Fu: 5.155%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.404
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.542 CYP1A2-substrate:   0.113
CYP2C19-inhibitor:   0.994 CYP2C19-substrate:   0.015
CYP2C9-inhibitor:   0.213 CYP2C9-substrate:   0.042
CYP2D6-inhibitor:   0.985 CYP2D6-substrate:   0.376
CYP3A4-inhibitor:   0.439 CYP3A4-substrate:   0.171
CYP2B6-substrate:   0.131 CYP2C8-inhibitor:   0.569
HLM stability:   0.776
?
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):  11.798 Half-life (T1/2):  1.324

ADMET: Toxicity

hERG Blockers:  0.117 hERG Blockers (10um):  0.206
Human Hepatotoxicity (H-HT):  0.514 Drug-induced Liver Injury (DILI):  0.431
AMES Toxicity:  0.246 Rat Oral Acute Toxicity:  0.311
Maximum Recommended Daily Dose:  0.582 Skin Sensitization:  0.978
Carcinogencity:  0.658 Eye Corrosion:  0.187
Eye Irritation:  0.973 Respiratory Toxicity:  0.381
Drug-induced Neurotoxicity:  0.186 Ototoxicity:  0.285
Hematotoxicity:  0.221 Drug-induced Nephrotoxicity:  0.327
Genotoxicity:  0.04 RPMI-8226 Immunitoxicity:  0.055
A549 Cytotoxicity:  0.027 Hek293 Cytotoxicity:  0.271
BCF:   2.126
?
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:   4.2
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.587
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.106
?
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
NPO3821 Sinularia flexibilis Species Alcyoniidae Eukaryota n.a. chinese soft coral n.a. PMID[18553926]
NPO3821 Sinularia flexibilis Species Alcyoniidae Eukaryota n.a. n.a. n.a. PMID[30528697]
NPO3821 Sinularia flexibilis Species Alcyoniidae Eukaryota n.a. n.a. n.a. PMID[9644083]
NPO3821 Sinularia flexibilis Species Alcyoniidae Eukaryota n.a. n.a. n.a. Database[COCONUT]

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
NPT113 Cell line RAW264.7 Mus musculus IC50 = 4200.0 nM PMID[30528697]
NPT113 Cell line RAW264.7 Mus musculus Ratio CC50/IC50 > 11.9 n.a. PMID[30528697]
NPT81 Cell line A549 Homo sapiens IC50 > 50000.0 nM PMID[30528697]
NPT139 Cell line HT-29 Homo sapiens IC50 > 50000.0 nM PMID[30528697]
NPT4783 Cell line SNU-398 Homo sapiens IC50 > 50000.0 nM PMID[30528697]
NPT2309 Cell line CAPAN-1 Homo sapiens IC50 > 50000.0 nM PMID[30528697]
NPT113 Cell line RAW264.7 Mus musculus CC50 > 50000.0 nM PMID[30528697]

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 NPC489677 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
0.7959 Intermediate Similarity NPC605615
0.7736 Intermediate Similarity NPC157416
0.766 Intermediate Similarity NPC56419
0.661 Remote Similarity NPC63556
0.6491 Remote Similarity NPC244841
0.6441 Remote Similarity NPC72464
0.6271 Remote Similarity NPC281516
0.5882 Remote Similarity NPC223604
0.5714 Remote Similarity NPC475310
0.5636 Remote Similarity NPC257358
0.5636 Remote Similarity NPC474472
0.5593 Remote Similarity NPC269841
0.5536 Remote Similarity NPC261398
0.5373 Remote Similarity NPC489675
0.5373 Remote Similarity NPC489676
0.5357 Remote Similarity NPC480697
0.5357 Remote Similarity NPC607125
0.5263 Remote Similarity NPC276290
0.5254 Remote Similarity NPC272814
0.5172 Remote Similarity NPC259299
0.5161 Remote Similarity NPC329857
0.5161 Remote Similarity NPC469718
0.5102 Remote Similarity NPC605727
0.5091 Remote Similarity NPC127824
0.5088 Remote Similarity NPC256273
0.5082 Remote Similarity NPC474981
0.5079 Remote Similarity NPC482125
0.5079 Remote Similarity NPC482124

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC489677 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