Natural Product: NPC601961

Natural Product IDNPC601961
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 FVDBKWBFRSVIAW-UJXSZHEFSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL487605
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 FVDBKWBFRSVIAW-UJXSZHEFSA-N
Standard InCHI InChI=1S/C20H34O2/c1-16(2)8-6-10-18(4)14-20(22)15-19(5)11-7-9-17(3)12-13-21/h8,11-12,14,20-22H,6-7,9-10,13,15H2,1-5H3/b17-12+,18-14+,19-11+/t20-/m0/s1
SMILES CC(C)=CCC/C(C)=C/[C@H](O)C/C(C)=C/CC/C(C)=C/CO

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   306.26 Volume:   361.511
?
Van der Waals volume.
Dense:   0.847 LogP:   4.487
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.341
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.849
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   10.0 Rigid Bonds:   4.0
TPSA:   40.46
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   2.0 Rings:   0.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.552 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.632 Fsp3:   0.6
MCE-18:   5.0
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.427 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.001
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.0
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.839 Promiscuous compounds:   0.169

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.576 MDCK Permeability:   -4.849
Pgp-inhibitor:   0.994 Pgp-substrate:   0.0
PAMPA:   0.027
?
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):   0.554
20% Bioavailability (F20%):   0.038 30% Bioavailability (F30%):   0.203
50% Bioavailability (F50%):   0.928

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.005 MRP1:   0.696
Plasma Protein Binding (PPB):   76.168% Volume Distribution (VD):   -0.271
Fu: 20.452%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.0
BSEP inhibitor:   0.734

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.128 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.003 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.172 CYP2D6-substrate:   0.061
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.001
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.0
HLM stability:   0.963
?
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):  10.821 Half-life (T1/2):  1.232

ADMET: Toxicity

hERG Blockers:  0.068 hERG Blockers (10um):  0.337
Human Hepatotoxicity (H-HT):  0.85 Drug-induced Liver Injury (DILI):  0.238
AMES Toxicity:  0.177 Rat Oral Acute Toxicity:  0.207
Maximum Recommended Daily Dose:  0.344 Skin Sensitization:  0.996
Carcinogencity:  0.461 Eye Corrosion:  0.068
Eye Irritation:  0.914 Respiratory Toxicity:  0.938
Drug-induced Neurotoxicity:  0.723 Ototoxicity:  0.662
Hematotoxicity:  0.679 Drug-induced Nephrotoxicity:  0.702
Genotoxicity:  0.087 RPMI-8226 Immunitoxicity:  0.102
A549 Cytotoxicity:  0.513 Hek293 Cytotoxicity:  0.166
BCF:   2.272
?
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:   4.933
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.282
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.827
?
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
NPO8863 Cystoseira crinita Species Sargassaceae Eukaryota n.a. n.a. n.a. PMID[12880316]
NPO8863 Cystoseira crinita Species Sargassaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8863 Cystoseira crinita Species Sargassaceae 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
NPT878 Organism Streptococcus mutans Streptococcus mutans MIC = 12.5 ug.mL-1 PMID[1522419]
NPT878 Organism Streptococcus mutans Streptococcus mutans Ratio = 64.0 n.a. PMID[1522419]
NPT878 Organism Streptococcus mutans Streptococcus mutans MIC = 0.78 ug.mL-1 PMID[1522419]
NPT878 Organism Streptococcus mutans Streptococcus mutans MIC = 50.0 ug.mL-1 PMID[1522419]
NPT878 Organism Streptococcus mutans Streptococcus mutans Activity n.a. n.a. n.a. DOI[10.1021/np50124a023]
NPT79 Organism Bacillus subtilis Bacillus subtilis MIC = 12.5 ug.mL-1 PMID[1522419]
NPT79 Organism Bacillus subtilis Bacillus subtilis MIC = 50.0 ug.mL-1 PMID[1522419]
NPT79 Organism Bacillus subtilis Bacillus subtilis Activity n.a. n.a. n.a. DOI[10.1021/np50124a023]
NPT79 Organism Bacillus subtilis Bacillus subtilis Ratio = 2.0 n.a. PMID[1522419]
NPT2539 Organism Corynebacterium ammoniagenes Corynebacterium ammoniagenes Ratio = 2.0 n.a. PMID[1522419]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 400.0 ug.mL-1 PMID[1522419]
NPT2539 Organism Corynebacterium ammoniagenes Corynebacterium ammoniagenes MIC = 100.0 ug.mL-1 PMID[1522419]
NPT2539 Organism Corynebacterium ammoniagenes Corynebacterium ammoniagenes MIC = 50.0 ug.mL-1 PMID[1522419]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus Activity n.a. n.a. n.a. DOI[10.1021/np50124a023]
NPT2539 Organism Corynebacterium ammoniagenes Corynebacterium ammoniagenes Activity n.a. n.a. n.a. DOI[10.1021/np50124a023]
NPT29275 Organism Cutibacterium acnes Cutibacterium acnes Ratio = 2.0 n.a. PMID[1522419]
NPT29275 Organism Cutibacterium acnes Cutibacterium acnes MIC = 25.0 ug.mL-1 PMID[1522419]
NPT29275 Organism Cutibacterium acnes Cutibacterium acnes MIC = 25.0 ug.mL-1 PMID[8158169]
NPT29275 Organism Cutibacterium acnes Cutibacterium acnes MIC = 6.25 ug.mL-1 PMID[1522419]
NPT29275 Organism Cutibacterium acnes Cutibacterium acnes Activity n.a. n.a. n.a. DOI[10.1021/np50124a023]

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 NPC601961 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
0.8438 Intermediate Similarity NPC604226
0.6774 Remote Similarity NPC29091
0.6774 Remote Similarity NPC103213
0.6774 Remote Similarity NPC300623
0.6774 Remote Similarity NPC213538
0.6774 Remote Similarity NPC269823
0.6774 Remote Similarity NPC39222
0.6774 Remote Similarity NPC9860
0.6667 Remote Similarity NPC182840
0.6667 Remote Similarity NPC255042
0.5833 Remote Similarity NPC140501
0.575 Remote Similarity NPC329686
0.5429 Remote Similarity NPC116934
0.5106 Remote Similarity NPC471061

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC601961 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
0.5833 Remote Similarity NPD4265 Phase 2

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