Natural Product: NPC302761

Natural Product IDNPC302761
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 LIBLOJFUIMXLIF-FEHMIHBQSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 14658766
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001534] Quinone and hydroquinone lipids
          • [CHEMONTID:0002802] Prenylquinones

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 LIBLOJFUIMXLIF-FEHMIHBQSA-N
Standard InCHI InChI=1S/C21H29NO2/c1-13-6-5-7-18-20(13,3)9-8-14(2)21(18,4)12-15-10-16(23)11-17(22)19(15)24/h6,10-11,14,18H,5,7-9,12,22H2,1-4H3/t14-,18+,20+,21+/m0/s1
SMILES CC1=CCC[C@@H]2[C@]1(C)CC[C@H](C)[C@@]2(C)CC1=CC(=O)C=C(C1=O)N

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   327.22 Volume:   361.498
?
Van der Waals volume.
Dense:   0.905 LogP:   3.313
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.111
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.533
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   19.0
TPSA:   60.16
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.613 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.456 Fsp3:   0.619
MCE-18:   54.353
?
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:   1
Colloidal aggregators:   0.752 Fluc inhibitor:   0.755
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.271
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.045
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.386 Promiscuous compounds:   0.213

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.034 MDCK Permeability:   -4.689
Pgp-inhibitor:   0.051 Pgp-substrate:   0.01
PAMPA:   0.421
?
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%):   0.01 30% Bioavailability (F30%):   0.012
50% Bioavailability (F50%):   0.181

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.419 MRP1:   0.811
Plasma Protein Binding (PPB):   88.89% Volume Distribution (VD):   0.472
Fu: 8.549%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.996
OATP1B3 inhibitor:   0.993 BCRP inhibitor:   0.023
BSEP inhibitor:   0.711

ADMET: Metabolism

CYP1A2-inhibitor:   0.003 CYP1A2-substrate:   0.432
CYP2C19-inhibitor:   0.254 CYP2C19-substrate:   0.003
CYP2C9-inhibitor:   0.009 CYP2C9-substrate:   0.039
CYP2D6-inhibitor:   0.001 CYP2D6-substrate:   0.13
CYP3A4-inhibitor:   0.316 CYP3A4-substrate:   0.999
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.952
HLM stability:   0.734
?
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):  10.241 Half-life (T1/2):  0.704

ADMET: Toxicity

hERG Blockers:  0.061 hERG Blockers (10um):  0.338
Human Hepatotoxicity (H-HT):  0.767 Drug-induced Liver Injury (DILI):  0.506
AMES Toxicity:  0.694 Rat Oral Acute Toxicity:  0.353
Maximum Recommended Daily Dose:  0.74 Skin Sensitization:  0.926
Carcinogencity:  0.94 Eye Corrosion:  0.003
Eye Irritation:  0.818 Respiratory Toxicity:  0.563
Drug-induced Neurotoxicity:  0.657 Ototoxicity:  0.219
Hematotoxicity:  0.735 Drug-induced Nephrotoxicity:  0.456
Genotoxicity:  0.975 RPMI-8226 Immunitoxicity:  0.131
A549 Cytotoxicity:  0.274 Hek293 Cytotoxicity:  0.549
BCF:   2.145
?
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:   4.809
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.19
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.829
?
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
NPO32617 dysidea sp. Species Dysideidae Eukaryota n.a. n.a. n.a. PMID[11374954]
NPO32617 dysidea sp. Species Dysideidae Eukaryota n.a. n.a. n.a. PMID[15921404]
NPO32617 dysidea sp. Species Dysideidae Eukaryota n.a. n.a. n.a. PMID[1593283]
NPO32617 dysidea sp. Species Dysideidae Eukaryota n.a. n.a. n.a. PMID[18198840]
NPO32617 dysidea sp. Species Dysideidae Eukaryota n.a. at 1020 m depth from Chuuk Atoll, Federated States of Micronesia n.a. PMID[18824352]
NPO32617 dysidea sp. Species Dysideidae Eukaryota n.a. n.a. n.a. PMID[20230038]
NPO32617 dysidea sp. Species Dysideidae Eukaryota n.a. n.a. n.a. PMID[26551342]
NPO32617 dysidea sp. Species Dysideidae Eukaryota n.a. n.a. n.a. PMID[26863083]
NPO32617 dysidea sp. Species Dysideidae Eukaryota n.a. n.a. n.a. PMID[27336796]
NPO32617 dysidea sp. Species Dysideidae Eukaryota n.a. n.a. n.a. PMID[32243140]
NPO32617 dysidea sp. Species Dysideidae Eukaryota n.a. Indo-Pacific n.a. PMID[7494145]
NPO32617 dysidea sp. Species Dysideidae Eukaryota n.a. n.a. n.a. PMID[9748373]

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
NPT178 Individual protein Protein-tyrosine phosphatase 1B Homo sapiens IC50 = 18000.0 nM PMID[27336796]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT913 Cell line CHO-K1 Cricetulus griseus IC50 > 30900.0 nM PMID[31253530]
NPT141 Organism Agrobacterium tumefaciens Agrobacterium tumefaciens Inhibition = 53.0 % DOI[10.1021/np50069a027]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 50.0 ug.mL-1 DOI[10.1021/np50069a027]
NPT2 Others Unspecified n.a. IC50 = 13200.0 nM PMID[31253530]
NPT2 Others Unspecified n.a. IC50 = 27500.0 nM PMID[31253530]

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
- Artemia LC50 = 0.24 ppm DOI[10.1021/np50069a027]

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 NPC302761 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
0.6863 Remote Similarity NPC260474
0.6481 Remote Similarity NPC108955
0.6429 Remote Similarity NPC489061
0.625 Remote Similarity NPC602754
0.625 Remote Similarity NPC608337
0.5909 Remote Similarity NPC605940
0.551 Remote Similarity NPC606666
0.5484 Remote Similarity NPC604451
0.5312 Remote Similarity NPC34193
0.5312 Remote Similarity NPC218631
0.5312 Remote Similarity NPC606042
0.5231 Remote Similarity NPC489062
0.5172 Remote Similarity NPC473251
0.5172 Remote Similarity NPC42586
0.5172 Remote Similarity NPC55869
0.507 Remote Similarity NPC601900

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC302761 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