Natural Product: NPC241512

Natural Product IDNPC241512
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 5-Epiilimaquinone
IUPAC Name 3-[[(1R,2S,4aR,8aS)-1,2,4a-trimethyl-5-methylidene-3,4,6,7,8,8a-hexahydro-2H-naphthalen-1-yl]methyl]-2-hydroxy-5-methoxycyclohexa-2,5-diene-1,4-dione
Synonyms 5-Epiilimaquinone
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL521729
PubChem CID 21727418
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 JJWITJNSXCXULM-UPOGBMBOSA-N
Standard InCHI InChI=1S/C22H30O4/c1-13-7-6-8-18-21(13,3)10-9-14(2)22(18,4)12-15-19(24)16(23)11-17(26-5)20(15)25/h11,14,18,24H,1,6-10,12H2,2-5H3/t14-,18+,21-,22+/m0/s1
SMILES COC1=CC(=O)C(=C(C1=O)C[C@]1(C)[C@@H](C)CC[C@@]2([C@H]1CCCC2=C)C)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   358.21 Volume:   385.377
?
Van der Waals volume.
Dense:   0.93 LogP:   3.57
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.429
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.606
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The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   20.0
TPSA:   63.6
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Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.588 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.357 Fsp3:   0.636
MCE-18:   57.5
?
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:   0.537 Fluc inhibitor:   0.702
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.039
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.029
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.645 Promiscuous compounds:   0.278

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.561 MDCK Permeability:   -4.62
Pgp-inhibitor:   0.226 Pgp-substrate:   0.0
PAMPA:   0.149
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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%):   0.008 30% Bioavailability (F30%):   0.06
50% Bioavailability (F50%):   0.814

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.09
Plasma Protein Binding (PPB):   89.647% Volume Distribution (VD):   0.19
Fu: 10.115%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.963
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.979 CYP1A2-substrate:   0.587
CYP2C19-inhibitor:   0.236 CYP2C19-substrate:   0.132
CYP2C9-inhibitor:   0.084 CYP2C9-substrate:   0.005
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.727
CYP3A4-inhibitor:   0.022 CYP3A4-substrate:   0.065
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.826
HLM stability:   0.947
?
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):  2.564 Half-life (T1/2):  1.462

ADMET: Toxicity

hERG Blockers:  0.018 hERG Blockers (10um):  0.087
Human Hepatotoxicity (H-HT):  0.713 Drug-induced Liver Injury (DILI):  0.522
AMES Toxicity:  0.564 Rat Oral Acute Toxicity:  0.237
Maximum Recommended Daily Dose:  0.596 Skin Sensitization:  0.89
Carcinogencity:  0.902 Eye Corrosion:  0.273
Eye Irritation:  0.982 Respiratory Toxicity:  0.768
Drug-induced Neurotoxicity:  0.164 Ototoxicity:  0.229
Hematotoxicity:  0.779 Drug-induced Nephrotoxicity:  0.746
Genotoxicity:  0.368 RPMI-8226 Immunitoxicity:  0.077
A549 Cytotoxicity:  0.104 Hek293 Cytotoxicity:  0.297
BCF:   2.316
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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:   5.135
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.765
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.457
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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
NPO32618 Hyrtios Genus Thorectidae Eukaryota n.a. n.a. n.a. PMID[10785412]
NPO25355 Dactylospongia elegans Species Thorectidae Eukaryota n.a. n.a. n.a. PMID[10978215]
NPO25355 Dactylospongia elegans Species Thorectidae Eukaryota n.a. n.a. n.a. PMID[12542344]
NPO25355 Dactylospongia elegans Species Thorectidae Eukaryota n.a. n.a. n.a. PMID[21155589]
NPO40703 Verongula cf. rigida Esper Strain Aplysinidae Eukaryota n.a. n.a. n.a. PMID[32040314]
NPO25355 Dactylospongia elegans Species Thorectidae Eukaryota n.a. n.a. n.a. PMID[7964793]
NPO25355 Dactylospongia elegans Species Thorectidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO40703 Verongula cf. rigida Esper Strain Aplysinidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25355 Dactylospongia elegans Species Thorectidae 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
NPT306 Cell line PC-3 Homo sapiens IC50 > 10000.0 nM PMID[32040314]
NPT165 Cell line HeLa Homo sapiens IC50 > 10000.0 nM PMID[32040314]
NPT83 Cell line MCF7 Homo sapiens IC50 > 10000.0 nM PMID[32040314]
NPT20972 Cell line SU.86.86 Homo sapiens Activity > 30.0 % PMID[31980363]
NPT20972 Cell line SU.86.86 Homo sapiens Activity > 20.0 % PMID[31980363]

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 LD50 = 4.0 mg/L PMID[10785412]

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 NPC241512 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 NPC6185
1.0 High Similarity NPC603829
0.8545 High Similarity NPC610435
0.7966 Intermediate Similarity NPC606374
0.7241 Intermediate Similarity NPC263997
0.7241 Intermediate Similarity NPC8518
0.6825 Remote Similarity NPC487226
0.6667 Remote Similarity NPC606327
0.6393 Remote Similarity NPC260139
0.6393 Remote Similarity NPC10001
0.629 Remote Similarity NPC481276
0.629 Remote Similarity NPC481275
0.629 Remote Similarity NPC601986
0.619 Remote Similarity NPC489707
0.6094 Remote Similarity NPC475823
0.6094 Remote Similarity NPC607841
0.6 Remote Similarity NPC36626
0.6 Remote Similarity NPC602082
0.5821 Remote Similarity NPC602428
0.5775 Remote Similarity NPC606951
0.5738 Remote Similarity NPC601807
0.5738 Remote Similarity NPC604631
0.5714 Remote Similarity NPC603676
0.5571 Remote Similarity NPC185929
0.5469 Remote Similarity NPC99308
0.5342 Remote Similarity NPC24596
0.5303 Remote Similarity NPC603097
0.5263 Remote Similarity NPC149822
0.5263 Remote Similarity NPC608629
0.5091 Remote Similarity NPC146910

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC241512 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