Natural Product: NPC192540

Natural Product IDNPC192540
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (1R,4As,4Br,7S,10As)-7-Ethenyl-1,4A,7-Trimethyl-3,4,4B,5,6,8,10,10A-Octahydro-2H-Phenanthrene-1-Carboxylic Acid
IUPAC Name (1R,4aS,4bR,7S,10aS)-7-ethenyl-1,4a,7-trimethyl-3,4,4b,5,6,8,10,10a-octahydro-2H-phenanthrene-1-carboxylic acid
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2420225
PubChem CID 73349191
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001551] Diterpenoids

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 MXYATHGRPJZBNA-XIHRTOKZSA-N
Standard InCHI InChI=1S/C20H30O2/c1-5-18(2)12-9-15-14(13-18)7-8-16-19(15,3)10-6-11-20(16,4)17(21)22/h5,7,15-16H,1,6,8-13H2,2-4H3,(H,21,22)/t15-,16+,18+,19+,20-/m1/s1
SMILES C=C[C@@]1(C)CC[C@@H]2C(=CC[C@H]3[C@@]2(C)CCC[C@@]3(C)C(=O)O)C1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   302.22 Volume:   338.478
?
Van der Waals volume.
Dense:   0.893 LogP:   3.475
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.85
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.582
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The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
TPSA:   37.3
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Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.711 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.448 Fsp3:   0.75
MCE-18:   59.086
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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:   0.554 Fluc inhibitor:   0.039
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.005
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.001
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.912 Promiscuous compounds:   0.035

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.176 MDCK Permeability:   -4.937
Pgp-inhibitor:   0.021 Pgp-substrate:   0.002
PAMPA:   0.989
?
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%):   0.032 30% Bioavailability (F30%):   0.028
50% Bioavailability (F50%):   0.691

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.872
Plasma Protein Binding (PPB):   97.13% Volume Distribution (VD):   -0.604
Fu: 2.528%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.766 BCRP inhibitor:   0.315
BSEP inhibitor:   0.964

ADMET: Metabolism

CYP1A2-inhibitor:   0.12 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.537 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.711 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.003
CYP3A4-inhibitor:   0.86 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.003 CYP2C8-inhibitor:   0.049
HLM stability:   0.005
?
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):  2.633 Half-life (T1/2):  0.746

ADMET: Toxicity

hERG Blockers:  0.005 hERG Blockers (10um):  0.028
Human Hepatotoxicity (H-HT):  0.424 Drug-induced Liver Injury (DILI):  0.217
AMES Toxicity:  0.113 Rat Oral Acute Toxicity:  0.21
Maximum Recommended Daily Dose:  0.21 Skin Sensitization:  0.973
Carcinogencity:  0.77 Eye Corrosion:  0.997
Eye Irritation:  0.995 Respiratory Toxicity:  0.879
Drug-induced Neurotoxicity:  0.01 Ototoxicity:  0.211
Hematotoxicity:  0.413 Drug-induced Nephrotoxicity:  0.714
Genotoxicity:  0.158 RPMI-8226 Immunitoxicity:  0.018
A549 Cytotoxicity:  0.077 Hek293 Cytotoxicity:  0.054
BCF:   1.73
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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:   4.306
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.681
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.16
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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
NPO26558 Physocarpus capitatus Species Rosaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9277 Ammothamnus songoricus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26779 Helianthus strumosus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO26779 Helianthus strumosus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO26706 Dictyota pardalis Species Dictyotaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12676 Berberis mingetsensis Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26558 Physocarpus capitatus Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26852 Cryptocarya konishii Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26114 Dorstenia convexa Species Moraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9277 Ammothamnus songoricus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10843 Melanelixia subglabra Species Parmeliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4202 Kopsia terengganensis Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26779 Helianthus strumosus Species Asteraceae 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
NPT177 Tissue Aorta Rattus norvegicus Inhibition = 50.8 % PMID[23916147]

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 NPC192540 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
0.7059 Intermediate Similarity NPC279666
0.6364 Remote Similarity NPC82979
0.6111 Remote Similarity NPC161923
0.6111 Remote Similarity NPC183503
0.6111 Remote Similarity NPC283908
0.6111 Remote Similarity NPC103958
0.6111 Remote Similarity NPC610917
0.6038 Remote Similarity NPC480561
0.5926 Remote Similarity NPC484817
0.5536 Remote Similarity NPC237591
0.5536 Remote Similarity NPC3753
0.5439 Remote Similarity NPC59436
0.5439 Remote Similarity NPC109854
0.5424 Remote Similarity NPC483605
0.537 Remote Similarity NPC601231
0.537 Remote Similarity NPC607405
0.5345 Remote Similarity NPC302661
0.5263 Remote Similarity NPC198240
0.5254 Remote Similarity NPC610334
0.5172 Remote Similarity NPC165711
0.5088 Remote Similarity NPC610518

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC192540 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