Natural Product: NPC103958

Natural Product IDNPC103958
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,7R,10As)-7-Ethenyl-1,4A,7-Trimethyl-3,4,4B,5,6,9,10,10A-Octahydro-2H-Phenanthrene-1-Carboxylic Acid
IUPAC Name (1R,4aS,4bR,7R,10aS)-7-ethenyl-1,4a,7-trimethyl-3,4,4b,5,6,9,10,10a-octahydro-2H-phenanthrene-1-carboxylic acid
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1735595
PubChem CID 10086296
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 MHVJRKBZMUDEEV-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/h5,13,15-16H,1,6-12H2,2-4H3,(H,21,22)/t15-,16+,18+,19+,20-/m1/s1
SMILES C=C[C@@]1(C)CC[C@@H]2C(=C1)CC[C@H]1[C@@]2(C)CCC[C@@]1(C)C(=O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   302.22 Volume:   338.478
?
Van der Waals volume.
Dense:   0.893 LogP:   3.402
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.868
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.782
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The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
TPSA:   37.3
?
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:   4.381 Fsp3:   0.75
MCE-18:   59.086
?
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:   0.576 Fluc inhibitor:   0.002
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.004
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.005
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.92 Promiscuous compounds:   0.087

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.313 MDCK Permeability:   -4.965
Pgp-inhibitor:   0.728 Pgp-substrate:   0.001
PAMPA:   0.643
?
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%):   0.127 30% Bioavailability (F30%):   0.069
50% Bioavailability (F50%):   0.481

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.942
Plasma Protein Binding (PPB):   97.489% Volume Distribution (VD):   -0.18
Fu: 2.288%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.963 BCRP inhibitor:   0.091
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   0.023 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.282 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.983 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.003
CYP3A4-inhibitor:   0.548 CYP3A4-substrate:   0.039
CYP2B6-substrate:   0.002 CYP2C8-inhibitor:   0.612
HLM stability:   0.01
?
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):  2.522 Half-life (T1/2):  0.968

ADMET: Toxicity

hERG Blockers:  0.02 hERG Blockers (10um):  0.044
Human Hepatotoxicity (H-HT):  0.499 Drug-induced Liver Injury (DILI):  0.541
AMES Toxicity:  0.228 Rat Oral Acute Toxicity:  0.208
Maximum Recommended Daily Dose:  0.201 Skin Sensitization:  0.957
Carcinogencity:  0.834 Eye Corrosion:  0.995
Eye Irritation:  0.996 Respiratory Toxicity:  0.884
Drug-induced Neurotoxicity:  0.027 Ototoxicity:  0.242
Hematotoxicity:  0.443 Drug-induced Nephrotoxicity:  0.788
Genotoxicity:  0.385 RPMI-8226 Immunitoxicity:  0.022
A549 Cytotoxicity:  0.028 Hek293 Cytotoxicity:  0.056
BCF:   1.765
?
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:   4.277
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.624
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.131
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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
NPO6570 Cinnamomum philippinense Species Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3179 Eria bicolor Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25173 Phebalium squamulosum Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2233 Salvia dugesii Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3179 Eria bicolor Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2233 Salvia dugesii Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6570 Cinnamomum philippinense Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25173 Phebalium squamulosum Species Rutaceae 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
NPT154 Individual protein Mothers against decapentaplegic homolog 3 Homo sapiens Potency n.a. 25118.9 nM PubChem BioAssay data set
NPT11 Individual protein Guanine nucleotide-binding protein G(s), subunit alpha Homo sapiens Potency n.a. 50118.7 nM PubChem BioAssay data set
NPT161 Individual protein Rap guanine nucleotide exchange factor 4 Homo sapiens Potency n.a. 44668.4 nM PubChem BioAssay data set
NPT831 Individual protein Serine/threonine-protein kinase PLK1 Homo sapiens Potency n.a. 29934.9 nM PubChem BioAssay data set
NPT861 Individual protein Isocitrate dehydrogenase [NADP] cytoplasmic Homo sapiens Potency n.a. 50118.7 nM PubChem BioAssay data set
NPT755 Individual protein Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 Homo sapiens Potency n.a. 89125.1 nM PubChem BioAssay data set
NPT64 Individual protein ATPase family AAA domain-containing protein 5 Homo sapiens Potency n.a. 14575.0 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT65 Cell line HepG2 Homo sapiens Potency n.a. 35481.3 nM PubChem BioAssay data set
NPT177 Tissue Aorta Rattus norvegicus Inhibition = 73.2 % PMID[23916147]
NPT2 Others Unspecified n.a. Potency n.a. 16360.1 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 11220.2 nM PubChem BioAssay data set

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 NPC103958 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 NPC161923
1.0 High Similarity NPC183503
1.0 High Similarity NPC283908
1.0 High Similarity NPC610917
0.7115 Intermediate Similarity NPC610334
0.661 Remote Similarity NPC606907
0.6604 Remote Similarity NPC302661
0.6415 Remote Similarity NPC165711
0.6111 Remote Similarity NPC192540
0.6111 Remote Similarity NPC109854
0.5926 Remote Similarity NPC198240
0.5926 Remote Similarity NPC237591
0.5926 Remote Similarity NPC3753
0.5873 Remote Similarity NPC610335
0.5818 Remote Similarity NPC59436
0.5741 Remote Similarity NPC488498
0.5741 Remote Similarity NPC61952
0.5741 Remote Similarity NPC481630
0.5741 Remote Similarity NPC603184
0.5714 Remote Similarity NPC471159
0.5714 Remote Similarity NPC123880
0.5714 Remote Similarity NPC18819
0.5714 Remote Similarity NPC46610
0.5636 Remote Similarity NPC72343
0.5636 Remote Similarity NPC36616
0.5614 Remote Similarity NPC269543
0.5614 Remote Similarity NPC247783
0.5614 Remote Similarity NPC239098
0.5472 Remote Similarity NPC601231
0.5472 Remote Similarity NPC607405
0.5455 Remote Similarity NPC99154
0.5439 Remote Similarity NPC91369
0.5424 Remote Similarity NPC40228
0.541 Remote Similarity NPC479671
0.5345 Remote Similarity NPC82979
0.5333 Remote Similarity NPC232344
0.5333 Remote Similarity NPC600691
0.5161 Remote Similarity NPC14203
0.5161 Remote Similarity NPC229584
0.5161 Remote Similarity NPC477782
0.5098 Remote Similarity NPC170070
0.5079 Remote Similarity NPC477783

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC103958 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