Natural Product: NPC148189

Natural Product IDNPC148189
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 DMHADBQKVWXPPM-HPKGDXISSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 6430770
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001551] Diterpenoids
          • [CHEMONTID:0000008] Cembrane 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 DMHADBQKVWXPPM-HPKGDXISSA-N
Standard InCHI InChI=1S/C20H32/c1-16(2)20-14-12-18(4)10-6-8-17(3)9-7-11-19(5)13-15-20/h8,10-12,14,16,20H,6-7,9,13,15H2,1-5H3/b14-12+,17-8+,18-10-,19-11+
SMILES CC(C)C1/C=C/C(=CC/C=C(C)/CC/C=C(C)/CC1)/C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   272.25 Volume:   335.374
?
Van der Waals volume.
Dense:   0.812 LogP:   5.521
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.926
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.637
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   14.0
TPSA:   0.0
?
Topological Polar Surface Area.
 H-Bond Acceptor:   0.0
H-Bond Donor:   0.0 Rings:   1.0
Heavy Atoms:   0.0

MedChem Properties

QED Drug-Likeness Score:   0.471 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.09 Fsp3:   0.6
MCE-18:   19.0
?
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:   0.948 Fluc inhibitor:   0.323
?
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:   0.008
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.989 Promiscuous compounds:   0.001

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.785 MDCK Permeability:   -4.698
Pgp-inhibitor:   0.99 Pgp-substrate:   0.004
PAMPA:   0.003
?
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):   0.001
20% Bioavailability (F20%):   0.004 30% Bioavailability (F30%):   0.024
50% Bioavailability (F50%):   0.315

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.027 MRP1:   0.927
Plasma Protein Binding (PPB):   97.719% Volume Distribution (VD):   0.308
Fu: 2.58%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.994
OATP1B3 inhibitor:   0.931 BCRP inhibitor:   0.004
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   0.005 CYP1A2-substrate:   0.993
CYP2C19-inhibitor:   0.951 CYP2C19-substrate:   0.363
CYP2C9-inhibitor:   0.892 CYP2C9-substrate:   0.027
CYP2D6-inhibitor:   0.966 CYP2D6-substrate:   0.212
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.999
CYP2B6-substrate:   0.368 CYP2C8-inhibitor:   1.0
HLM stability:   0.928
?
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):  10.713 Half-life (T1/2):  0.482

ADMET: Toxicity

hERG Blockers:  0.083 hERG Blockers (10um):  0.133
Human Hepatotoxicity (H-HT):  0.842 Drug-induced Liver Injury (DILI):  0.679
AMES Toxicity:  0.048 Rat Oral Acute Toxicity:  0.012
Maximum Recommended Daily Dose:  0.354 Skin Sensitization:  0.996
Carcinogencity:  0.059 Eye Corrosion:  0.595
Eye Irritation:  0.991 Respiratory Toxicity:  0.241
Drug-induced Neurotoxicity:  0.723 Ototoxicity:  0.105
Hematotoxicity:  0.093 Drug-induced Nephrotoxicity:  0.336
Genotoxicity:  0.01 RPMI-8226 Immunitoxicity:  0.147
A549 Cytotoxicity:  0.316 Hek293 Cytotoxicity:  0.451
BCF:   3.496
?
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:   4.708
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.537
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.915
?
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
NPO15315 Boswellia carterii Species Burseraceae Eukaryota n.a. n.a. n.a. PMID[24195447]
NPO15315 Boswellia carterii Species Burseraceae Eukaryota Gum resin n.a. n.a. PMID[26457560]
NPO18735 Pinus mugo Species Pinaceae Eukaryota n.a. n.a. n.a. PMID[31475763]
NPO11882 Cedrus libani Species Pinaceae Eukaryota n.a. n.a. n.a. PMID[32092041]
NPO45866 Taiwania flousiana Species Cupressaceae Eukaryota n.a. n.a. n.a. PMID[32093424]
NPO14774 Cymbopogon schoenanthus Species Poaceae Eukaryota n.a. n.a. n.a. PMID[32286731]
NPO23183 Pinus halepensis Species Pinaceae Eukaryota n.a. n.a. n.a. PMID[34847783]
NPO14774 Cymbopogon schoenanthus Species Poaceae Eukaryota n.a. n.a. n.a. PMID[34946632]
NPO58153 Ochradenus arabicus Species Resedaceae Eukaryota n.a. n.a. n.a. PMID[36616238]
NPO63446 Picea engelmannii subsp. engelmannii Genus Pinaceae Eukaryota n.a. n.a. n.a. PMID[36985451]
NPO54547 Pseudotsuga menziesii var. glauca Species Pinaceae Eukaryota n.a. n.a. n.a. PMID[36985451]
NPO23183 Pinus halepensis Species Pinaceae Eukaryota n.a. n.a. n.a. PMID[38202742]
NPO18680 Larix decidua Species Pinaceae Eukaryota n.a. n.a. n.a. PMID[38259911]
NPO11541 Curcuma xanthorrhiza Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[39409552]
NPO42856 Salvia Sahendica Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[39438657]
NPO14774 Cymbopogon schoenanthus Species Poaceae Eukaryota n.a. n.a. n.a. PMID[39545686]
NPO11541 Curcuma xanthorrhiza Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23183 Pinus halepensis Species Pinaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18735 Pinus mugo Species Pinaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11882 Cedrus libani Species Pinaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15315 Boswellia carterii Species Burseraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18680 Larix decidua Species Pinaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14774 Cymbopogon schoenanthus Species Poaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11541 Curcuma xanthorrhiza Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15315 Boswellia carterii Species Burseraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15315 Boswellia carterii Species Burseraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11541 Curcuma xanthorrhiza Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15315 Boswellia carterii Species Burseraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO15315 Boswellia carterii Species Burseraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO14774 Cymbopogon schoenanthus Species Poaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15315 Boswellia carterii Species Burseraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18680 Larix decidua Species Pinaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23183 Pinus halepensis Species Pinaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11882 Cedrus libani Species Pinaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11541 Curcuma xanthorrhiza Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18735 Pinus mugo Species Pinaceae 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
NPO11541 Curcuma xanthorrhiza Oil n.a. 0.42 n.a. n.a. % PMID[39409552]
NPO11541 Curcuma xanthorrhiza Oil n.a. 0.64 n.a. n.a. % PMID[39409552]
NPO11541 Curcuma xanthorrhiza Oil n.a. 0.67 n.a. n.a. % PMID[39409552]
NPO11541 Curcuma xanthorrhiza Oil n.a. 0.80 n.a. n.a. % PMID[39409552]
NPO11882 Cedrus libani Oil n.a. 0.1±0.1 n.a. n.a. % PMID[32092041]
NPO14774 Cymbopogon schoenanthus Oil n.a. 0.81 n.a. n.a. % PMID[39545686]
NPO18680 Larix decidua Oil n.a. 0.18 ± 0.03 n.a. n.a. % PMID[38259911]
NPO18680 Larix decidua Oil n.a. 0.07 ± 0.00 n.a. n.a. % PMID[38259911]
NPO18680 Larix decidua Oil n.a. 0.16 ± 0.07 n.a. n.a. % PMID[38259911]
NPO18735 Pinus mugo Oil n.a. 0.2 n.a. n.a. % PMID[31475763]
NPO18735 Pinus mugo Oil n.a. 0.1 n.a. n.a. % PMID[31475763]
NPO23183 Pinus halepensis Oil n.a. 2.45 n.a. n.a. % PMID[34847783]
NPO23183 Pinus halepensis Oil n.a. 2.25 n.a. n.a. % PMID[34847783]
NPO23183 Pinus halepensis Oil n.a. 2.19 n.a. n.a. % PMID[34847783]
NPO23183 Pinus halepensis Oil n.a. 8.05 n.a. n.a. % PMID[34847783]
NPO23183 Pinus halepensis Oil n.a. 0.99 n.a. n.a. % PMID[34847783]
NPO23183 Pinus halepensis Oil n.a. 3.73 n.a. n.a. % PMID[34847783]
NPO23183 Pinus halepensis Oil n.a. 7.27 n.a. n.a. % PMID[34847783]
NPO23183 Pinus halepensis Oil n.a. 1.91 n.a. n.a. % PMID[34847783]
NPO23183 Pinus halepensis Oil n.a. 6.18 n.a. n.a. % PMID[34847783]
NPO23183 Pinus halepensis Oil n.a. 8.51 n.a. n.a. % PMID[34847783]
NPO42856 Salvia Sahendica Oil Stems 0.1 n.a. n.a. % PMID[39438657]
NPO45866 Taiwania flousiana Oil n.a. 0.16 n.a. n.a. % PMID[32093424]
NPO54547 Pseudotsuga menziesii var. glauca Oil Leaves 0.1 n.a. n.a. % PMID[36985451]
NPO54547 Pseudotsuga menziesii var. glauca Oil Leaves 0.2 n.a. n.a. % PMID[36985451]
NPO58153 Ochradenus arabicus Oil n.a. 0.00 n.a. n.a. % PMID[36616238]
NPO58153 Ochradenus arabicus Oil n.a. 0.33 ± 0.02 n.a. n.a. % PMID[36616238]
NPO63446 Picea engelmannii subsp. engelmannii Oil Leaves 0.6 n.a. n.a. % PMID[36985451]

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

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 NPC148189 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
0.6286 Remote Similarity NPC218918
0.6286 Remote Similarity NPC120926

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC148189 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