Natural Product: NPC234337

Natural Product IDNPC234337
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 7Beta-Hydroxydehydroabietic Acid
IUPAC Name (1R,4aS,9S,10aR)-9-hydroxy-1,4a-dimethyl-7-propan-2-yl-2,3,4,9,10,10a-hexahydrophenanthrene-1-carboxylic acid
Synonyms 7Beta-Hydroxydehydroabietic Acid
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL604787
PubChem CID 13370052
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 GPFVBJYXFRIOFB-ONCXSQPRSA-N
Standard InCHI InChI=1S/C20H28O3/c1-12(2)13-6-7-15-14(10-13)16(21)11-17-19(15,3)8-5-9-20(17,4)18(22)23/h6-7,10,12,16-17,21H,5,8-9,11H2,1-4H3,(H,22,23)/t16-,17+,19+,20+/m0/s1
SMILES CC(C)c1ccc2c(c1)[C@H](C[C@@H]1[C@]2(C)CCC[C@@]1(C)C(=O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   316.2 Volume:   344.632
?
Van der Waals volume.
Dense:   0.918 LogP:   3.344
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.841
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.792
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   17.0
TPSA:   57.53
?
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:   0.85 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.837 Fsp3:   0.65
MCE-18:   76.667
?
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:   0.304 Fluc inhibitor:   0.004
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.016
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.006
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.213 Promiscuous compounds:   0.007

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.906 MDCK Permeability:   -4.902
Pgp-inhibitor:   0.118 Pgp-substrate:   0.025
PAMPA:   0.667
?
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):   0.004
20% Bioavailability (F20%):   0.207 30% Bioavailability (F30%):   0.223
50% Bioavailability (F50%):   0.896

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.996
Plasma Protein Binding (PPB):   97.828% Volume Distribution (VD):   -0.52
Fu: 2.609%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.996
OATP1B3 inhibitor:   0.987 BCRP inhibitor:   0.008
BSEP inhibitor:   0.988

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.003 CYP2C19-substrate:   0.069
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.999 CYP3A4-substrate:   0.035
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.304
HLM stability:   0.0
?
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):  3.342 Half-life (T1/2):  1.386

ADMET: Toxicity

hERG Blockers:  0.039 hERG Blockers (10um):  0.123
Human Hepatotoxicity (H-HT):  0.787 Drug-induced Liver Injury (DILI):  0.607
AMES Toxicity:  0.334 Rat Oral Acute Toxicity:  0.334
Maximum Recommended Daily Dose:  0.781 Skin Sensitization:  0.917
Carcinogencity:  0.81 Eye Corrosion:  0.18
Eye Irritation:  0.973 Respiratory Toxicity:  0.861
Drug-induced Neurotoxicity:  0.081 Ototoxicity:  0.78
Hematotoxicity:  0.401 Drug-induced Nephrotoxicity:  0.958
Genotoxicity:  0.15 RPMI-8226 Immunitoxicity:  0.021
A549 Cytotoxicity:  0.02 Hek293 Cytotoxicity:  0.119
BCF:   0.708
?
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:   3.525
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.045
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.36
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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
NPO2882 Abies georgei Species Pinaceae Eukaryota aerial parts Zhongdian city, Yunnan Province of China n.a. PMID[20022253]
NPO29383 Abies holophylla Species Pinaceae Eukaryota trunk n.a. n.a. PMID[24224862]
NPO29383 Abies holophylla Species Pinaceae Eukaryota Trunk n.a. n.a. PMID[26812172]
NPO29383 Abies holophylla Species Pinaceae Eukaryota n.a. n.a. n.a. PMID[30063340]
NPO12422 Pinus massoniana Species Pinaceae Eukaryota n.a. n.a. n.a. PMID[32100544]
NPO3762 Amentotaxus argotaenia Species Taxaceae Eukaryota Leaves; Twigs n.a. n.a. PMID[32633512]
NPO12422 Pinus massoniana Species Pinaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4144 Scutia buxifolia Species Rhamnaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11832 Pinus banksiana Species Pinaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1191 Castanea mollissima Species Fagaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29383 Abies holophylla Species Pinaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3102 Arachniodes exilis Species Dryopteridaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9522 Pericopsis angolensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9311 Parkia clappertoniana Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9051 Delesseria sanguinea Species Delesseriaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2882 Abies georgei Species Pinaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO822 Cressa cretica Species Convolvulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12422 Pinus massoniana Species Pinaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO4144 Scutia buxifolia Species Rhamnaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO1191 Castanea mollissima Species Fagaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12322 Amomum krervanh Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO1191 Castanea mollissima Species Fagaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO9522 Pericopsis angolensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12422 Pinus massoniana Species Pinaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO4144 Scutia buxifolia Species Rhamnaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3102 Arachniodes exilis Species Dryopteridaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12422 Pinus massoniana Species Pinaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO1191 Castanea mollissima Species Fagaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO12322 Amomum krervanh Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO12422 Pinus massoniana Species Pinaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO1191 Castanea mollissima Species Fagaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12895 Polypodiodes niponica Species Polypodiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10177 Eria linearifolia Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11832 Pinus banksiana Species Pinaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29383 Abies holophylla Species Pinaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9522 Pericopsis angolensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9051 Delesseria sanguinea Species Delesseriaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10588 Diploschistes violarius Species Graphidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4144 Scutia buxifolia Species Rhamnaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9311 Parkia clappertoniana Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5205 Gymnoascus reesii Species Gymnoascaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12322 Amomum krervanh Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3762 Amentotaxus argotaenia Species Taxaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO822 Cressa cretica Species Convolvulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3102 Arachniodes exilis Species Dryopteridaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12422 Pinus massoniana 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

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
NPT113 Cell line RAW264.7 Mus musculus IC50 > 100.0 ug.mL-1 PMID[20022253]
NPT114 Cell line LoVo Homo sapiens IC50 > 25.0 ug.mL-1 PMID[20022253]
NPT76 Cell line C6 Rattus norvegicus Activity = 165.1 % PMID[26812172]
NPT76 Cell line C6 Rattus norvegicus Activity = 96.2 % PMID[26812172]
NPT81 Cell line A549 Homo sapiens IC50 > 10000.0 nM PMID[26812172]
NPT147 Cell line SK-MEL-2 Homo sapiens IC50 > 10000.0 nM PMID[26812172]
NPT34 Cell line BV-2 Mus musculus IC50 = 17900.0 nM PMID[27989668]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 25.0 ug.mL-1 PMID[20022253]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 10000.0 nM PMID[26812172]
NPT2 Others Unspecified n.a. IC50 > 100.0 ug.mL-1 PMID[20022253]

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 NPC234337 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 NPC133389
0.7636 Intermediate Similarity NPC183339
0.7241 Intermediate Similarity NPC253681
0.6316 Remote Similarity NPC128248
0.6316 Remote Similarity NPC136810
0.6102 Remote Similarity NPC93287
0.5806 Remote Similarity NPC94751
0.5806 Remote Similarity NPC142326
0.5645 Remote Similarity NPC480861
0.5574 Remote Similarity NPC293831
0.5574 Remote Similarity NPC369
0.5345 Remote Similarity NPC243601
0.5323 Remote Similarity NPC95126
0.5167 Remote Similarity NPC64642
0.5167 Remote Similarity NPC149455
0.5156 Remote Similarity NPC167323
0.5156 Remote Similarity NPC212891
0.5156 Remote Similarity NPC269923
0.5156 Remote Similarity NPC603947
0.5079 Remote Similarity NPC162935
0.5079 Remote Similarity NPC249340

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC234337 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