Natural Product: NPC42657

Natural Product IDNPC42657
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Podocaric Acid
IUPAC Name (1S,4aS,10aR)-6-hydroxy-1,4a-dimethyl-2,3,4,9,10,10a-hexahydrophenanthrene-1-carboxylic acid
Synonyms Podocaric Acid; Podocarpic Acid
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL421115
PubChem CID 93017
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 VJILEYKNALCDDV-OIISXLGYSA-N
Standard InCHI InChI=1S/C17H22O3/c1-16-8-3-9-17(2,15(19)20)14(16)7-5-11-4-6-12(18)10-13(11)16/h4,6,10,14,18H,3,5,7-9H2,1-2H3,(H,19,20)/t14-,16-,17+/m1/s1
SMILES Oc1ccc2c(c1)[C@@]1(C)CCC[C@]([C@@H]1CC2)(C)C(=O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   274.16 Volume:   292.744
?
Van der Waals volume.
Dense:   0.937 LogP:   2.448
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.42
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.357
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The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 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:   0.824 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.457 Fsp3:   0.588
MCE-18:   71.852
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.075 Fluc inhibitor:   0.022
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.06
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.02
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.449 Promiscuous compounds:   0.035

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.722 MDCK Permeability:   -4.865
Pgp-inhibitor:   0.0 Pgp-substrate:   0.248
PAMPA:   0.915
?
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%):   0.737 30% Bioavailability (F30%):   0.779
50% Bioavailability (F50%):   0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.575 MRP1:   0.959
Plasma Protein Binding (PPB):   95.309% Volume Distribution (VD):   -0.527
Fu: 2.943%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.997
OATP1B3 inhibitor:   0.993 BCRP inhibitor:   0.048
BSEP inhibitor:   0.418

ADMET: Metabolism

CYP1A2-inhibitor:   0.062 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.952 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.048 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.957 CYP3A4-substrate:   0.47
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.001
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):  3.626 Half-life (T1/2):  1.391

ADMET: Toxicity

hERG Blockers:  0.122 hERG Blockers (10um):  0.247
Human Hepatotoxicity (H-HT):  0.66 Drug-induced Liver Injury (DILI):  0.322
AMES Toxicity:  0.255 Rat Oral Acute Toxicity:  0.312
Maximum Recommended Daily Dose:  0.571 Skin Sensitization:  0.922
Carcinogencity:  0.748 Eye Corrosion:  0.203
Eye Irritation:  0.977 Respiratory Toxicity:  0.885
Drug-induced Neurotoxicity:  0.183 Ototoxicity:  0.359
Hematotoxicity:  0.248 Drug-induced Nephrotoxicity:  0.383
Genotoxicity:  0.388 RPMI-8226 Immunitoxicity:  0.022
A549 Cytotoxicity:  0.067 Hek293 Cytotoxicity:  0.278
BCF:   0.775
?
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:   3.687
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.998
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.397
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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
NPO3352 Dianthus barbatus Species Caryophyllaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28038 Banisteriopsis argentea Species Malpighiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3352 Dianthus barbatus Species Caryophyllaceae 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
NPT1794 Individual protein LXR-alpha Homo sapiens IC50 > 50000.0 nM PMID[15911262]
NPT1746 Individual protein LXR-beta Homo sapiens IC50 > 50000.0 nM PMID[15911262]
NPT1794 Individual protein LXR-alpha Homo sapiens EC50 > 50000.0 nM PMID[16124770]
NPT1746 Individual protein LXR-beta Homo sapiens EC50 > 50000.0 nM PMID[16124770]
NPT2552 Individual protein Calcium-activated potassium channel subunit alpha-1 Homo sapiens Activity = 206.9 % PMID[18789683]
NPT698 Individual protein Regulator of G-protein signaling 4 Homo sapiens Potency n.a. 1062.1 nM PubChem BioAssay data set
NPT67 Individual protein Cholinesterase Equus caballus Inhibition = -2.99 % PMID[23062825]
NPT66 Individual protein Acetylcholinesterase Electrophorus electricus Inhibition = -4.47 % PMID[23062825]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT616 Cell line MDCK Canis lupus familiaris CC50 = 91200.0 nM PMID[25815159]
NPT28797 Organism Cryptococcus neoformans Cryptococcus neoformans MIC > 117000.0 nM PMID[35477062]
NPT20 Organism Candida albicans Candida albicans MIC > 117000.0 nM PMID[35477062]
NPT173 Organism Klebsiella pneumoniae Klebsiella pneumoniae MIC > 117000.0 nM PMID[35477062]
NPT1453 Organism Influenza A virus (A/PR/8/34(H1N1)) Influenza A virus (A/Puerto Rico/8/1934(H1N1)) EC50 = 18200.0 nM PMID[25815159]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC > 117000.0 nM PMID[35477062]
NPT19 Organism Escherichia coli Escherichia coli MIC > 117000.0 nM PMID[35477062]
NPT18 Organism Pseudomonas aeruginosa Pseudomonas aeruginosa MIC > 117000.0 nM PMID[35477062]
NPT742 Organism Influenza A virus Influenza A virus Activity < 50.0 % PMID[25815159]
NPT22036 Cell line HL Homo sapiens Activity = 27.9 % PMID[29043803]
NPT747 Organism Acinetobacter baumannii Acinetobacter baumannii MIC > 117000.0 nM PMID[35477062]

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 NPC42657 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
0.6727 Remote Similarity NPC162935
0.6727 Remote Similarity NPC249340
0.6491 Remote Similarity NPC603947
0.6429 Remote Similarity NPC95126
0.6379 Remote Similarity NPC94751
0.6379 Remote Similarity NPC142326
0.6364 Remote Similarity NPC128248
0.6364 Remote Similarity NPC136810
0.625 Remote Similarity NPC133809
0.6207 Remote Similarity NPC212891
0.6129 Remote Similarity NPC480865
0.5932 Remote Similarity NPC221275
0.5738 Remote Similarity NPC45794
0.5667 Remote Similarity NPC608624
0.5161 Remote Similarity NPC480861
0.5079 Remote Similarity NPC480862
0.5079 Remote Similarity NPC480860

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC42657 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
0.5763 Remote Similarity NPD4199 Phase 3

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