Natural Product: NPC165711

Natural Product IDNPC165711
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 8(14)-Podocarpen-13-On-18-Oic Acid
IUPAC Name (1R,4aR,4bS,10aR)-1,4a-dimethyl-7-oxo-3,4,4b,5,6,9,10,10a-octahydro-2H-phenanthrene-1-carboxylic acid
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2048510
PubChem CID 26183540
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0000025] Phenanthrenes and derivatives
        • [CHEMONTID:0000223] Hydrophenanthrenes

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 DXXGHDAWCPTRPU-XOSAIJSUSA-N
Standard InCHI InChI=1S/C17H24O3/c1-16-8-3-9-17(2,15(19)20)14(16)7-4-11-10-12(18)5-6-13(11)16/h10,13-14H,3-9H2,1-2H3,(H,19,20)/t13-,14+,16+,17+/m0/s1
SMILES O=C1CC[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:   276.17 Volume:   295.38
?
Van der Waals volume.
Dense:   0.935 LogP:   2.504
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.435
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.351
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   18.0
TPSA:   54.37
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.796 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.939 Fsp3:   0.765
MCE-18:   54.667
?
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:   0.157 Fluc inhibitor:   0.056
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.006
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.003
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.846 Promiscuous compounds:   0.131

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.863 MDCK Permeability:   -4.764
Pgp-inhibitor:   0.38 Pgp-substrate:   0.005
PAMPA:   0.885
?
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):   0.028
20% Bioavailability (F20%):   0.028 30% Bioavailability (F30%):   0.015
50% Bioavailability (F50%):   0.048

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.928
Plasma Protein Binding (PPB):   97.417% Volume Distribution (VD):   -0.349
Fu: 4.154%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   0.98 BCRP inhibitor:   0.005
BSEP inhibitor:   0.964

ADMET: Metabolism

CYP1A2-inhibitor:   0.03 CYP1A2-substrate:   0.001
CYP2C19-inhibitor:   0.213 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.003 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.999 CYP3A4-substrate:   0.061
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.331
HLM stability:   0.044
?
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):  2.864 Half-life (T1/2):  1.289

ADMET: Toxicity

hERG Blockers:  0.02 hERG Blockers (10um):  0.046
Human Hepatotoxicity (H-HT):  0.637 Drug-induced Liver Injury (DILI):  0.553
AMES Toxicity:  0.162 Rat Oral Acute Toxicity:  0.209
Maximum Recommended Daily Dose:  0.419 Skin Sensitization:  0.961
Carcinogencity:  0.662 Eye Corrosion:  0.716
Eye Irritation:  0.958 Respiratory Toxicity:  0.628
Drug-induced Neurotoxicity:  0.087 Ototoxicity:  0.353
Hematotoxicity:  0.542 Drug-induced Nephrotoxicity:  0.756
Genotoxicity:  0.702 RPMI-8226 Immunitoxicity:  0.031
A549 Cytotoxicity:  0.014 Hek293 Cytotoxicity:  0.04
BCF:   0.699
?
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:   3.427
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.944
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.262
?
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
NPO21014 Brucea antidysenterica Species Simaroubaceae Eukaryota n.a. n.a. n.a. PMID[2089121]
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]
NPO21014 Brucea antidysenterica Species Simaroubaceae Eukaryota n.a. n.a. n.a. PMID[3379416]
NPO21014 Brucea antidysenterica Species Simaroubaceae Eukaryota n.a. n.a. n.a. PMID[3443857]
NPO21014 Brucea antidysenterica Species Simaroubaceae Eukaryota n.a. n.a. n.a. PMID[3760882]
NPO21014 Brucea antidysenterica Species Simaroubaceae Eukaryota n.a. n.a. n.a. PMID[3841557]
NPO21014 Brucea antidysenterica Species Simaroubaceae Eukaryota n.a. n.a. n.a. PMID[7288443]
NPO21014 Brucea antidysenterica Species Simaroubaceae Eukaryota n.a. xylem n.a. PMID[8133299]
NPO21014 Brucea antidysenterica Species Simaroubaceae Eukaryota n.a. n.a. n.a. PMID[8133299]
NPO21014 Brucea antidysenterica Species Simaroubaceae Eukaryota n.a. n.a. n.a. PMID[8691212]
NPO22470 Corynebacterium glutamicum Species Corynebacteriaceae Bacteria n.a. n.a. n.a. Database[Article]
NPO19502 Squamopappus skutchii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22470 Corynebacterium glutamicum Species Corynebacteriaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO12422 Pinus massoniana Species Pinaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17292 Asparagus racemosus Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20619 Ougeinia dalbergioides n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO29383 Abies holophylla Species Pinaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12422 Pinus massoniana Species Pinaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21014 Brucea antidysenterica Species Simaroubaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12422 Pinus massoniana Species Pinaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21014 Brucea antidysenterica Species Simaroubaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12422 Pinus massoniana Species Pinaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO12422 Pinus massoniana Species Pinaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO21165 Phagnalon atlanticum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29383 Abies holophylla Species Pinaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22470 Corynebacterium glutamicum Species Corynebacteriaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO21014 Brucea antidysenterica Species Simaroubaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19502 Squamopappus skutchii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20619 Ougeinia dalbergioides n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO17292 Asparagus racemosus Species Asparagaceae 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
NPT568 Individual protein Matrix metalloproteinase-2 Homo sapiens IC50 = 33260.0 nM PMID[22658537]
NPT568 Individual protein Matrix metalloproteinase-2 Homo sapiens Inhibition > 30.0 % PMID[22658537]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT34 Cell line BV-2 Mus musculus IC50 = 18100.0 nM PMID[30063340]
NPT34 Cell line BV-2 Mus musculus Activity = 123.8 % PMID[30063340]
NPT783 Cell line MIA PaCa-2 Homo sapiens PC50 = 55.5 uM PMID[35395369]

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 NPC165711 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
0.6415 Remote Similarity NPC161923
0.6415 Remote Similarity NPC183503
0.6415 Remote Similarity NPC283908
0.6415 Remote Similarity NPC103958
0.6415 Remote Similarity NPC610917
0.6071 Remote Similarity NPC610334
0.6 Remote Similarity NPC109854
0.5714 Remote Similarity NPC59436
0.5636 Remote Similarity NPC99154
0.5636 Remote Similarity NPC481630
0.5614 Remote Similarity NPC471159
0.5614 Remote Similarity NPC123880
0.5574 Remote Similarity NPC479671
0.5536 Remote Similarity NPC198240
0.5536 Remote Similarity NPC237591
0.5536 Remote Similarity NPC72343
0.5536 Remote Similarity NPC3753
0.55 Remote Similarity NPC232344
0.5469 Remote Similarity NPC606907
0.5357 Remote Similarity NPC488498
0.5357 Remote Similarity NPC61952
0.5357 Remote Similarity NPC603184
0.5345 Remote Similarity NPC18819
0.5345 Remote Similarity NPC302661
0.5345 Remote Similarity NPC46610
0.5345 Remote Similarity NPC91369
0.5333 Remote Similarity NPC40228
0.5303 Remote Similarity NPC610335
0.5263 Remote Similarity NPC36616
0.5254 Remote Similarity NPC269543
0.5254 Remote Similarity NPC247783
0.5254 Remote Similarity NPC239098
0.5254 Remote Similarity NPC90055
0.5246 Remote Similarity NPC600691
0.5172 Remote Similarity NPC192540
0.5088 Remote Similarity NPC484817
0.5082 Remote Similarity NPC94163
0.5079 Remote Similarity NPC14203
0.5079 Remote Similarity NPC229584
0.5079 Remote Similarity NPC477782

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC165711 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