Natural Product: NPC247783

Natural Product IDNPC247783
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 12Rhydroxylabda-8(17),13(16),14-Trien-19-Oic Acid
IUPAC Name (1S,4aR,5S,8aR)-5-[(2R)-2-hydroxy-3-methylidenepent-4-enyl]-1,4a-dimethyl-6-methylidene-3,4,5,7,8,8a-hexahydro-2H-naphthalene-1-carboxylic acid
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2385631
PubChem CID 71725776
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 BJIYGXNZLPKDHO-PNDFQMOFSA-N
Standard InCHI InChI=1S/C20H30O3/c1-6-13(2)16(21)12-15-14(3)8-9-17-19(15,4)10-7-11-20(17,5)18(22)23/h6,15-17,21H,1-3,7-12H2,4-5H3,(H,22,23)/t15-,16+,17+,19+,20-/m0/s1
SMILES C=CC(=C)[C@@H](C[C@H]1C(=C)CC[C@@H]2[C@]1(C)CCC[C@]2(C)C(=O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   318.22 Volume:   353.188
?
Van der Waals volume.
Dense:   0.901 LogP:   3.15
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.767
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.1
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   15.0
TPSA:   57.53
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.585 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.609 Fsp3:   0.65
MCE-18:   45.818
?
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:   0.446 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.012
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.002
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.833 Promiscuous compounds:   0.154

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.871 MDCK Permeability:   -4.782
Pgp-inhibitor:   0.011 Pgp-substrate:   0.001
PAMPA:   0.924
?
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%):   0.122 30% Bioavailability (F30%):   0.054
50% Bioavailability (F50%):   0.536

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.889
Plasma Protein Binding (PPB):   96.727% Volume Distribution (VD):   -0.456
Fu: 2.41%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.993 BCRP inhibitor:   0.008
BSEP inhibitor:   0.81

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.41 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.098 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.062
HLM stability:   0.035
?
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):  3.334 Half-life (T1/2):  1.465

ADMET: Toxicity

hERG Blockers:  0.029 hERG Blockers (10um):  0.207
Human Hepatotoxicity (H-HT):  0.602 Drug-induced Liver Injury (DILI):  0.605
AMES Toxicity:  0.351 Rat Oral Acute Toxicity:  0.838
Maximum Recommended Daily Dose:  0.645 Skin Sensitization:  0.997
Carcinogencity:  0.779 Eye Corrosion:  0.878
Eye Irritation:  0.954 Respiratory Toxicity:  0.945
Drug-induced Neurotoxicity:  0.776 Ototoxicity:  0.441
Hematotoxicity:  0.225 Drug-induced Nephrotoxicity:  0.87
Genotoxicity:  0.777 RPMI-8226 Immunitoxicity:  0.052
A549 Cytotoxicity:  0.192 Hek293 Cytotoxicity:  0.242
BCF:   0.777
?
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:   3.664
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.249
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.528
?
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
NPO32847 fokienia hodginsii Species Cupressaceae Eukaryota Twigs and Leaves n.a. n.a. PMID[23691952]

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
NPT660 Cell line SW480 Homo sapiens IC50 > 40000.0 nM PMID[21955940]
NPT83 Cell line MCF7 Homo sapiens IC50 > 40000.0 nM PMID[15620246]
NPT81 Cell line A549 Homo sapiens IC50 > 40000.0 nM PubChem BioAssay data set
NPT659 Cell line SMMC-7721 Homo sapiens IC50 > 40000.0 nM PMID[21761866]
NPT116 Cell line HL-60 Homo sapiens IC50 > 40000.0 nM DrugMatrix in vitro pharmacology data

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 NPC247783 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 NPC269543
0.6852 Remote Similarity NPC18819
0.6852 Remote Similarity NPC46610
0.6792 Remote Similarity NPC237591
0.6792 Remote Similarity NPC3753
0.6727 Remote Similarity NPC239098
0.6604 Remote Similarity NPC481630
0.6545 Remote Similarity NPC91369
0.6481 Remote Similarity NPC198240
0.6379 Remote Similarity NPC232344
0.6364 Remote Similarity NPC59436
0.6296 Remote Similarity NPC488498
0.6296 Remote Similarity NPC61952
0.6296 Remote Similarity NPC603184
0.625 Remote Similarity NPC471159
0.625 Remote Similarity NPC123880
0.6182 Remote Similarity NPC72343
0.6182 Remote Similarity NPC36616
0.6167 Remote Similarity NPC477782
0.6066 Remote Similarity NPC477783
0.5932 Remote Similarity NPC40228
0.5833 Remote Similarity NPC600691
0.5714 Remote Similarity NPC99154
0.5645 Remote Similarity NPC14203
0.5645 Remote Similarity NPC229584
0.5614 Remote Similarity NPC161923
0.5614 Remote Similarity NPC183503
0.5614 Remote Similarity NPC283908
0.5614 Remote Similarity NPC103958
0.5614 Remote Similarity NPC610917
0.55 Remote Similarity NPC479385
0.5345 Remote Similarity NPC170985
0.5333 Remote Similarity NPC82979
0.5333 Remote Similarity NPC312480
0.5254 Remote Similarity NPC165711
0.5254 Remote Similarity NPC109854
0.5254 Remote Similarity NPC601236
0.5254 Remote Similarity NPC606906
0.5246 Remote Similarity NPC470958
0.5167 Remote Similarity NPC73882
0.5156 Remote Similarity NPC479671
0.5152 Remote Similarity NPC46536
0.5152 Remote Similarity NPC138139
0.5152 Remote Similarity NPC603180
0.5147 Remote Similarity NPC610335
0.5082 Remote Similarity NPC610334

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC247783 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