Natural Product: NPC484817

Natural Product IDNPC484817
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 ALNCCRQWKSHBLG-LNKGRISISA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
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 ALNCCRQWKSHBLG-LNKGRISISA-N
Standard InCHI InChI=1S/C20H28O3/c1-12(2)13-6-8-15-14(17(13)21)7-9-16-19(15,3)10-5-11-20(16,4)18(22)23/h6-7,12,15-16H,5,8-11H2,1-4H3,(H,22,23)/t15-,16+,19+,20+/m0/s1
SMILES CC(C)C1=CC[C@H]2C(=CC[C@@H]3[C@]2(C)CCC[C@@]3(C)C(=O)O)C1=O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   316.2 Volume:   344.632
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Van der Waals volume.
Dense:   0.918 LogP:   4.076
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.225
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.307
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The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
TPSA:   54.37
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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:   0.822 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.308 Fsp3:   0.7
MCE-18:   55.647
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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:   0.376 Fluc inhibitor:   0.038
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.026
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.001
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.765 Promiscuous compounds:   0.054

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.039 MDCK Permeability:   -4.993
Pgp-inhibitor:   0.454 Pgp-substrate:   0.006
PAMPA:   0.841
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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):   0.013
20% Bioavailability (F20%):   0.051 30% Bioavailability (F30%):   0.071
50% Bioavailability (F50%):   0.653

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.004 MRP1:   0.997
Plasma Protein Binding (PPB):   94.706% Volume Distribution (VD):   -0.182
Fu: 5.936%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.992 BCRP inhibitor:   0.005
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   0.151 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.333 CYP2C19-substrate:   0.002
CYP2C9-inhibitor:   0.02 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.009
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   0.185
CYP2B6-substrate:   0.001 CYP2C8-inhibitor:   0.853
HLM stability:   0.04
?
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):  2.967 Half-life (T1/2):  0.875

ADMET: Toxicity

hERG Blockers:  0.046 hERG Blockers (10um):  0.071
Human Hepatotoxicity (H-HT):  0.585 Drug-induced Liver Injury (DILI):  0.48
AMES Toxicity:  0.152 Rat Oral Acute Toxicity:  0.271
Maximum Recommended Daily Dose:  0.411 Skin Sensitization:  0.918
Carcinogencity:  0.68 Eye Corrosion:  0.697
Eye Irritation:  0.891 Respiratory Toxicity:  0.814
Drug-induced Neurotoxicity:  0.047 Ototoxicity:  0.483
Hematotoxicity:  0.478 Drug-induced Nephrotoxicity:  0.818
Genotoxicity:  0.439 RPMI-8226 Immunitoxicity:  0.045
A549 Cytotoxicity:  0.021 Hek293 Cytotoxicity:  0.067
BCF:   1.277
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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:   3.988
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.52
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.889
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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
NPO12422 Pinus massoniana Species Pinaceae Eukaryota n.a. n.a. n.a. PMID[32100544]
NPO12422 Pinus massoniana 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]
NPO12422 Pinus massoniana Species Pinaceae 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]
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
NPT1464 Individual protein Phosphodiesterase 4D Homo sapiens IC50 = 2800.0 nM PMID[32100544]

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 NPC484817 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
0.6731 Remote Similarity NPC102197
0.6275 Remote Similarity NPC480561
0.5965 Remote Similarity NPC72397
0.5926 Remote Similarity NPC192540
0.5849 Remote Similarity NPC610518
0.5636 Remote Similarity NPC59436
0.5636 Remote Similarity NPC109854
0.5536 Remote Similarity NPC302661
0.5455 Remote Similarity NPC237591
0.5455 Remote Similarity NPC3753
0.5439 Remote Similarity NPC82979
0.5345 Remote Similarity NPC483605
0.5333 Remote Similarity NPC24816
0.5254 Remote Similarity NPC144278
0.5254 Remote Similarity NPC94163
0.5172 Remote Similarity NPC90055
0.5172 Remote Similarity NPC606858
0.5088 Remote Similarity NPC165711

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC484817 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