Natural Product: NPC294599

Natural Product IDNPC294599
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 JTJZAWZRQPNBLR-MZGDTODISA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 101285934
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001551] Diterpenoids
          • [CHEMONTID:0003782] Kaurane 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 JTJZAWZRQPNBLR-MZGDTODISA-N
Standard InCHI InChI=1S/C20H32/c1-17(2)7-5-8-18(3)15(17)6-9-20-11-14-13(10-16(18)20)19(14,4)12-20/h13-16H,5-12H2,1-4H3/t13-,14+,15-,16+,18-,19-,20+/m1/s1
SMILES CC1(C)CCC[C@]2(C)[C@@H]1CC[C@]13C[C@H]4[C@@H](C[C@@H]23)[C@@]4(C)C1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   272.25 Volume:   311.694
?
Van der Waals volume.
Dense:   0.873 LogP:   4.968
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.858
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.426
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   20.0
TPSA:   0.0
?
Topological Polar Surface Area.
 H-Bond Acceptor:   0.0
H-Bond Donor:   0.0 Rings:   6.0
Heavy Atoms:   0.0

MedChem Properties

QED Drug-Likeness Score:   0.533 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.96 Fsp3:   1.0
MCE-18:   117.8
?
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:   0.551 Fluc inhibitor:   0.031
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.004
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.0
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.752 Promiscuous compounds:   0.077

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.537 MDCK Permeability:   -4.836
Pgp-inhibitor:   0.982 Pgp-substrate:   0.006
PAMPA:   0.013
?
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):   0.007
20% Bioavailability (F20%):   0.237 30% Bioavailability (F30%):   0.187
50% Bioavailability (F50%):   0.575

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.714 MRP1:   0.727
Plasma Protein Binding (PPB):   98.461% Volume Distribution (VD):   0.56
Fu: 2.425%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.996
OATP1B3 inhibitor:   0.939 BCRP inhibitor:   0.171
BSEP inhibitor:   0.997

ADMET: Metabolism

CYP1A2-inhibitor:   0.727 CYP1A2-substrate:   0.007
CYP2C19-inhibitor:   0.999 CYP2C19-substrate:   0.893
CYP2C9-inhibitor:   0.036 CYP2C9-substrate:   0.072
CYP2D6-inhibitor:   0.964 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.842 CYP2C8-inhibitor:   0.911
HLM stability:   0.041
?
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):  12.902 Half-life (T1/2):  0.709

ADMET: Toxicity

hERG Blockers:  0.117 hERG Blockers (10um):  0.451
Human Hepatotoxicity (H-HT):  0.619 Drug-induced Liver Injury (DILI):  0.082
AMES Toxicity:  0.249 Rat Oral Acute Toxicity:  0.397
Maximum Recommended Daily Dose:  0.682 Skin Sensitization:  0.928
Carcinogencity:  0.804 Eye Corrosion:  0.54
Eye Irritation:  0.882 Respiratory Toxicity:  0.885
Drug-induced Neurotoxicity:  0.323 Ototoxicity:  0.426
Hematotoxicity:  0.451 Drug-induced Nephrotoxicity:  0.622
Genotoxicity:  0.057 RPMI-8226 Immunitoxicity:  0.033
A549 Cytotoxicity:  0.138 Hek293 Cytotoxicity:  0.245
BCF:   3.492
?
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:   4.998
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.314
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.996
?
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
NPO3497 Pestalotiopsis virgatula Species Sporocadaceae Eukaryota n.a. mycelium n.a. PMID[21942847]
NPO11287 Sideritis lotsyi Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3497 Pestalotiopsis virgatula Species Sporocadaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9377 Ormosia elata Species Limoniidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11159 Isoplexis chalcantha Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5068 Hyrtios eubamma Species Thorectidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO150 Echinops niveus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1778 Corydalis claviculata Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11050 Cladonia amaurocraea Species Cladoniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6630 Cetraria pinastri Species Parmeliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2126 Asterias forbesi Species Asteriidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1778 Corydalis claviculata Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO1778 Corydalis claviculata Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11159 Isoplexis chalcantha Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2126 Asterias forbesi Species Asteriidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3497 Pestalotiopsis virgatula Species Sporocadaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO150 Echinops niveus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6630 Cetraria pinastri Species Parmeliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11050 Cladonia amaurocraea Species Cladoniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9377 Ormosia elata Species Limoniidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5068 Hyrtios eubamma Species Thorectidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1778 Corydalis claviculata Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11287 Sideritis lotsyi Species Lamiaceae 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

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 NPC294599 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
0.7368 Intermediate Similarity NPC483371
0.7368 Intermediate Similarity NPC483372
0.561 Remote Similarity NPC474105
0.561 Remote Similarity NPC473276
0.561 Remote Similarity NPC483380
0.561 Remote Similarity NPC474380
0.5349 Remote Similarity NPC475884
0.5349 Remote Similarity NPC473230
0.525 Remote Similarity NPC609214
0.5111 Remote Similarity NPC130459
0.5111 Remote Similarity NPC483379
0.5111 Remote Similarity NPC473267
0.5111 Remote Similarity NPC474221

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC294599 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