Natural Product: NPC488650

Natural Product IDNPC488650
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 KUSFVCHTPOSQLS-JWLDURQRSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 127034480
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001551] Diterpenoids
          • [CHEMONTID:0001757] Colensane and clerodane 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 KUSFVCHTPOSQLS-JWLDURQRSA-N
Standard InCHI InChI=1S/C23H36O5/c1-8-14(2)9-10-22(4)15(3)11-19(25-5)23-17(12-16(24)13-18(22)23)20(26-6)28-21(23)27-7/h8,12,15-16,18-21,24H,1-2,9-11,13H2,3-7H3/t15-,16-,18+,19+,20+,21-,22-,23-/m1/s1
SMILES C=CC(=C)CC[C@]1(C)[C@H](C)C[C@@H]([C@@]23C(=C[C@H](C[C@@H]12)O)[C@@H](OC)O[C@H]3OC)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   392.26 Volume:   416.737
?
Van der Waals volume.
Dense:   0.941 LogP:   2.759
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.769
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.452
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   17.0
TPSA:   57.15
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.527 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.851 Fsp3:   0.739
MCE-18:   80.5
?
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:   0.459 Fluc inhibitor:   0.001
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.015
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.001
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.294 Promiscuous compounds:   0.208

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.043 MDCK Permeability:   -4.836
Pgp-inhibitor:   0.938 Pgp-substrate:   0.356
PAMPA:   0.175
?
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):   0.027
20% Bioavailability (F20%):   0.897 30% Bioavailability (F30%):   0.923
50% Bioavailability (F50%):   0.995

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.008 MRP1:   0.685
Plasma Protein Binding (PPB):   78.281% Volume Distribution (VD):   0.257
Fu: 23.543%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   0.983 BCRP inhibitor:   0.848
BSEP inhibitor:   0.948

ADMET: Metabolism

CYP1A2-inhibitor:   0.923 CYP1A2-substrate:   0.123
CYP2C19-inhibitor:   0.999 CYP2C19-substrate:   0.115
CYP2C9-inhibitor:   0.856 CYP2C9-substrate:   0.011
CYP2D6-inhibitor:   0.875 CYP2D6-substrate:   0.529
CYP3A4-inhibitor:   0.922 CYP3A4-substrate:   0.955
CYP2B6-substrate:   1.0 CYP2C8-inhibitor:   0.415
HLM stability:   0.982
?
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):  15.004 Half-life (T1/2):  2.247

ADMET: Toxicity

hERG Blockers:  0.234 hERG Blockers (10um):  0.623
Human Hepatotoxicity (H-HT):  0.535 Drug-induced Liver Injury (DILI):  0.52
AMES Toxicity:  0.798 Rat Oral Acute Toxicity:  0.923
Maximum Recommended Daily Dose:  0.984 Skin Sensitization:  0.931
Carcinogencity:  0.398 Eye Corrosion:  0.001
Eye Irritation:  0.568 Respiratory Toxicity:  0.991
Drug-induced Neurotoxicity:  0.764 Ototoxicity:  0.781
Hematotoxicity:  0.474 Drug-induced Nephrotoxicity:  0.611
Genotoxicity:  0.827 RPMI-8226 Immunitoxicity:  0.332
A549 Cytotoxicity:  0.159 Hek293 Cytotoxicity:  0.325
BCF:   0.681
?
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:   3.444
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.182
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.412
?
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
NPO32459 casearia balansae Species Salicaceae Eukaryota leaves and twigs n.a. n.a. PMID[24033131]
NPO32459 casearia balansae Species Salicaceae Eukaryota twigs n.a. n.a. PMID[25286284]
NPO32459 casearia balansae Species Salicaceae Eukaryota Leaves n.a. n.a. PMID[26699618]
NPO32459 casearia balansae Species Salicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

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
NPT681 Cell line PC-12 Rattus norvegicus EC50 = 5400.0 nM PMID[26699618]

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 NPC488650 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 NPC481022
0.8889 High Similarity NPC488651
0.8889 High Similarity NPC488648
0.6667 Remote Similarity NPC488221
0.6667 Remote Similarity NPC488220
0.6667 Remote Similarity NPC488216
0.6286 Remote Similarity NPC486752
0.6129 Remote Similarity NPC472189
0.6032 Remote Similarity NPC481018
0.5946 Remote Similarity NPC486759
0.5946 Remote Similarity NPC488217
0.5946 Remote Similarity NPC488218
0.5938 Remote Similarity NPC481020
0.5781 Remote Similarity NPC171598
0.5758 Remote Similarity NPC472188
0.5692 Remote Similarity NPC132395
0.5692 Remote Similarity NPC471364
0.5606 Remote Similarity NPC471362
0.5606 Remote Similarity NPC471372
0.5606 Remote Similarity NPC318917
0.5606 Remote Similarity NPC481019
0.5522 Remote Similarity NPC472186
0.5441 Remote Similarity NPC471366
0.5441 Remote Similarity NPC476800
0.5441 Remote Similarity NPC488649
0.5441 Remote Similarity NPC488237
0.5362 Remote Similarity NPC471365
0.5362 Remote Similarity NPC481017
0.5139 Remote Similarity NPC472187

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC488650 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