Natural Product: NPC5597

Natural Product IDNPC5597
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 NLSPLEIAOWRBOI-SIKIZQCASA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 5317151
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001283] Terpene lactones
          • [CHEMONTID:0001538] Diterpene lactones

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 NLSPLEIAOWRBOI-SIKIZQCASA-N
Standard InCHI InChI=1S/C20H24O3/c1-14-6-10-20-13-23-18(21)16(20)4-3-5-17(20)19(14,2)9-7-15-8-11-22-12-15/h3-5,8,11-12,14,17H,6-7,9-10,13H2,1-2H3/t14-,17-,19+,20-/m1/s1
SMILES C[C@@H]1CC[C@@]23COC(=O)C2=CC=C[C@@H]3[C@@]1(C)CCc1ccoc1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   312.17 Volume:   333.439
?
Van der Waals volume.
Dense:   0.936 LogP:   3.269
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.215
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.631
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   21.0
TPSA:   39.44
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   0.0 Rings:   4.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.781 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.074 Fsp3:   0.55
MCE-18:   102.387
?
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:   0.563 Fluc inhibitor:   0.391
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.037
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.012
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.524 Promiscuous compounds:   0.093

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.7 MDCK Permeability:   -4.53
Pgp-inhibitor:   0.922 Pgp-substrate:   0.581
PAMPA:   0.401
?
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):   0.024
20% Bioavailability (F20%):   0.672 30% Bioavailability (F30%):   0.795
50% Bioavailability (F50%):   0.852

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.76 MRP1:   0.579
Plasma Protein Binding (PPB):   95.832% Volume Distribution (VD):   -0.044
Fu: 3.823%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.926
OATP1B3 inhibitor:   0.474 BCRP inhibitor:   0.789
BSEP inhibitor:   0.979

ADMET: Metabolism

CYP1A2-inhibitor:   0.005 CYP1A2-substrate:   0.445
CYP2C19-inhibitor:   0.934 CYP2C19-substrate:   0.654
CYP2C9-inhibitor:   0.009 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.467
CYP3A4-inhibitor:   0.999 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.001 CYP2C8-inhibitor:   1.0
HLM stability:   0.887
?
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):  5.23 Half-life (T1/2):  1.031

ADMET: Toxicity

hERG Blockers:  0.293 hERG Blockers (10um):  0.557
Human Hepatotoxicity (H-HT):  0.805 Drug-induced Liver Injury (DILI):  0.873
AMES Toxicity:  0.817 Rat Oral Acute Toxicity:  0.842
Maximum Recommended Daily Dose:  0.951 Skin Sensitization:  0.901
Carcinogencity:  0.963 Eye Corrosion:  0.002
Eye Irritation:  0.734 Respiratory Toxicity:  0.621
Drug-induced Neurotoxicity:  0.414 Ototoxicity:  0.414
Hematotoxicity:  0.692 Drug-induced Nephrotoxicity:  0.784
Genotoxicity:  0.976 RPMI-8226 Immunitoxicity:  0.172
A549 Cytotoxicity:  0.29 Hek293 Cytotoxicity:  0.382
BCF:   2.013
?
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:   4.193
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.475
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.117
?
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
NPO16484 Muraltia heisteria Species Polygalaceae Eukaryota n.a. n.a. n.a. PMID[11858755]
NPO17691 Santalum album Species Santalaceae Eukaryota n.a. n.a. n.a. PMID[15974602]
NPO17462 Pouteria sapota Species Sapotaceae Eukaryota n.a. ripe fruit n.a. PMID[21214217]
NPO2286 Fischerella muscicola Species Hapalosiphonaceae Bacteria n.a. n.a. n.a. PMID[22863526]
NPO17620 Rhodopirellula baltica Species Planctomycetaceae Bacteria n.a. n.a. n.a. PMID[23826385]
NPO17462 Pouteria sapota Species Sapotaceae Eukaryota n.a. n.a. n.a. PMID[26057604]
NPO669 Crepis pygmaea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17462 Pouteria sapota Species Sapotaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17691 Santalum album Species Santalaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14039 Leucaena leucocephala Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9405 Siphocampylus foliosus Species Campanulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2286 Fischerella muscicola Species Hapalosiphonaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO16065 Micromeria japonica Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16484 Muraltia heisteria Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16352 Peperomia villipetiola Species Piperaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15771 Polygonatum prattii Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17620 Rhodopirellula baltica Species Planctomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO17155 Selaginella apoda Species Selaginellaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15031 Senecio microglossus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17462 Pouteria sapota Species Sapotaceae Eukaryota n.a. n.a. Database[FooDB]
NPO17691 Santalum album Species Santalaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14039 Leucaena leucocephala Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17691 Santalum album Species Santalaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15771 Polygonatum prattii Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17691 Santalum album Species Santalaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO17691 Santalum album Species Santalaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO9405 Siphocampylus foliosus Species Campanulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO669 Crepis pygmaea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16065 Micromeria japonica Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16352 Peperomia villipetiola Species Piperaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17620 Rhodopirellula baltica Species Planctomycetaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO14039 Leucaena leucocephala Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17462 Pouteria sapota Species Sapotaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15031 Senecio microglossus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15771 Polygonatum prattii Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17155 Selaginella apoda Species Selaginellaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16484 Muraltia heisteria Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17691 Santalum album Species Santalaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2286 Fischerella muscicola Species Hapalosiphonaceae Bacteria 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 NPC5597 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
0.6923 Remote Similarity NPC601629
0.6197 Remote Similarity NPC303842
0.5357 Remote Similarity NPC161519
0.5286 Remote Similarity NPC289537
0.5263 Remote Similarity NPC485295
0.5263 Remote Similarity NPC485298
0.5132 Remote Similarity NPC90953

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC5597 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