Natural Product: NPC90529

Natural Product IDNPC90529
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 PSUFRPOAICRSTC-FJHONVIPSA-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:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000219] Pyrrolizines

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 PSUFRPOAICRSTC-FJHONVIPSA-N
Standard InCHI InChI=1S/C16H23NO5/c1-9-14(18)21-8-11-4-6-17-7-5-12(13(11)17)22-15(19)10(2)16(9,3)20/h4,9-10,12-13,20H,5-8H2,1-3H3/t9-,10+,12+,13-,16-/m1/s1
SMILES C[C@@H]1C(=O)OCC2=CCN3CC[C@@H]([C@@H]23)OC(=O)[C@H](C)[C@]1(C)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   309.16 Volume:   306.661
?
Van der Waals volume.
Dense:   1.008 LogP:   0.227
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.593
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.773
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   20.0
TPSA:   76.07
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.518 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.109 Fsp3:   0.75
MCE-18:   52.857
?
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:   0.276 Fluc inhibitor:   0.009
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.158
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.014
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.007 Promiscuous compounds:   0.489

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.277 MDCK Permeability:   -4.969
Pgp-inhibitor:   0.065 Pgp-substrate:   0.907
PAMPA:   0.783
?
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):   0.002
20% Bioavailability (F20%):   0.049 30% Bioavailability (F30%):   0.33
50% Bioavailability (F50%):   0.537

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.012 MRP1:   0.978
Plasma Protein Binding (PPB):   38.625% Volume Distribution (VD):   -0.203
Fu: 58.78%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.994
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.026
BSEP inhibitor:   0.443

ADMET: Metabolism

CYP1A2-inhibitor:   0.777 CYP1A2-substrate:   0.003
CYP2C19-inhibitor:   0.885 CYP2C19-substrate:   0.003
CYP2C9-inhibitor:   0.267 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.001 CYP2D6-substrate:   0.003
CYP3A4-inhibitor:   0.143 CYP3A4-substrate:   0.612
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.012
HLM stability:   0.873
?
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):  3.808 Half-life (T1/2):  2.906

ADMET: Toxicity

hERG Blockers:  0.015 hERG Blockers (10um):  0.202
Human Hepatotoxicity (H-HT):  0.823 Drug-induced Liver Injury (DILI):  0.809
AMES Toxicity:  0.563 Rat Oral Acute Toxicity:  0.508
Maximum Recommended Daily Dose:  0.731 Skin Sensitization:  1.0
Carcinogencity:  0.971 Eye Corrosion:  0.074
Eye Irritation:  0.663 Respiratory Toxicity:  0.761
Drug-induced Neurotoxicity:  0.906 Ototoxicity:  0.279
Hematotoxicity:  0.468 Drug-induced Nephrotoxicity:  0.924
Genotoxicity:  0.994 RPMI-8226 Immunitoxicity:  0.174
A549 Cytotoxicity:  0.267 Hek293 Cytotoxicity:  0.616
BCF:   0.415
?
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:   3.026
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.37
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.696
?
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
NPO14579 Mentha spicata Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[12776552]
NPO14579 Mentha spicata Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[36715796]
NPO9494 Ambrosia confertiflora Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12968 Crotalaria spectabilis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14579 Mentha spicata Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14579 Mentha spicata Species Lamiaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO14579 Mentha spicata Species Lamiaceae Eukaryota n.a. n.a. Database[FooDB]
NPO14579 Mentha spicata Species Lamiaceae Eukaryota n.a. n.a. Database[FooDB]
NPO14579 Mentha spicata Species Lamiaceae Eukaryota Shoot n.a. n.a. Database[FooDB]
NPO14579 Mentha spicata Species Lamiaceae Eukaryota Plant n.a. n.a. Database[FooDB]
NPO14579 Mentha spicata Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO9494 Ambrosia confertiflora Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12968 Crotalaria spectabilis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14579 Mentha spicata Species Lamiaceae Eukaryota n.a. n.a. Database[Phenol-Explorer]
NPO14579 Mentha spicata Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12968 Crotalaria spectabilis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO9494 Ambrosia confertiflora Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12968 Crotalaria spectabilis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9494 Ambrosia confertiflora Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14579 Mentha spicata 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 NPC90529 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
0.7636 Intermediate Similarity NPC30911
0.7018 Intermediate Similarity NPC608092
0.6557 Remote Similarity NPC316984
0.6333 Remote Similarity NPC130124
0.6333 Remote Similarity NPC193471
0.6333 Remote Similarity NPC608663
0.623 Remote Similarity NPC608751
0.6129 Remote Similarity NPC47857
0.6129 Remote Similarity NPC181510
0.6129 Remote Similarity NPC168758
0.6129 Remote Similarity NPC602310
0.6129 Remote Similarity NPC609037
0.6032 Remote Similarity NPC23963
0.6032 Remote Similarity NPC201889
0.6032 Remote Similarity NPC106791
0.6032 Remote Similarity NPC607716
0.6032 Remote Similarity NPC608959
0.5556 Remote Similarity NPC610562
0.5522 Remote Similarity NPC600980

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC90529 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
0.7636 Intermediate Similarity NPD2204 Approved

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