Natural Product: NPC225718

Natural Product IDNPC225718
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 WGBOKYJTQKZKKN-OAHLLOKOSA-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:0002955] Tetrahydroisoquinolines

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 WGBOKYJTQKZKKN-OAHLLOKOSA-N
Standard InCHI InChI=1S/C19H21NO4/c1-20-6-5-13-9-18(22-2)16(21)10-14(13)15(20)7-12-3-4-17-19(8-12)24-11-23-17/h3-4,8-10,15,21H,5-7,11H2,1-2H3/t15-/m1/s1
SMILES CN1CCc2cc(c(cc2[C@H]1Cc1ccc2c(c1)OCO2)O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   327.15 Volume:   333.293
?
Van der Waals volume.
Dense:   0.982 LogP:   2.53
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.433
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.379
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   21.0
TPSA:   51.16
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.939 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.844 Fsp3:   0.368
MCE-18:   69.462
?
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:   1 PAINS Alert:   0
Colloidal aggregators:   0.475 Fluc inhibitor:   0.326
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.39
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.317
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.005 Promiscuous compounds:   0.367

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.789 MDCK Permeability:   -4.642
Pgp-inhibitor:   0.9 Pgp-substrate:   0.013
PAMPA:   0.014
?
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):   0.0
20% Bioavailability (F20%):   0.245 30% Bioavailability (F30%):   0.003
50% Bioavailability (F50%):   0.901

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.992 MRP1:   0.945
Plasma Protein Binding (PPB):   73.212% Volume Distribution (VD):   0.065
Fu: 32.835%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.994
OATP1B3 inhibitor:   0.973 BCRP inhibitor:   0.253
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.022
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   1.0
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.973
CYP3A4-inhibitor:   0.861 CYP3A4-substrate:   0.618
CYP2B6-substrate:   1.0 CYP2C8-inhibitor:   0.0
HLM stability:   0.204
?
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):  4.969 Half-life (T1/2):  2.083

ADMET: Toxicity

hERG Blockers:  0.426 hERG Blockers (10um):  0.59
Human Hepatotoxicity (H-HT):  0.748 Drug-induced Liver Injury (DILI):  0.271
AMES Toxicity:  0.655 Rat Oral Acute Toxicity:  0.327
Maximum Recommended Daily Dose:  0.851 Skin Sensitization:  0.6
Carcinogencity:  0.66 Eye Corrosion:  0.003
Eye Irritation:  0.694 Respiratory Toxicity:  0.577
Drug-induced Neurotoxicity:  0.798 Ototoxicity:  0.564
Hematotoxicity:  0.188 Drug-induced Nephrotoxicity:  0.283
Genotoxicity:  0.732 RPMI-8226 Immunitoxicity:  0.075
A549 Cytotoxicity:  0.138 Hek293 Cytotoxicity:  0.552
BCF:   1.487
?
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:   3.819
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.325
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.477
?
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
NPO20958 Smenospongia aurea Species Thorectidae Eukaryota n.a. Jamaican n.a. PMID[11975483]
NPO20254 Ipomoea leptophylla Species Convolvulaceae Eukaryota n.a. n.a. n.a. PMID[14640518]
NPO22556 Dendrolobium lanceolatum Species Fabaceae Eukaryota n.a. root n.a. PMID[15217275]
NPO927 Swertia mussotii Species Gentianaceae Eukaryota n.a. n.a. n.a. PMID[19645233]
NPO18680 Larix decidua Species Pinaceae Eukaryota n.a. n.a. n.a. PMID[38259911]
NPO927 Swertia mussotii Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[Article]
NPO20254 Ipomoea leptophylla Species Convolvulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO927 Swertia mussotii Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22817 Actinidia valvata Species Actinidiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18680 Larix decidua Species Pinaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21026 Pericopsis mooniana Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20958 Smenospongia aurea Species Thorectidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO927 Swertia mussotii Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO927 Swertia mussotii Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO22556 Dendrolobium lanceolatum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14326 Pseudocercospora fijiensis Species Mycosphaerellaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21026 Pericopsis mooniana Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO927 Swertia mussotii Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18257 Oberna wallichiana n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO22495 Cladonia alpestris Species Cladoniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21848 Rosa hybr Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18680 Larix decidua Species Pinaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20254 Ipomoea leptophylla Species Convolvulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22817 Actinidia valvata Species Actinidiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17360 Argemone albiflora Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20958 Smenospongia aurea Species Thorectidae 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 NPC225718 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
0.7586 Intermediate Similarity NPC147390
0.7586 Intermediate Similarity NPC428
0.6912 Remote Similarity NPC480592
0.6885 Remote Similarity NPC321505
0.6885 Remote Similarity NPC179825
0.6714 Remote Similarity NPC603603
0.6613 Remote Similarity NPC135538
0.6613 Remote Similarity NPC24233
0.6389 Remote Similarity NPC240841
0.6267 Remote Similarity NPC286119
0.6167 Remote Similarity NPC213206
0.6167 Remote Similarity NPC188163
0.6167 Remote Similarity NPC328750
0.6143 Remote Similarity NPC232514
0.5946 Remote Similarity NPC610959
0.5938 Remote Similarity NPC191376
0.5873 Remote Similarity NPC111485
0.5844 Remote Similarity NPC600872
0.5588 Remote Similarity NPC27887
0.5588 Remote Similarity NPC475959
0.5507 Remote Similarity NPC295691
0.5507 Remote Similarity NPC207757
0.5507 Remote Similarity NPC54379
0.5488 Remote Similarity NPC601489
0.5488 Remote Similarity NPC604804
0.5484 Remote Similarity NPC314682
0.5417 Remote Similarity NPC317272
0.5417 Remote Similarity NPC268503
0.5385 Remote Similarity NPC185838
0.5316 Remote Similarity NPC609914
0.525 Remote Similarity NPC311973
0.525 Remote Similarity NPC239824
0.5238 Remote Similarity NPC24260
0.5231 Remote Similarity NPC185467
0.52 Remote Similarity NPC256012
0.52 Remote Similarity NPC610965
0.519 Remote Similarity NPC290582
0.519 Remote Similarity NPC217748
0.519 Remote Similarity NPC73492
0.519 Remote Similarity NPC182052
0.519 Remote Similarity NPC271013
0.519 Remote Similarity NPC299990
0.519 Remote Similarity NPC42663
0.519 Remote Similarity NPC15414
0.5185 Remote Similarity NPC254441
0.5152 Remote Similarity NPC88249
0.5143 Remote Similarity NPC249797
0.5143 Remote Similarity NPC247639
0.5143 Remote Similarity NPC193949
0.5143 Remote Similarity NPC25084
0.5125 Remote Similarity NPC279228
0.5075 Remote Similarity NPC609731
0.5068 Remote Similarity NPC276944
0.5068 Remote Similarity NPC238530
0.5067 Remote Similarity NPC229166

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC225718 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
0.6167 Remote Similarity NPD4664 Clinical (unspecified phase)
0.597 Remote Similarity NPD4010 Discontinued

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