Natural Product: NPC187100

Natural Product IDNPC187100
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 UABBYTGYXLXVNA-MPBGBICISA-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:0000279] Alkaloids and derivatives
      • [CHEMONTID:0001909] Protoberberine alkaloids and derivatives

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 UABBYTGYXLXVNA-MPBGBICISA-N
Standard InCHI InChI=1S/C21H25NO4/c1-12-14-5-6-18(24-2)21(26-4)16(14)11-22-8-7-13-9-19(25-3)17(23)10-15(13)20(12)22/h5-6,9-10,12,20,23H,7-8,11H2,1-4H3/t12-,20-/m1/s1
SMILES C[C@@H]1c2ccc(c(c2CN2CCc3cc(c(cc3[C@@H]12)O)OC)OC)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   355.18 Volume:   367.885
?
Van der Waals volume.
Dense:   0.965 LogP:   2.293
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.573
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.992
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The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   21.0
TPSA:   51.16
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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:   0.911 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.355 Fsp3:   0.429
MCE-18:   76.667
?
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:   0.22 Fluc inhibitor:   0.073
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.71
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.397
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.001 Promiscuous compounds:   0.155

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.945 MDCK Permeability:   -4.804
Pgp-inhibitor:   0.543 Pgp-substrate:   0.488
PAMPA:   0.007
?
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):   0.001
20% Bioavailability (F20%):   0.192 30% Bioavailability (F30%):   0.217
50% Bioavailability (F50%):   0.959

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.361 MRP1:   0.967
Plasma Protein Binding (PPB):   92.794% Volume Distribution (VD):   -0.069
Fu: 7.365%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.994
OATP1B3 inhibitor:   0.997 BCRP inhibitor:   0.797
BSEP inhibitor:   0.962

ADMET: Metabolism

CYP1A2-inhibitor:   0.998 CYP1A2-substrate:   0.114
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.005
CYP2C9-inhibitor:   0.944 CYP2C9-substrate:   0.997
CYP2D6-inhibitor:   0.995 CYP2D6-substrate:   0.664
CYP3A4-inhibitor:   0.966 CYP3A4-substrate:   0.96
CYP2B6-substrate:   0.809 CYP2C8-inhibitor:   0.858
HLM stability:   0.914
?
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):  6.327 Half-life (T1/2):  1.974

ADMET: Toxicity

hERG Blockers:  0.341 hERG Blockers (10um):  0.682
Human Hepatotoxicity (H-HT):  0.577 Drug-induced Liver Injury (DILI):  0.219
AMES Toxicity:  0.598 Rat Oral Acute Toxicity:  0.549
Maximum Recommended Daily Dose:  0.551 Skin Sensitization:  0.618
Carcinogencity:  0.654 Eye Corrosion:  0.004
Eye Irritation:  0.511 Respiratory Toxicity:  0.8
Drug-induced Neurotoxicity:  0.689 Ototoxicity:  0.552
Hematotoxicity:  0.352 Drug-induced Nephrotoxicity:  0.397
Genotoxicity:  0.565 RPMI-8226 Immunitoxicity:  0.094
A549 Cytotoxicity:  0.336 Hek293 Cytotoxicity:  0.51
BCF:   1.63
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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:   3.991
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.331
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.667
?
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
NPO29263 Tylopilus plumbeoviolaceus Species Boletaceae Eukaryota n.a. fruit body n.a. PMID[10785434]
NPO29086 Dovyalis hebecarpa Species Salicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29246 Ixeris repens Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29263 Tylopilus plumbeoviolaceus Species Boletaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29206 Lycopodium chinense Species Lycopodiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29441 Eremophila oppositifolia Species Scrophulariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28926 Corydalis tuberosa Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17311 Penicillium vulpinum Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28926 Corydalis tuberosa Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28926 Corydalis tuberosa Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28926 Corydalis tuberosa Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29206 Lycopodium chinense Species Lycopodiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29263 Tylopilus plumbeoviolaceus Species Boletaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29246 Ixeris repens Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29086 Dovyalis hebecarpa Species Salicaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29490 Taxillus yadoriki Species Loranthaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29441 Eremophila oppositifolia Species Scrophulariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17311 Penicillium vulpinum Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29347 Hydnum aurantiacum Species Hydnaceae 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 NPC187100 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
0.7627 Intermediate Similarity NPC7467
0.6984 Remote Similarity NPC295691
0.6984 Remote Similarity NPC207757
0.6984 Remote Similarity NPC54379
0.6418 Remote Similarity NPC146288
0.6212 Remote Similarity NPC204828
0.6212 Remote Similarity NPC5238
0.5915 Remote Similarity NPC232514
0.5672 Remote Similarity NPC189266
0.5672 Remote Similarity NPC2413
0.5672 Remote Similarity NPC110416
0.5385 Remote Similarity NPC88249
0.5362 Remote Similarity NPC249797
0.5362 Remote Similarity NPC193949
0.5075 Remote Similarity NPC210437
0.5075 Remote Similarity NPC16107
0.5075 Remote Similarity NPC106295

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC187100 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
0.5075 Remote Similarity NPD4584 Phase 2

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