Natural Product: NPC293871

Natural Product IDNPC293871
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 AIXQQSTVOSFSMO-RBOXIYTFSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1385
PubChem CID 9838394
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000279] Alkaloids and derivatives
      • [CHEMONTID:0001775] Amaryllidaceae alkaloids
        • [CHEMONTID:0004128] Galanthamine-type amaryllidaceae alkaloids

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 AIXQQSTVOSFSMO-RBOXIYTFSA-N
Standard InCHI InChI=1S/C16H19NO3/c1-19-12-3-2-10-9-17-7-6-16-5-4-11(18)8-13(16)20-15(12)14(10)16/h2-5,11,13,17-18H,6-9H2,1H3/t11-,13-,16-/m0/s1
SMILES COc1ccc2c3c1O[C@@H]1[C@@]3(CCNC2)C=C[C@@H](C1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   273.14 Volume:   277.888
?
Van der Waals volume.
Dense:   0.983 LogP:   0.252
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.63
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.724
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   20.0
TPSA:   50.72
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.762 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.37 Fsp3:   0.5
MCE-18:   96.25
?
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:   0.47 Fluc inhibitor:   0.004
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.066
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.097
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.004 Promiscuous compounds:   0.173

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.866 MDCK Permeability:   -4.941
Pgp-inhibitor:   0.041 Pgp-substrate:   0.829
PAMPA:   0.317
?
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%):   0.004 30% Bioavailability (F30%):   0.046
50% Bioavailability (F50%):   0.049

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.994 MRP1:   0.795
Plasma Protein Binding (PPB):   18.122% Volume Distribution (VD):   0.285
Fu: 77.322%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.831
OATP1B3 inhibitor:   0.405 BCRP inhibitor:   0.063
BSEP inhibitor:   0.925

ADMET: Metabolism

CYP1A2-inhibitor:   0.091 CYP1A2-substrate:   0.001
CYP2C19-inhibitor:   0.074 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.373
CYP2D6-inhibitor:   0.88 CYP2D6-substrate:   0.027
CYP3A4-inhibitor:   0.331 CYP3A4-substrate:   0.143
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.002
HLM stability:   0.03
?
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):  5.026 Half-life (T1/2):  4.195

ADMET: Toxicity

hERG Blockers:  0.295 hERG Blockers (10um):  0.412
Human Hepatotoxicity (H-HT):  0.862 Drug-induced Liver Injury (DILI):  0.72
AMES Toxicity:  0.513 Rat Oral Acute Toxicity:  0.738
Maximum Recommended Daily Dose:  0.762 Skin Sensitization:  0.676
Carcinogencity:  0.462 Eye Corrosion:  0.403
Eye Irritation:  0.921 Respiratory Toxicity:  0.99
Drug-induced Neurotoxicity:  0.759 Ototoxicity:  0.536
Hematotoxicity:  0.488 Drug-induced Nephrotoxicity:  0.92
Genotoxicity:  0.559 RPMI-8226 Immunitoxicity:  0.098
A549 Cytotoxicity:  0.102 Hek293 Cytotoxicity:  0.153
BCF:   0.449
?
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:   3.121
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.684
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.874
?
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
NPO27062 Narcissus pseudonarcissus Species Amaryllidaceae Eukaryota n.a. bulb n.a. PMID[21105682]
NPO27303 Mikania alvimii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO389 Actaea heracleifolia Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1412 Artemisia juncea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9144 Atriplex parvifolia Species Chenopodiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9927 Crinum asiaticum Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3630 Crotalaria crispata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11000 Eupatorium laevigatum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9485 Haplopappus deserticola Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19776 Hesperocyparis arizonica Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11473 Viburnum lantana Species Adoxaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27062 Narcissus pseudonarcissus Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27776 Lycoris guangxiensis Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26154 Erythropodium caribaeorum Species Anthothelidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO272 Pittosporum eugenioides Species Pittosporaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26641 Pteroxygonum giraldii Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13480 Stereocaulon dactylophyllum Species Stereocaulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9228.1 Narcissus pseudonarcissus subsp. leonensis Subspecies Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19610 Stachys aegyptiaca Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11294 Launaea mucronata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26875 Hemizonia lobbii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13181 Ferula persica Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27044 Phebalium squameum Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26604 Aralia subcapitata Species Araliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9927.1 Crinum asiaticum var. japonicum Varieties Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO29312 Galanthus elwelii Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11389 Narcissus nivalis Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO29988 Narcissus leonensis Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO3630 Crotalaria crispata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO27776 Lycoris guangxiensis Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO27062 Narcissus pseudonarcissus Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO9927 Crinum asiaticum Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19490 Hymenocallis rotata Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO389 Actaea heracleifolia Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO9927.1 Crinum asiaticum var. japonicum Varieties Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27062.1 Narcissus pseudonarcissus ssp. pseudonarcissus n.a. Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO26604 Aralia subcapitata Species Araliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO19490 Hymenocallis rotata Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27776 Lycoris guangxiensis Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11389 Narcissus nivalis Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO9927 Crinum asiaticum Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO9228.1 Narcissus pseudonarcissus subsp. leonensis Subspecies Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29312 Galanthus elwelii Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3630 Crotalaria crispata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27062 Narcissus pseudonarcissus Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27776 Lycoris guangxiensis Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO389 Actaea heracleifolia Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO26154 Erythropodium caribaeorum Species Anthothelidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13181 Ferula persica Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26604 Aralia subcapitata Species Araliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11000 Eupatorium laevigatum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO272 Pittosporum eugenioides Species Pittosporaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19776 Hesperocyparis arizonica Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1412 Artemisia juncea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9927 Crinum asiaticum Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11389 Narcissus nivalis Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3630 Crotalaria crispata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11294 Launaea mucronata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17432 Ligularia przewalskii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9144 Atriplex parvifolia Species Chenopodiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9485 Haplopappus deserticola Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26641 Pteroxygonum giraldii Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11473 Viburnum lantana Species Adoxaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO389 Actaea heracleifolia Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9228.1 Narcissus pseudonarcissus subsp. leonensis Subspecies Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27303 Mikania alvimii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27776 Lycoris guangxiensis Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26299 Reticularia lycoperdon Species Reticulariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19610 Stachys aegyptiaca Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13480 Stereocaulon dactylophyllum Species Stereocaulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19490 Hymenocallis rotata Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27062 Narcissus pseudonarcissus Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27250 Teucrium belion Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26875 Hemizonia lobbii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27209 Sarcina litoralis Species Clostridiaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO27263 Aeonium lindleyi Species Crassulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27044 Phebalium squameum Species Rutaceae 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
NPT204 Individual protein Acetylcholinesterase Homo sapiens IC50 = 1070.0 nM PMID[15878275]
NPT204 Individual protein Acetylcholinesterase Homo sapiens IC50 = 0.29 ug.mL-1 PMID[15878275]

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 NPC293871 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 NPC124433
0.5139 Remote Similarity NPC148014
0.5139 Remote Similarity NPC315707
0.5139 Remote Similarity NPC78359
0.5068 Remote Similarity NPC607345
0.5068 Remote Similarity NPC611663

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC293871 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
0.5139 Remote Similarity NPD2563 Phase 4
0.5068 Remote Similarity NPD2560 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