Natural Product: NPC106937

Natural Product IDNPC106937
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Psilocybine
IUPAC Name [3-[2-(dimethylamino)ethyl]-1H-indol-4-yl] dihydrogen phosphate
Synonyms CY-39; Psilocybine
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL194378
PubChem CID 10624
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000211] Indoles and derivatives
        • [CHEMONTID:0000183] Tryptamines 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 QVDSEJDULKLHCG-UHFFFAOYSA-N
Standard InCHI InChI=1S/C12H17N2O4P/c1-14(2)7-6-9-8-13-10-4-3-5-11(12(9)10)18-19(15,16)17/h3-5,8,13H,6-7H2,1-2H3,(H2,15,16,17)
SMILES CN(CCc1c[nH]c2c1c(ccc2)OP(=O)(O)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   284.09 Volume:   265.431
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Van der Waals volume.
Dense:   1.07 LogP:   -0.442
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.552
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.439
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The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   11.0
TPSA:   85.79
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Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   3.0 Rings:   2.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.728 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.636 Fsp3:   0.333
MCE-18:   14.0
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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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.096 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.158
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.213
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.014 Promiscuous compounds:   0.386

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.502 MDCK Permeability:   -5.054
Pgp-inhibitor:   0.003 Pgp-substrate:   0.028
PAMPA:   0.47
?
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):   0.003
20% Bioavailability (F20%):   0.007 30% Bioavailability (F30%):   0.146
50% Bioavailability (F50%):   0.95

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.911 MRP1:   0.468
Plasma Protein Binding (PPB):   25.817% Volume Distribution (VD):   -0.018
Fu: 79.669%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.374
OATP1B3 inhibitor:   0.913 BCRP inhibitor:   0.626
BSEP inhibitor:   0.079

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.99 CYP2C9-substrate:   0.571
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.0
HLM stability:   0.987
?
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):  5.404 Half-life (T1/2):  2.263

ADMET: Toxicity

hERG Blockers:  0.41 hERG Blockers (10um):  0.455
Human Hepatotoxicity (H-HT):  0.832 Drug-induced Liver Injury (DILI):  0.653
AMES Toxicity:  0.085 Rat Oral Acute Toxicity:  0.601
Maximum Recommended Daily Dose:  0.973 Skin Sensitization:  0.961
Carcinogencity:  0.206 Eye Corrosion:  0.205
Eye Irritation:  0.481 Respiratory Toxicity:  0.998
Drug-induced Neurotoxicity:  0.433 Ototoxicity:  0.087
Hematotoxicity:  0.169 Drug-induced Nephrotoxicity:  0.956
Genotoxicity:  0.993 RPMI-8226 Immunitoxicity:  0.088
A549 Cytotoxicity:  0.014 Hek293 Cytotoxicity:  0.084
BCF:   0.163
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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:   2.718
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.149
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.325
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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
NPO19207 Anthenea chinensis Species n.a. n.a. n.a. at a depth of 2-20 m, Sanya Bay in the South China Sea 2007-OCT PMID[20184290]
NPO29771 Psilocybe Genus Strophariaceae Eukaryota n.a. n.a. n.a. PMID[25007546]
NPO19021 Linaria vulgaris Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20409 Mostuea buchholzii Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20741 Artemisia hispanica Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19021 Linaria vulgaris Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19021 Linaria vulgaris Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO19021 Linaria vulgaris Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO21155 Coleophoma crateriformis Species n.a. Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19021 Linaria vulgaris Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20409 Mostuea buchholzii Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5920 Phegopteris decursivipinnata Species Thelypteridaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20549 Ulmus rubra Species Ulmaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20741 Artemisia hispanica Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19207 Anthenea chinensis Species n.a. n.a. 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
NPT290 Individual protein Serotonin 2a (5-HT2a) receptor Homo sapiens EC50 = 3475.0 nM PMID[16061378]
NPT291 Individual protein Serotonin 2b (5-HT2b) receptor Homo sapiens EC50 = 74.0 nM PMID[16061378]
NPT292 Individual protein Serotonin 2c (5-HT2c) receptor Homo sapiens EC50 = 506.0 nM PMID[16061378]
NPT290 Individual protein Serotonin 2a (5-HT2a) receptor Homo sapiens Emax = -34.0 % PMID[38505858]
NPT291 Individual protein Serotonin 2b (5-HT2b) receptor Homo sapiens Ki = 98.7 nM PMID[38516602]
NPT290 Individual protein Serotonin 2a (5-HT2a) receptor Homo sapiens Ki > 10000.0 nM PMID[38516602]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT28697 Cell line A 172 Homo sapiens Activity n.a. n.a. n.a. PMID[38505854]
NPT28438 Unchecked Unchecked n.a. Activity n.a. n.a. n.a. PMID[38505854]
NPT28438 Unchecked Unchecked n.a. Activity n.a. n.a. n.a. PMID[37983270]
NPT2 Others Unspecified n.a. Potency n.a. 60537.8 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. AC50 n.a. 1122.0 nM PubChem BioAssay data set

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT32 Organism Mus musculus Mus musculus ED50 = 0.4 mg.kg-1 PMID[32077284]
NPT32 Organism Mus musculus Mus musculus Activity n.a. n.a. n.a. PMID[37983270]





 Experimental ADME

Experiment Model Experiment Tissue ADME Type ADME Relation ADME Value ADME Unit Reference
Mus musculus n.a. AUC = 397.3 ng.hr.mL-1 PMID[37983270]
Mus musculus n.a. Cmax = 854.88 nM PMID[37983270]
Mus musculus n.a. Drug metabolism = 80.0 % PMID[37983270]
Mus musculus n.a. Cmax = 186.1 nM PMID[37983270]
Mus musculus n.a. Drug metabolism n.a. n.a. n.a. PMID[37983270]
Homo sapiens Intestine T1/2 = 3.25 hr PMID[37983270]
Homo sapiens Intestine Drug metabolism = 0.172 uM PMID[37983270]
Homo sapiens Intestine Drug metabolism = 0.621 uM PMID[37983270]
Homo sapiens Liver Drug metabolism = 0.0 uM PMID[37983270]
Mus musculus n.a. AUC = 84.4 ng.hr.mL-1 PMID[37983270]
Homo sapiens Serum Drug metabolism = 0.0 uM PMID[37983270]





 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 NPC106937 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
0.6545 Remote Similarity NPC610692
0.5273 Remote Similarity NPC13880
0.5185 Remote Similarity NPC73767
0.5172 Remote Similarity NPC92111
0.5088 Remote Similarity NPC600620

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC106937 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
1.0 High Similarity NPD802 Phase 3

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