Natural Product: NPC313654

Natural Product IDNPC313654
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 XSQDFRPRMRYUHM-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 4210613
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000279] Alkaloids and derivatives
      • [CHEMONTID:0002679] Ergoline and derivatives
        • [CHEMONTID:0002680] Lysergic acids and derivatives
          • [CHEMONTID:0002746] Lysergamides

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 XSQDFRPRMRYUHM-UHFFFAOYSA-N
Standard InCHI InChI=1S/C19H23N3O/c1-11(2)21-19(23)13-7-15-14-5-4-6-16-18(14)12(9-20-16)8-17(15)22(3)10-13/h4-7,9,11,13,17,20H,8,10H2,1-3H3,(H,21,23)
SMILES CC(C)NC(=O)C1CN(C2CC3=CNC4=CC=CC(=C34)C2=C1)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   309.18 Volume:   328.916
?
Van der Waals volume.
Dense:   0.94 LogP:   2.454
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.522
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.898
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The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   20.0
TPSA:   48.13
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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:   0.896 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.536 Fsp3:   0.421
MCE-18:   72.519
?
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:   0.171 Fluc inhibitor:   0.318
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.802
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.718
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.003 Promiscuous compounds:   0.221

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.267 MDCK Permeability:   -4.861
Pgp-inhibitor:   0.099 Pgp-substrate:   0.736
PAMPA:   0.053
?
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):   0.007
20% Bioavailability (F20%):   0.019 30% Bioavailability (F30%):   0.054
50% Bioavailability (F50%):   0.422

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.94 MRP1:   0.891
Plasma Protein Binding (PPB):   52.583% Volume Distribution (VD):   -0.038
Fu: 47.756%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.355
OATP1B3 inhibitor:   0.654 BCRP inhibitor:   0.133
BSEP inhibitor:   0.881

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.013 CYP2C9-substrate:   1.0
CYP2D6-inhibitor:   0.966 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.132 CYP2C8-inhibitor:   0.0
HLM stability:   0.964
?
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):  14.553 Half-life (T1/2):  3.349

ADMET: Toxicity

hERG Blockers:  0.267 hERG Blockers (10um):  0.503
Human Hepatotoxicity (H-HT):  0.43 Drug-induced Liver Injury (DILI):  0.044
AMES Toxicity:  0.456 Rat Oral Acute Toxicity:  0.597
Maximum Recommended Daily Dose:  0.717 Skin Sensitization:  0.118
Carcinogencity:  0.484 Eye Corrosion:  0.0
Eye Irritation:  0.015 Respiratory Toxicity:  0.878
Drug-induced Neurotoxicity:  0.719 Ototoxicity:  0.897
Hematotoxicity:  0.127 Drug-induced Nephrotoxicity:  0.051
Genotoxicity:  0.986 RPMI-8226 Immunitoxicity:  0.03
A549 Cytotoxicity:  0.019 Hek293 Cytotoxicity:  0.287
BCF:   0.566
?
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:   3.363
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.978
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.376
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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
NPO24009 Claviceps purpurea Species Clavicipitaceae Eukaryota n.a. n.a. n.a. PMID[17841110]
NPO24009 Claviceps purpurea Species Clavicipitaceae Eukaryota n.a. n.a. n.a. PMID[20778930]
NPO24009 Claviceps purpurea Species Clavicipitaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2695 Ipomoea argyrophylla Species Convolvulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24009 Claviceps purpurea Species Clavicipitaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2695 Ipomoea argyrophylla Species Convolvulaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24009 Claviceps purpurea Species Clavicipitaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2695 Ipomoea argyrophylla Species Convolvulaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24009 Claviceps purpurea Species Clavicipitaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO2695 Ipomoea argyrophylla Species Convolvulaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO24009 Claviceps purpurea Species Clavicipitaceae 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 NPC313654 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
0.8769 High Similarity NPC604662
0.8507 High Similarity NPC611966
0.7258 Intermediate Similarity NPC606264
0.7042 Intermediate Similarity NPC68354
0.6716 Remote Similarity NPC194411
0.6667 Remote Similarity NPC275305
0.6667 Remote Similarity NPC37423
0.6 Remote Similarity NPC603739
0.5735 Remote Similarity NPC600946
0.5426 Remote Similarity NPC155444
0.5152 Remote Similarity NPC56109
0.5152 Remote Similarity NPC191382

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC313654 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
0.7042 Intermediate Similarity NPD3506 Phase 4
0.6912 Remote Similarity NPD4075 Phase 2
0.6849 Remote Similarity NPD4079 Phase 4
0.6494 Remote Similarity NPD3505 Approved
0.6329 Remote Similarity NPD4076 Approved
0.6316 Remote Similarity NPD3961 Phase 2
0.5513 Remote Similarity NPD4128 Phase 4
0.5152 Remote Similarity NPD7781 Phase 4

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