Natural Product: NPC293707

Natural Product IDNPC293707
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 QOXQVMHGUNMPOZ-RIJSRGPQSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 46873057
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000264] Organic acids and derivatives
      • [CHEMONTID:0000265] Carboxylic acids and derivatives
        • [CHEMONTID:0000013] Amino acids, peptides, and analogues
          • [CHEMONTID:0000347] Amino acids and derivatives
            • [CHEMONTID:0000060] Alpha amino acids 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 QOXQVMHGUNMPOZ-RIJSRGPQSA-N
Standard InCHI InChI=1S/C20H24N2O6S2/c1-29-19-7-9-11(23)3-5-13(25)15(9)21(19)18(28)20(30-2)8-10-12(24)4-6-14(26)16(10)22(20)17(19)27/h3,5,9-10,13-16,25-26H,4,6-8H2,1-2H3/t9-,10-,13-,14-,15-,16-,19+,20+/m0/s1
SMILES CS[C@]12C[C@H]3C(=O)C=C[C@@H]([C@H]3N2C(=O)[C@@]2(C[C@H]3C(=O)CC[C@@H]([C@H]3N2C1=O)O)SC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   452.11 Volume:   410.265
?
Van der Waals volume.
Dense:   1.102 LogP:   0.008
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.68
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.43
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   28.0
TPSA:   115.22
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   2.0 Rings:   5.0
Heavy Atoms:   10.0

MedChem Properties

QED Drug-Likeness Score:   0.591 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.547 Fsp3:   0.7
MCE-18:   89.294
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.739 Fluc inhibitor:   0.001
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.184
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.042
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.637 Promiscuous compounds:   0.02

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.446 MDCK Permeability:   -5.185
Pgp-inhibitor:   0.067 Pgp-substrate:   0.707
PAMPA:   0.983
?
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):   0.188
20% Bioavailability (F20%):   0.075 30% Bioavailability (F30%):   0.165
50% Bioavailability (F50%):   0.623

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.006 MRP1:   0.627
Plasma Protein Binding (PPB):   56.288% Volume Distribution (VD):   0.031
Fu: 44.871%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.397
OATP1B3 inhibitor:   0.576 BCRP inhibitor:   0.001
BSEP inhibitor:   0.747

ADMET: Metabolism

CYP1A2-inhibitor:   0.434 CYP1A2-substrate:   0.043
CYP2C19-inhibitor:   0.558 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.002 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.03
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.428
HLM stability:   0.983
?
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):  5.394 Half-life (T1/2):  2.262

ADMET: Toxicity

hERG Blockers:  0.017 hERG Blockers (10um):  0.09
Human Hepatotoxicity (H-HT):  0.937 Drug-induced Liver Injury (DILI):  0.959
AMES Toxicity:  0.515 Rat Oral Acute Toxicity:  0.313
Maximum Recommended Daily Dose:  0.1 Skin Sensitization:  1.0
Carcinogencity:  0.913 Eye Corrosion:  0.0
Eye Irritation:  0.233 Respiratory Toxicity:  0.132
Drug-induced Neurotoxicity:  0.023 Ototoxicity:  0.297
Hematotoxicity:  0.848 Drug-induced Nephrotoxicity:  0.974
Genotoxicity:  1.0 RPMI-8226 Immunitoxicity:  0.137
A549 Cytotoxicity:  0.065 Hek293 Cytotoxicity:  0.428
BCF:   0.62
?
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:   3.369
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.078
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.491
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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
NPO18557 Epicoccum nigrum Species Didymellaceae Eukaryota n.a. n.a. n.a. PMID[17711348]
NPO18557 Epicoccum nigrum Species Didymellaceae Eukaryota n.a. n.a. n.a. PMID[19919067]
NPO18557 Epicoccum nigrum Species Didymellaceae Eukaryota n.a. The fungus is isolated from the leaves of L. rhodostegia, collected in June 2007 at Nanning, Guangxi Province, China 2007-JUN PMID[20550196]
NPO28219 Euphorbia peplus Species Euphorbiaceae Eukaryota n.a. n.a. n.a. PMID[21612217]
NPO18557 Epicoccum nigrum Species Didymellaceae Eukaryota n.a. n.a. n.a. PMID[24328302]
NPO28219 Euphorbia peplus Species Euphorbiaceae Eukaryota n.a. n.a. n.a. PMID[27203291]
NPO28310 Phacelocarpus labillardieri Species Phacelocarpaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28219 Euphorbia peplus Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18557 Epicoccum nigrum Species Didymellaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18557 Epicoccum nigrum Species Didymellaceae Eukaryota n.a. n.a. n.a. Database[Title]
NPO28310 Phacelocarpus labillardieri Species Phacelocarpaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28982 Calliandra confusa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28129 Reticulitermes virginicus Species Termitoidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27974 Swertia leduci Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23882 Cremastosperma microcarpum Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28114 Peltophorum adnatum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18557 Epicoccum nigrum Species Didymellaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28219 Euphorbia peplus Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23676 Fleroya rubrostipulata Species Rubiaceae 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 NPC293707 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
0.7907 Intermediate Similarity NPC41162
0.7442 Intermediate Similarity NPC28542
0.6863 Remote Similarity NPC485901
0.5806 Remote Similarity NPC483103
0.5161 Remote Similarity NPC211848
0.5098 Remote Similarity NPC262880
0.5098 Remote Similarity NPC247902

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC293707 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
NPD

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