Natural Product: NPC3960

Natural Product IDNPC3960
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 FMZOHNLGBVZQAC-AWEZNQCLSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 101648678
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0004150] Hydrocarbon derivatives
      • [CHEMONTID:0001650] Tropones

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 FMZOHNLGBVZQAC-AWEZNQCLSA-N
Standard InCHI InChI=1S/C20H21NO6/c1-25-16-7-5-12-13(9-15(16)23)14(21-10-22)6-4-11-8-17(26-2)19(24)20(27-3)18(11)12/h5,7-10,14,24H,4,6H2,1-3H3,(H,21,22)/t14-/m0/s1
SMILES COc1ccc2-c3c(CC[C@@H](c2cc1=O)N=CO)cc(c(c3OC)O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   371.14 Volume:   371.453
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Van der Waals volume.
Dense:   0.999 LogP:   1.335
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.735
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.165
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The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   20.0
TPSA:   97.58
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.633 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.507 Fsp3:   0.3
MCE-18:   61.385
?
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:   0.32 Fluc inhibitor:   0.356
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.492
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.516
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.007 Promiscuous compounds:   0.128

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.09 MDCK Permeability:   -4.753
Pgp-inhibitor:   0.077 Pgp-substrate:   0.559
PAMPA:   0.711
?
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):   0.419
20% Bioavailability (F20%):   0.299 30% Bioavailability (F30%):   0.386
50% Bioavailability (F50%):   0.981

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.868
Plasma Protein Binding (PPB):   92.771% Volume Distribution (VD):   -0.486
Fu: 6.442%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.975
OATP1B3 inhibitor:   0.985 BCRP inhibitor:   0.561
BSEP inhibitor:   0.652

ADMET: Metabolism

CYP1A2-inhibitor:   0.592 CYP1A2-substrate:   0.184
CYP2C19-inhibitor:   0.64 CYP2C19-substrate:   0.267
CYP2C9-inhibitor:   0.501 CYP2C9-substrate:   0.003
CYP2D6-inhibitor:   0.651 CYP2D6-substrate:   0.005
CYP3A4-inhibitor:   0.996 CYP3A4-substrate:   0.067
CYP2B6-substrate:   0.033 CYP2C8-inhibitor:   0.908
HLM stability:   0.26
?
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):  1.523 Half-life (T1/2):  1.988

ADMET: Toxicity

hERG Blockers:  0.06 hERG Blockers (10um):  0.174
Human Hepatotoxicity (H-HT):  0.857 Drug-induced Liver Injury (DILI):  0.58
AMES Toxicity:  0.843 Rat Oral Acute Toxicity:  0.666
Maximum Recommended Daily Dose:  0.95 Skin Sensitization:  0.915
Carcinogencity:  0.859 Eye Corrosion:  0.0
Eye Irritation:  0.086 Respiratory Toxicity:  0.928
Drug-induced Neurotoxicity:  0.799 Ototoxicity:  0.541
Hematotoxicity:  0.776 Drug-induced Nephrotoxicity:  0.915
Genotoxicity:  1.0 RPMI-8226 Immunitoxicity:  0.25
A549 Cytotoxicity:  0.108 Hek293 Cytotoxicity:  0.684
BCF:   0.792
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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:   3.5
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.897
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.21
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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
NPO4250 Gloriosa superba Species Colchicaceae Eukaryota n.a. n.a. n.a. DOI[10.1007/s10529-006-0004-9]
NPO22241 Alangium villosum Species Cornaceae Eukaryota stem bark Ceram, Indonesia 1998 PMID[18327911]
NPO22241 Alangium villosum Species Cornaceae Eukaryota n.a. n.a. n.a. PMID[32372642]
NPO4250 Gloriosa superba Species Colchicaceae Eukaryota n.a. n.a. n.a. PMID[32372642]
NPO4250 Gloriosa superba Species Colchicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22241 Alangium villosum Species Cornaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4250 Gloriosa superba Species Colchicaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO4250 Gloriosa superba Species Colchicaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO4250 Gloriosa superba Species Colchicaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22241 Alangium villosum Species Cornaceae 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 NPC3960 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
0.8197 Intermediate Similarity NPC202839
0.7143 Intermediate Similarity NPC44642
0.5942 Remote Similarity NPC66678
0.5797 Remote Similarity NPC108957
0.5797 Remote Similarity NPC14005
0.5797 Remote Similarity NPC226941
0.5735 Remote Similarity NPC188120
0.5333 Remote Similarity NPC189782

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC3960 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
0.5797 Remote Similarity NPD5089 Approved
0.5797 Remote Similarity NPD5090 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