Natural Product: NPC481088

Natural Product IDNPC481088
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 GKWYIORVUKKSLZ-GMVOTWDCSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]

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 GKWYIORVUKKSLZ-GMVOTWDCSA-N
Standard InCHI InChI=1S/C20H22O8/c1-26-16-7-11(3-5-14(16)22)9-20(25)13(10-21)18(28-19(20)24)12-4-6-15(23)17(8-12)27-2/h3-8,13,18,21-23,25H,9-10H2,1-2H3/t13-,18-,20-/m0/s1
SMILES COc1cc(ccc1O)C[C@@]1([C@@H](CO)[C@H](c2ccc(c(c2)OC)O)OC1=O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   390.13 Volume:   380.673
?
Van der Waals volume.
Dense:   1.025 LogP:   0.708
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.189
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.494
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   18.0
TPSA:   125.68
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   4.0 Rings:   3.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.544 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.726 Fsp3:   0.35
MCE-18:   67.667
?
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:   0.158 Fluc inhibitor:   0.421
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.013
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.287
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.234 Promiscuous compounds:   0.171

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.339 MDCK Permeability:   -4.908
Pgp-inhibitor:   0.044 Pgp-substrate:   0.641
PAMPA:   0.247
?
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):   0.004
20% Bioavailability (F20%):   0.139 30% Bioavailability (F30%):   0.4
50% Bioavailability (F50%):   0.994

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.892
Plasma Protein Binding (PPB):   81.254% Volume Distribution (VD):   -0.054
Fu: 22.555%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.485
BSEP inhibitor:   0.845

ADMET: Metabolism

CYP1A2-inhibitor:   0.926 CYP1A2-substrate:   0.151
CYP2C19-inhibitor:   0.847 CYP2C19-substrate:   0.007
CYP2C9-inhibitor:   0.962 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.023 CYP2D6-substrate:   0.657
CYP3A4-inhibitor:   0.991 CYP3A4-substrate:   0.002
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.787
HLM stability:   0.979
?
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):  6.396 Half-life (T1/2):  2.924

ADMET: Toxicity

hERG Blockers:  0.029 hERG Blockers (10um):  0.253
Human Hepatotoxicity (H-HT):  0.504 Drug-induced Liver Injury (DILI):  0.556
AMES Toxicity:  0.489 Rat Oral Acute Toxicity:  0.048
Maximum Recommended Daily Dose:  0.251 Skin Sensitization:  0.935
Carcinogencity:  0.372 Eye Corrosion:  0.006
Eye Irritation:  0.934 Respiratory Toxicity:  0.075
Drug-induced Neurotoxicity:  0.068 Ototoxicity:  0.523
Hematotoxicity:  0.189 Drug-induced Nephrotoxicity:  0.332
Genotoxicity:  0.646 RPMI-8226 Immunitoxicity:  0.072
A549 Cytotoxicity:  0.098 Hek293 Cytotoxicity:  0.234
BCF:   0.6
?
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:   3.209
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.369
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.732
?
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
NPO18950 Cephalotaxus fortunei Species Taxaceae Eukaryota n.a. n.a. n.a. PMID[12542368]
NPO18950 Cephalotaxus fortunei Species Taxaceae Eukaryota n.a. n.a. n.a. PMID[28139925]
NPO18950 Cephalotaxus fortunei Species Taxaceae Eukaryota n.a. n.a. n.a. PMID[31184894]
NPO18950 Cephalotaxus fortunei Species Taxaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18950 Cephalotaxus fortunei Species Taxaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18950 Cephalotaxus fortunei Species Taxaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18950 Cephalotaxus fortunei Species Taxaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO18950 Cephalotaxus fortunei Species Taxaceae 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
NPT116 Cell line HL-60 Homo sapiens GI < 50.0 % PMID[28139925]
NPT81 Cell line A549 Homo sapiens GI < 50.0 % PMID[28139925]

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 NPC481088 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
0.661 Remote Similarity NPC277804
0.6491 Remote Similarity NPC481089
0.6333 Remote Similarity NPC610652
0.6296 Remote Similarity NPC147379
0.5846 Remote Similarity NPC471988
0.5833 Remote Similarity NPC253481
0.5833 Remote Similarity NPC253722
0.5741 Remote Similarity NPC242807
0.5741 Remote Similarity NPC153739
0.5645 Remote Similarity NPC187998
0.5645 Remote Similarity NPC257582
0.5645 Remote Similarity NPC241522
0.5345 Remote Similarity NPC5428
0.5303 Remote Similarity NPC31751
0.5231 Remote Similarity NPC282833
0.5185 Remote Similarity NPC85488
0.5179 Remote Similarity NPC142985
0.5152 Remote Similarity NPC67247
0.5091 Remote Similarity NPC282703
0.5091 Remote Similarity NPC184733
0.5091 Remote Similarity NPC128208
0.5091 Remote Similarity NPC129570
0.5091 Remote Similarity NPC63238
0.5091 Remote Similarity NPC602603
0.5082 Remote Similarity NPC478955
0.5082 Remote Similarity NPC478700
0.5077 Remote Similarity NPC23646
0.5077 Remote Similarity NPC485397
0.5075 Remote Similarity NPC42300

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC481088 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