Natural Product: NPC145144

Natural Product IDNPC145144
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 YCVHVPIQJHDUCW-ZXJYCPGTSA-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]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds
      • [CHEMONTID:0003686] Furanoid lignans
        • [CHEMONTID:0001604] Tetrahydrofuran lignans
          • [CHEMONTID:0003424] 9,9'-epoxylignans

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 YCVHVPIQJHDUCW-ZXJYCPGTSA-N
Standard InCHI InChI=1S/C22H28O7/c1-25-19-10-13(5-7-17(19)23)9-15-16(12-29-22(15)28-4)21(27-3)14-6-8-18(24)20(11-14)26-2/h5-8,10-11,15-16,21-24H,9,12H2,1-4H3/t15-,16+,21-,22+/m1/s1
SMILES COc1cc(ccc1O)C[C@@H]1[C@H](CO[C@@H]1OC)[C@@H](c1ccc(c(c1)OC)O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   404.18 Volume:   409.112
?
Van der Waals volume.
Dense:   0.988 LogP:   1.354
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.689
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.908
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   8.0 Rigid Bonds:   17.0
TPSA:   86.61
?
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:   0.698 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.859 Fsp3:   0.455
MCE-18:   61.75
?
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:   1 PAINS Alert:   0
Colloidal aggregators:   0.21 Fluc inhibitor:   0.317
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.02
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.201
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.288 Promiscuous compounds:   0.24

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.231 MDCK Permeability:   -4.926
Pgp-inhibitor:   0.214 Pgp-substrate:   0.596
PAMPA:   0.041
?
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%):   0.31 30% Bioavailability (F30%):   0.233
50% Bioavailability (F50%):   0.924

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.902
Plasma Protein Binding (PPB):   87.414% Volume Distribution (VD):   -0.222
Fu: 13.963%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.22
BSEP inhibitor:   0.847

ADMET: Metabolism

CYP1A2-inhibitor:   0.779 CYP1A2-substrate:   0.137
CYP2C19-inhibitor:   0.999 CYP2C19-substrate:   0.3
CYP2C9-inhibitor:   0.999 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.79
CYP3A4-inhibitor:   0.957 CYP3A4-substrate:   0.839
CYP2B6-substrate:   0.132 CYP2C8-inhibitor:   0.322
HLM stability:   0.278
?
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):  10.378 Half-life (T1/2):  1.891

ADMET: Toxicity

hERG Blockers:  0.143 hERG Blockers (10um):  0.565
Human Hepatotoxicity (H-HT):  0.786 Drug-induced Liver Injury (DILI):  0.88
AMES Toxicity:  0.823 Rat Oral Acute Toxicity:  0.379
Maximum Recommended Daily Dose:  0.537 Skin Sensitization:  0.941
Carcinogencity:  0.149 Eye Corrosion:  0.011
Eye Irritation:  0.987 Respiratory Toxicity:  0.669
Drug-induced Neurotoxicity:  0.531 Ototoxicity:  0.511
Hematotoxicity:  0.393 Drug-induced Nephrotoxicity:  0.758
Genotoxicity:  0.914 RPMI-8226 Immunitoxicity:  0.285
A549 Cytotoxicity:  0.347 Hek293 Cytotoxicity:  0.462
BCF:   0.865
?
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:   3.414
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.594
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.974
?
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
NPO23720 Taxus wallichiana Species Taxaceae Eukaryota needles Himalayan n.a. PMID[16480866]
NPO23720 Taxus wallichiana Species Taxaceae Eukaryota Stem Bark n.a. n.a. PMID[28240909]
NPO23720 Taxus wallichiana Species Taxaceae Eukaryota Roots n.a. n.a. PMID[28581744]
NPO23720 Taxus wallichiana Species Taxaceae Eukaryota n.a. n.a. n.a. PMID[7264680]
NPO23720 Taxus wallichiana Species Taxaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23720 Taxus wallichiana Species Taxaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO23720 Taxus wallichiana Species Taxaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23720 Taxus wallichiana Species Taxaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO23720 Taxus wallichiana 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
NPT2 Others Unspecified n.a. IC50 = 133000.0 nM PMID[28581744]

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 NPC145144 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
0.6129 Remote Similarity NPC101624
0.6129 Remote Similarity NPC184938
0.6102 Remote Similarity NPC275950
0.6032 Remote Similarity NPC67247
0.5873 Remote Similarity NPC476345
0.5806 Remote Similarity NPC187998
0.5806 Remote Similarity NPC257582
0.5806 Remote Similarity NPC241522
0.5636 Remote Similarity NPC115207
0.5636 Remote Similarity NPC31344
0.5636 Remote Similarity NPC158079
0.5636 Remote Similarity NPC317769
0.5636 Remote Similarity NPC228346
0.5636 Remote Similarity NPC40432
0.5636 Remote Similarity NPC161557
0.5588 Remote Similarity NPC281780
0.55 Remote Similarity NPC478955
0.55 Remote Similarity NPC478700
0.5469 Remote Similarity NPC610652
0.5417 Remote Similarity NPC67467
0.5405 Remote Similarity NPC472711
0.5362 Remote Similarity NPC267091
0.5254 Remote Similarity NPC126409
0.5254 Remote Similarity NPC99572
0.5246 Remote Similarity NPC27843
0.5246 Remote Similarity NPC7171
0.5231 Remote Similarity NPC110699
0.5231 Remote Similarity NPC23646
0.5231 Remote Similarity NPC106055
0.5231 Remote Similarity NPC485397
0.5224 Remote Similarity NPC42300
0.5152 Remote Similarity NPC486558
0.5152 Remote Similarity NPC282833
0.5147 Remote Similarity NPC64201
0.5088 Remote Similarity NPC142985
0.5079 Remote Similarity NPC223185
0.5079 Remote Similarity NPC610778
0.5075 Remote Similarity NPC485282
0.5075 Remote Similarity NPC485283
0.5075 Remote Similarity NPC485281
0.5072 Remote Similarity NPC471988

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC145144 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