Natural Product: NPC485986

Natural Product IDNPC485986
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 WMZPWUBGSYJEET-HOTGVXAUSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 101705172
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002650] Diarylheptanoids
        • [CHEMONTID:0002652] Cyclic diarylheptanoids
          • [CHEMONTID:0003523] Meta,para-diphenylether diarylheptanoids

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 WMZPWUBGSYJEET-HOTGVXAUSA-N
Standard InCHI InChI=1S/C19H22O4/c20-15-6-1-13-3-8-17(9-4-13)23-19-11-14(5-10-18(19)22)2-7-16(21)12-15/h3-5,8-11,15-16,20-22H,1-2,6-7,12H2/t15-,16-/m0/s1
SMILES C1C[C@@H](C[C@H](CCc2ccc(c(c2)Oc2ccc1cc2)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   314.15 Volume:   330.853
?
Van der Waals volume.
Dense:   0.95 LogP:   2.546
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.512
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.598
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   22.0
TPSA:   69.92
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   3.0 Rings:   4.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.698 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.049 Fsp3:   0.368
MCE-18:   56.615
?
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:   0.495 Fluc inhibitor:   0.89
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.074
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.097
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.391 Promiscuous compounds:   0.281

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.136 MDCK Permeability:   -4.933
Pgp-inhibitor:   0.072 Pgp-substrate:   0.927
PAMPA:   0.691
?
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):   0.002
20% Bioavailability (F20%):   0.468 30% Bioavailability (F30%):   0.682
50% Bioavailability (F50%):   0.936

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.035 MRP1:   0.691
Plasma Protein Binding (PPB):   96.281% Volume Distribution (VD):   -0.165
Fu: 3.543%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.785
OATP1B3 inhibitor:   0.765 BCRP inhibitor:   0.199
BSEP inhibitor:   0.869

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.014 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.006 CYP3A4-substrate:   0.057
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.287
HLM stability:   0.045
?
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):  11.455 Half-life (T1/2):  1.853

ADMET: Toxicity

hERG Blockers:  0.134 hERG Blockers (10um):  0.347
Human Hepatotoxicity (H-HT):  0.409 Drug-induced Liver Injury (DILI):  0.073
AMES Toxicity:  0.557 Rat Oral Acute Toxicity:  0.17
Maximum Recommended Daily Dose:  0.644 Skin Sensitization:  0.969
Carcinogencity:  0.675 Eye Corrosion:  0.057
Eye Irritation:  0.978 Respiratory Toxicity:  0.555
Drug-induced Neurotoxicity:  0.085 Ototoxicity:  0.413
Hematotoxicity:  0.093 Drug-induced Nephrotoxicity:  0.312
Genotoxicity:  0.015 RPMI-8226 Immunitoxicity:  0.062
A549 Cytotoxicity:  0.84 Hek293 Cytotoxicity:  0.486
BCF:   0.325
?
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:   2.768
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.335
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.375
?
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
NPO13332 Tacca chantrieri Species Taccaceae Eukaryota rhizomes SiMao City, Yunnan Province, China 1996-OCT PMID[11908966]
NPO13332 Tacca chantrieri Species Taccaceae Eukaryota Rhizomes n.a. n.a. PMID[12350150]
NPO13332 Tacca chantrieri Species Taccaceae Eukaryota n.a. n.a. n.a. PMID[20715765]
NPO13332 Tacca chantrieri Species Taccaceae Eukaryota n.a. n.a. n.a. PMID[33253561]
NPO13332 Tacca chantrieri Species Taccaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13332 Tacca chantrieri Species Taccaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO13332 Tacca chantrieri Species Taccaceae 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
NPT34 Cell line BV-2 Mus musculus Activity = 84.6 % PMID[33253561]
NPT34 Cell line BV-2 Mus musculus Activity = 98.8 % PMID[33253561]

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 NPC485986 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
0.78 Intermediate Similarity NPC127389
0.78 Intermediate Similarity NPC290451
0.78 Intermediate Similarity NPC17109
0.625 Remote Similarity NPC312675
0.625 Remote Similarity NPC262156
0.625 Remote Similarity NPC184651
0.625 Remote Similarity NPC113865
0.617 Remote Similarity NPC86947
0.6078 Remote Similarity NPC473853
0.6078 Remote Similarity NPC470212
0.6 Remote Similarity NPC3221
0.5962 Remote Similarity NPC324571
0.5789 Remote Similarity NPC280391
0.5789 Remote Similarity NPC241354
0.5769 Remote Similarity NPC98631
0.5769 Remote Similarity NPC206615
0.5556 Remote Similarity NPC343720
0.5556 Remote Similarity NPC54872
0.537 Remote Similarity NPC5948
0.5357 Remote Similarity NPC311595
0.5357 Remote Similarity NPC24474
0.5333 Remote Similarity NPC91461
0.5333 Remote Similarity NPC7686
0.5333 Remote Similarity NPC40258
0.5319 Remote Similarity NPC474272
0.5306 Remote Similarity NPC474320
0.5294 Remote Similarity NPC474214
0.5283 Remote Similarity NPC186843
0.5088 Remote Similarity NPC599909
0.5088 Remote Similarity NPC604545

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC485986 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