Natural Product: NPC208972

Natural Product IDNPC208972
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 LACQUZXTVNKQKI-QSXUWXSHSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 44257366
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0000507] Isoflavonoid O-glycosides

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 LACQUZXTVNKQKI-QSXUWXSHSA-N
Standard InCHI InChI=1S/C23H24O12/c1-31-13-5-9(3-4-11(13)25)10-8-33-22-16(17(10)27)12(26)6-14(21(22)32-2)34-23-20(30)19(29)18(28)15(7-24)35-23/h3-6,8,15,18-20,23-26,28-30H,7H2,1-2H3/t15?,18-,19+,20?,23-/m1/s1
SMILES COc1cc(ccc1O)c1coc2c(c(cc(c2OC)O[C@H]2C([C@H]([C@@H](C(CO)O2)O)O)O)O)c1=O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   492.13 Volume:   456.529
?
Van der Waals volume.
Dense:   1.078 LogP:   -0.298
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.942
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.706
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   24.0
TPSA:   188.51
?
Topological Polar Surface Area.
 H-Bond Acceptor:   12.0
H-Bond Donor:   6.0 Rings:   4.0
Heavy Atoms:   12.0

MedChem Properties

QED Drug-Likeness Score:   0.272 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.042 Fsp3:   0.348
MCE-18:   89.71
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Accepted
Pfizer Rule:   Rejected GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.537 Fluc inhibitor:   0.188
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.891
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.862
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.082 Promiscuous compounds:   0.351

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.069 MDCK Permeability:   -5.328
Pgp-inhibitor:   0.0 Pgp-substrate:   0.818
PAMPA:   0.999
?
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):   0.846
20% Bioavailability (F20%):   0.764 30% Bioavailability (F30%):   0.987
50% Bioavailability (F50%):   0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.799
Plasma Protein Binding (PPB):   78.854% Volume Distribution (VD):   -0.047
Fu: 22.061%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.901
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.475
BSEP inhibitor:   0.005

ADMET: Metabolism

CYP1A2-inhibitor:   0.011 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.71 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.078
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.662
HLM stability:   0.001
?
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):  3.045 Half-life (T1/2):  3.477

ADMET: Toxicity

hERG Blockers:  0.063 hERG Blockers (10um):  0.33
Human Hepatotoxicity (H-HT):  0.542 Drug-induced Liver Injury (DILI):  0.83
AMES Toxicity:  0.643 Rat Oral Acute Toxicity:  0.166
Maximum Recommended Daily Dose:  0.165 Skin Sensitization:  0.783
Carcinogencity:  0.307 Eye Corrosion:  0.0
Eye Irritation:  0.09 Respiratory Toxicity:  0.108
Drug-induced Neurotoxicity:  0.028 Ototoxicity:  0.905
Hematotoxicity:  0.173 Drug-induced Nephrotoxicity:  0.447
Genotoxicity:  0.295 RPMI-8226 Immunitoxicity:  0.198
A549 Cytotoxicity:  0.284 Hek293 Cytotoxicity:  0.41
BCF:   0.396
?
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:   2.915
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.326
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.537
?
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
NPO14417 Iris tectorum Species Iridaceae Eukaryota n.a. n.a. n.a. PMID[10075762]
NPO7528 Belamcanda chinensis Species Iridaceae Eukaryota n.a. n.a. n.a. PMID[21465599]
NPO14417 Iris tectorum Species Iridaceae Eukaryota n.a. n.a. n.a. PMID[24433009]
NPO7528 Belamcanda chinensis Species Iridaceae Eukaryota n.a. n.a. n.a. PMID[25036154]
NPO14417 Iris tectorum Species Iridaceae Eukaryota n.a. n.a. n.a. PMID[28032759]
NPO7528 Belamcanda chinensis Species Iridaceae Eukaryota Rhizomes n.a. n.a. PMID[31246464]
NPO14417 Iris tectorum Species Iridaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14417 Iris tectorum Species Iridaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7528 Belamcanda chinensis Species Iridaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14417 Iris tectorum Species Iridaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14417 Iris tectorum Species Iridaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO14417 Iris tectorum Species Iridaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO7528 Belamcanda chinensis Species Iridaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO14417 Iris tectorum Species Iridaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7528 Belamcanda chinensis Species Iridaceae 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 NPC208972 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
0.7439 Intermediate Similarity NPC48773
0.6628 Remote Similarity NPC479407
0.6163 Remote Similarity NPC205076
0.6118 Remote Similarity NPC197896
0.6118 Remote Similarity NPC313163
0.6092 Remote Similarity NPC481043
0.6047 Remote Similarity NPC73511
0.5955 Remote Similarity NPC307518
0.593 Remote Similarity NPC105511
0.5909 Remote Similarity NPC224462
0.5765 Remote Similarity NPC93099
0.5568 Remote Similarity NPC156457
0.5568 Remote Similarity NPC603782
0.5444 Remote Similarity NPC100720
0.5435 Remote Similarity NPC311830
0.5393 Remote Similarity NPC234739
0.5385 Remote Similarity NPC80140
0.5376 Remote Similarity NPC601586
0.5341 Remote Similarity NPC135345
0.5326 Remote Similarity NPC229729
0.5281 Remote Similarity NPC210042
0.5275 Remote Similarity NPC138540
0.5269 Remote Similarity NPC602805
0.5258 Remote Similarity NPC479405
0.5222 Remote Similarity NPC258035
0.5222 Remote Similarity NPC161749
0.5213 Remote Similarity NPC203050
0.5213 Remote Similarity NPC488072
0.5213 Remote Similarity NPC225434
0.5204 Remote Similarity NPC479404
0.5185 Remote Similarity NPC473045
0.5185 Remote Similarity NPC114192
0.5161 Remote Similarity NPC101026
0.5161 Remote Similarity NPC488077
0.5111 Remote Similarity NPC44558
0.5111 Remote Similarity NPC348541
0.5106 Remote Similarity NPC607201
0.5054 Remote Similarity NPC479401
0.5053 Remote Similarity NPC469931

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC208972 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
0.5222 Remote Similarity NPD4381 Clinical (unspecified phase)

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