Natural Product: NPC32614

Natural Product IDNPC32614
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 JKCVMTYNARDGET-IYBDPMFKSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 11428305
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds
      • [CHEMONTID:0001969] Dibenzylbutane lignans
        • [CHEMONTID:0001624] Dibenzylbutanediol lignans

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 JKCVMTYNARDGET-IYBDPMFKSA-N
Standard InCHI InChI=1S/C20H22O6/c21-9-15(5-13-1-3-17-19(7-13)25-11-23-17)16(10-22)6-14-2-4-18-20(8-14)26-12-24-18/h1-4,7-8,15-16,21-22H,5-6,9-12H2/t15-,16+
SMILES c1cc2c(cc1C[C@@H](CO)[C@H](Cc1ccc3c(c1)OCO3)CO)OCO2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   358.14 Volume:   357.173
?
Van der Waals volume.
Dense:   1.003 LogP:   2.03
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.267
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.513
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   20.0
TPSA:   77.38
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.79 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.215 Fsp3:   0.4
MCE-18:   62.857
?
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:   0.411 Fluc inhibitor:   0.413
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.017
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.148
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.283 Promiscuous compounds:   0.215

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.042 MDCK Permeability:   -4.825
Pgp-inhibitor:   0.731 Pgp-substrate:   0.006
PAMPA:   0.33
?
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):   0.0
20% Bioavailability (F20%):   0.048 30% Bioavailability (F30%):   0.0
50% Bioavailability (F50%):   0.359

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.925 MRP1:   0.178
Plasma Protein Binding (PPB):   86.201% Volume Distribution (VD):   0.001
Fu: 15.252%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.965
OATP1B3 inhibitor:   0.82 BCRP inhibitor:   0.006
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.998 CYP1A2-substrate:   0.97
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.988
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   1.0
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   0.463 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.22 CYP2C8-inhibitor:   0.0
HLM stability:   0.891
?
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):  4.835 Half-life (T1/2):  1.008

ADMET: Toxicity

hERG Blockers:  0.133 hERG Blockers (10um):  0.259
Human Hepatotoxicity (H-HT):  0.837 Drug-induced Liver Injury (DILI):  0.727
AMES Toxicity:  0.738 Rat Oral Acute Toxicity:  0.046
Maximum Recommended Daily Dose:  0.035 Skin Sensitization:  0.979
Carcinogencity:  0.662 Eye Corrosion:  0.003
Eye Irritation:  0.794 Respiratory Toxicity:  0.052
Drug-induced Neurotoxicity:  0.52 Ototoxicity:  0.865
Hematotoxicity:  0.412 Drug-induced Nephrotoxicity:  0.825
Genotoxicity:  0.753 RPMI-8226 Immunitoxicity:  0.078
A549 Cytotoxicity:  0.1 Hek293 Cytotoxicity:  0.183
BCF:   1.484
?
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:   3.627
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.497
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.383
?
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
NPO1768 Sansevieria ehrenbergii Species Asparagaceae Eukaryota n.a. African n.a. PMID[15921418]
NPO8160 Diospyros montana Species Ebenaceae Eukaryota n.a. n.a. n.a. PMID[17400463]
NPO11451 Lespedeza cyrtobotrya Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[19102656]
NPO17154 Hymenaea oblongifolia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14332 Uvaria ferruginea Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1768 Sansevieria ehrenbergii Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9374 Veronica anagallis-aquatica Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8160 Diospyros montana Species Ebenaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17618 Flaveria bidentis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11451 Lespedeza cyrtobotrya Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11451 Lespedeza cyrtobotrya Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11451 Lespedeza cyrtobotrya Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17618 Flaveria bidentis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14611 Teucrium fragile Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2535 Bunodactis xanthogrammica Species Actiniidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11451 Lespedeza cyrtobotrya Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14332 Uvaria ferruginea Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22851 Kryptoperidinium foliaceum Species Peridiniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9374 Veronica anagallis-aquatica Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17009 Ptelea crenulata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17154 Hymenaea oblongifolia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO668 Cnidoscolus texanus Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1768 Sansevieria ehrenbergii Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12642 Podadenia thwaitesii n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO16062 Trichilia dregeana Species Meliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8160 Diospyros montana Species Ebenaceae 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 NPC32614 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
1.0 High Similarity NPC40352
1.0 High Similarity NPC213711
0.8462 Intermediate Similarity NPC196937
0.7143 Intermediate Similarity NPC606623
0.7027 Intermediate Similarity NPC80241
0.7027 Intermediate Similarity NPC301641
0.7027 Intermediate Similarity NPC485483
0.64 Remote Similarity NPC487677
0.64 Remote Similarity NPC487675
0.6341 Remote Similarity NPC150534
0.6341 Remote Similarity NPC344161
0.619 Remote Similarity NPC600801
0.6087 Remote Similarity NPC104077
0.6087 Remote Similarity NPC219671
0.6087 Remote Similarity NPC147616
0.6053 Remote Similarity NPC31279
0.6 Remote Similarity NPC249788
0.5957 Remote Similarity NPC171550
0.5957 Remote Similarity NPC134764
0.5909 Remote Similarity NPC476748
0.5882 Remote Similarity NPC47181
0.5769 Remote Similarity NPC601256
0.5745 Remote Similarity NPC485480
0.5652 Remote Similarity NPC485482
0.5532 Remote Similarity NPC607444
0.5517 Remote Similarity NPC156376
0.551 Remote Similarity NPC274356
0.551 Remote Similarity NPC101748
0.5476 Remote Similarity NPC604144
0.5417 Remote Similarity NPC192255
0.5417 Remote Similarity NPC110958
0.5417 Remote Similarity NPC474288
0.5417 Remote Similarity NPC19890
0.5385 Remote Similarity NPC18576
0.5294 Remote Similarity NPC28398
0.5283 Remote Similarity NPC185908
0.5283 Remote Similarity NPC482891
0.5208 Remote Similarity NPC487685
0.52 Remote Similarity NPC158737
0.52 Remote Similarity NPC143895
0.5185 Remote Similarity NPC3982
0.5116 Remote Similarity NPC259742
0.5098 Remote Similarity NPC165128

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC32614 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
0.5349 Remote Similarity NPD554 Phase 3

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