Natural Product: NPC105178

Natural Product IDNPC105178
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 AMVHSCBIZLVSPF-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 5319490
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 AMVHSCBIZLVSPF-UHFFFAOYSA-N
Standard InCHI InChI=1S/C21H28O7/c1-26-18-8-13(4-5-17(18)24)6-15(11-22)16(12-23)7-14-9-19(27-2)21(25)20(10-14)28-3/h4-5,8-10,15-16,22-25H,6-7,11-12H2,1-3H3
SMILES COc1cc(ccc1O)CC(CO)C(Cc1cc(c(c(c1)OC)O)OC)CO

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   392.18 Volume:   400.372
?
Van der Waals volume.
Dense:   0.98 LogP:   1.391
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.809
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.724
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   10.0 Rigid Bonds:   12.0
TPSA:   108.61
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   4.0 Rings:   2.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.49 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.196 Fsp3:   0.429
MCE-18:   30.0
?
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:   0.149 Fluc inhibitor:   0.012
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.004
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.454
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.365 Promiscuous compounds:   0.384

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.024 MDCK Permeability:   -4.782
Pgp-inhibitor:   0.065 Pgp-substrate:   0.368
PAMPA:   0.011
?
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):   0.011
20% Bioavailability (F20%):   0.046 30% Bioavailability (F30%):   0.028
50% Bioavailability (F50%):   0.8

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.025 MRP1:   0.988
Plasma Protein Binding (PPB):   77.856% Volume Distribution (VD):   -0.28
Fu: 23.347%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.992 BCRP inhibitor:   0.092
BSEP inhibitor:   0.976

ADMET: Metabolism

CYP1A2-inhibitor:   0.019 CYP1A2-substrate:   0.501
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.471
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.868
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.998
CYP3A4-inhibitor:   0.853 CYP3A4-substrate:   0.448
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.944
?
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):  8.337 Half-life (T1/2):  1.688

ADMET: Toxicity

hERG Blockers:  0.126 hERG Blockers (10um):  0.497
Human Hepatotoxicity (H-HT):  0.719 Drug-induced Liver Injury (DILI):  0.042
AMES Toxicity:  0.182 Rat Oral Acute Toxicity:  0.043
Maximum Recommended Daily Dose:  0.159 Skin Sensitization:  0.748
Carcinogencity:  0.245 Eye Corrosion:  0.0
Eye Irritation:  0.295 Respiratory Toxicity:  0.181
Drug-induced Neurotoxicity:  0.17 Ototoxicity:  0.906
Hematotoxicity:  0.204 Drug-induced Nephrotoxicity:  0.25
Genotoxicity:  0.005 RPMI-8226 Immunitoxicity:  0.101
A549 Cytotoxicity:  0.283 Hek293 Cytotoxicity:  0.463
BCF:   1.017
?
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:   3.54
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.931
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.133
?
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
NPO12796 Periploca sepium Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[28294615]
NPO23017 Urtica dioica Species Urticaceae Eukaryota n.a. n.a. n.a. PMID[36447306]
NPO23017 Urtica dioica Species Urticaceae Eukaryota n.a. n.a. n.a. PMID[39696148]
NPO9465 Stelmatocrypton khasianum n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO12796 Periploca sepium Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23017 Urtica dioica Species Urticaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23017 Urtica dioica Species Urticaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO9465 Stelmatocrypton khasianum n.a. n.a. n.a. n.a. n.a. n.a. Database[HerDing]
NPO12796 Periploca sepium Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO9465 Stelmatocrypton khasianum n.a. n.a. n.a. n.a. n.a. n.a. Database[TCMID]
NPO23017 Urtica dioica Species Urticaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12796 Periploca sepium Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23017 Urtica dioica Species Urticaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO12796 Periploca sepium Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO9465 Stelmatocrypton khasianum n.a. n.a. n.a. n.a. n.a. n.a. Database[TCM_Taiwan]
NPO12796 Periploca sepium Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO12796 Periploca sepium Species Apocynaceae 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 NPC105178 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
0.8919 High Similarity NPC85488
0.7619 Intermediate Similarity NPC487676
0.75 Intermediate Similarity NPC607444
0.6585 Remote Similarity NPC165133
0.6585 Remote Similarity NPC242885
0.6585 Remote Similarity NPC95614
0.6585 Remote Similarity NPC193544
0.6585 Remote Similarity NPC232316
0.6383 Remote Similarity NPC5428
0.6341 Remote Similarity NPC221049
0.6136 Remote Similarity NPC17943
0.6111 Remote Similarity NPC486558
0.6087 Remote Similarity NPC476968
0.6047 Remote Similarity NPC255675
0.6 Remote Similarity NPC156840
0.5926 Remote Similarity NPC487677
0.5926 Remote Similarity NPC487675
0.587 Remote Similarity NPC31344
0.587 Remote Similarity NPC317769
0.5849 Remote Similarity NPC273657
0.5818 Remote Similarity NPC282833
0.5814 Remote Similarity NPC471693
0.5745 Remote Similarity NPC56214
0.5714 Remote Similarity NPC98631
0.5714 Remote Similarity NPC206615
0.5714 Remote Similarity NPC257124
0.5714 Remote Similarity NPC610284
0.5625 Remote Similarity NPC227217
0.5625 Remote Similarity NPC117780
0.5581 Remote Similarity NPC8547
0.5581 Remote Similarity NPC140359
0.5556 Remote Similarity NPC184613
0.551 Remote Similarity NPC127587
0.5455 Remote Similarity NPC187998
0.5455 Remote Similarity NPC257582
0.5455 Remote Similarity NPC241522
0.5424 Remote Similarity NPC608199
0.5385 Remote Similarity NPC173308
0.5385 Remote Similarity NPC181079
0.5357 Remote Similarity NPC610652
0.5333 Remote Similarity NPC120852
0.5294 Remote Similarity NPC603109
0.5227 Remote Similarity NPC294327
0.5217 Remote Similarity NPC57490
0.5217 Remote Similarity NPC476343
0.5217 Remote Similarity NPC603326
0.5217 Remote Similarity NPC603989
0.5208 Remote Similarity NPC312675
0.5208 Remote Similarity NPC262156
0.5208 Remote Similarity NPC184651
0.5208 Remote Similarity NPC113865
0.5106 Remote Similarity NPC197757
0.5106 Remote Similarity NPC299406
0.5094 Remote Similarity NPC68779
0.5094 Remote Similarity NPC274356
0.5094 Remote Similarity NPC108598
0.5094 Remote Similarity NPC487680
0.5094 Remote Similarity NPC101748
0.5091 Remote Similarity NPC253481
0.5091 Remote Similarity NPC253722
0.5091 Remote Similarity NPC475875
0.5088 Remote Similarity NPC23646
0.5088 Remote Similarity NPC485397
0.5085 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 NPC105178 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
0.5714 Remote Similarity NPD228 Phase 0

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