Natural Product: NPC31751

Natural Product IDNPC31751
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (-)-Trachelogenin
IUPAC Name (3S,4S)-4-[(3,4-dimethoxyphenyl)methyl]-3-hydroxy-3-[(4-hydroxy-3-methoxyphenyl)methyl]oxolan-2-one
Synonyms (-)-Trachelogenin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL491178
PubChem CID 452855
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
            • [CHEMONTID:0001613] Dibenzylbutyrolactone 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 YFVZKLQNMNKWSB-BTYIYWSLSA-N
Standard InCHI InChI=1S/C21H24O7/c1-25-17-7-5-13(9-19(17)27-3)8-15-12-28-20(23)21(15,24)11-14-4-6-16(22)18(10-14)26-2/h4-7,9-10,15,22,24H,8,11-12H2,1-3H3/t15-,21-/m0/s1
SMILES COc1ccc(C[C@H]2COC(=O)[C@@]2(Cc2ccc(c(c2)OC)O)O)cc1OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   388.15 Volume:   389.179
?
Van der Waals volume.
Dense:   0.997 LogP:   1.274
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.579
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.731
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   18.0
TPSA:   94.45
?
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:   0.702 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.266 Fsp3:   0.381
MCE-18:   64.138
?
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:   0.091 Fluc inhibitor:   0.056
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.014
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.424
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.227 Promiscuous compounds:   0.141

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.075 MDCK Permeability:   -4.723
Pgp-inhibitor:   0.199 Pgp-substrate:   0.531
PAMPA:   0.062
?
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):   0.005
20% Bioavailability (F20%):   0.636 30% Bioavailability (F30%):   0.405
50% Bioavailability (F50%):   0.772

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.944
Plasma Protein Binding (PPB):   87.782% Volume Distribution (VD):   -0.046
Fu: 12.266%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.995
OATP1B3 inhibitor:   0.965 BCRP inhibitor:   0.02
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.981 CYP1A2-substrate:   0.802
CYP2C19-inhibitor:   0.984 CYP2C19-substrate:   0.996
CYP2C9-inhibitor:   0.332 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.022 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   0.999
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.986
?
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):  4.802 Half-life (T1/2):  2.789

ADMET: Toxicity

hERG Blockers:  0.075 hERG Blockers (10um):  0.446
Human Hepatotoxicity (H-HT):  0.803 Drug-induced Liver Injury (DILI):  0.908
AMES Toxicity:  0.866 Rat Oral Acute Toxicity:  0.152
Maximum Recommended Daily Dose:  0.561 Skin Sensitization:  0.878
Carcinogencity:  0.803 Eye Corrosion:  0.005
Eye Irritation:  0.844 Respiratory Toxicity:  0.204
Drug-induced Neurotoxicity:  0.663 Ototoxicity:  0.539
Hematotoxicity:  0.477 Drug-induced Nephrotoxicity:  0.825
Genotoxicity:  0.988 RPMI-8226 Immunitoxicity:  0.16
A549 Cytotoxicity:  0.125 Hek293 Cytotoxicity:  0.373
BCF:   0.878
?
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:   3.641
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.751
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.256
?
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
NPO13014 Ipomoea cairica Species Convolvulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12235 Trachelospermum jasminoides Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13014 Ipomoea cairica Species Convolvulaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12235 Trachelospermum jasminoides Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14834 Trachelospermum asiaticum Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO13014 Ipomoea cairica Species Convolvulaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12235 Trachelospermum jasminoides Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14834 Trachelospermum asiaticum Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12235 Trachelospermum jasminoides Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO13014 Ipomoea cairica Species Convolvulaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO12235 Trachelospermum jasminoides Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO14834 Trachelospermum asiaticum Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO12235 Trachelospermum jasminoides Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13014 Ipomoea cairica Species Convolvulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14834 Trachelospermum asiaticum 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
NPT1114 Organism Human immunodeficiency virus Human immunodeficiency virus Activity = 60.0 % PMID[9834179]
NPT28438 Unchecked Unchecked n.a. IC50 = 670.0 nM PMID[38394369]
NPT2 Others Unspecified n.a. MIC = 57000.0 nM PMID[9834179]
NPT2 Others Unspecified n.a. MIC = 69000.0 nM PMID[9834179]

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 NPC31751 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
0.8846 High Similarity NPC253481
0.8846 High Similarity NPC253722
0.7183 Intermediate Similarity NPC163635
0.629 Remote Similarity NPC300776
0.629 Remote Similarity NPC176814
0.629 Remote Similarity NPC4982
0.629 Remote Similarity NPC606629
0.614 Remote Similarity NPC607444
0.6071 Remote Similarity NPC227217
0.6071 Remote Similarity NPC117780
0.5588 Remote Similarity NPC169973
0.5493 Remote Similarity NPC478703
0.5493 Remote Similarity NPC478704
0.5441 Remote Similarity NPC487679
0.5441 Remote Similarity NPC64201
0.5441 Remote Similarity NPC487678
0.5439 Remote Similarity NPC31344
0.5439 Remote Similarity NPC317769
0.5362 Remote Similarity NPC282291
0.5362 Remote Similarity NPC166137
0.5323 Remote Similarity NPC68779
0.5323 Remote Similarity NPC108598
0.5323 Remote Similarity NPC173308
0.5323 Remote Similarity NPC181079
0.5323 Remote Similarity NPC487680
0.5303 Remote Similarity NPC110699
0.5303 Remote Similarity NPC481088
0.5303 Remote Similarity NPC106920
0.5303 Remote Similarity NPC15811
0.5303 Remote Similarity NPC23646
0.5303 Remote Similarity NPC106055
0.5303 Remote Similarity NPC485397
0.5224 Remote Similarity NPC90431
0.5147 Remote Similarity NPC485282
0.5147 Remote Similarity NPC485283
0.5147 Remote Similarity NPC485281
0.5143 Remote Similarity NPC471988
0.5082 Remote Similarity NPC5428
0.5079 Remote Similarity NPC274356
0.5079 Remote Similarity NPC101748

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC31751 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