Natural Product: NPC139274

Natural Product IDNPC139274
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 MFIHSKBTNZNJIK-WWLNLUSPSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 10454576
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds
      • [CHEMONTID:0003686] Furanoid 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 MFIHSKBTNZNJIK-WWLNLUSPSA-N
Standard InCHI InChI=1S/C23H28O7/c1-24-17-7-6-13(8-18(17)25-2)21-15-11-30-22(16(15)12-29-21)14-9-19(26-3)23(28-5)20(10-14)27-4/h6-10,15-16,21-22H,11-12H2,1-5H3/t15-,16-,21-,22+/m0/s1
SMILES COc1ccc(cc1OC)[C@H]1[C@H]2CO[C@H](c3cc(c(c(c3)OC)OC)OC)[C@H]2CO1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   416.18 Volume:   417.851
?
Van der Waals volume.
Dense:   0.996 LogP:   1.536
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.051
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.863
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   21.0
TPSA:   64.61
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   0.0 Rings:   4.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.68 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.594 Fsp3:   0.478
MCE-18:   77.118
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.347 Fluc inhibitor:   0.509
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.042
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.05
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.289 Promiscuous compounds:   0.291

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.828 MDCK Permeability:   -4.768
Pgp-inhibitor:   0.331 Pgp-substrate:   0.088
PAMPA:   0.001
?
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%):   0.03 30% Bioavailability (F30%):   0.022
50% Bioavailability (F50%):   0.523

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.803 MRP1:   0.998
Plasma Protein Binding (PPB):   80.135% Volume Distribution (VD):   -0.001
Fu: 14.989%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.945
OATP1B3 inhibitor:   0.993 BCRP inhibitor:   0.752
BSEP inhibitor:   0.99

ADMET: Metabolism

CYP1A2-inhibitor:   0.998 CYP1A2-substrate:   0.501
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.166
CYP2C9-inhibitor:   0.132 CYP2C9-substrate:   0.014
CYP2D6-inhibitor:   0.48 CYP2D6-substrate:   0.829
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   0.908
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.862
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):  7.681 Half-life (T1/2):  2.025

ADMET: Toxicity

hERG Blockers:  0.181 hERG Blockers (10um):  0.436
Human Hepatotoxicity (H-HT):  0.799 Drug-induced Liver Injury (DILI):  0.959
AMES Toxicity:  0.715 Rat Oral Acute Toxicity:  0.449
Maximum Recommended Daily Dose:  0.313 Skin Sensitization:  0.871
Carcinogencity:  0.667 Eye Corrosion:  0.04
Eye Irritation:  0.81 Respiratory Toxicity:  0.621
Drug-induced Neurotoxicity:  0.732 Ototoxicity:  0.379
Hematotoxicity:  0.705 Drug-induced Nephrotoxicity:  0.619
Genotoxicity:  0.663 RPMI-8226 Immunitoxicity:  0.23
A549 Cytotoxicity:  0.473 Hek293 Cytotoxicity:  0.355
BCF:   2.28
?
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:   3.811
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.896
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.379
?
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
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. n.a. n.a. PMID[1659613]
NPO18811 Magnolia biondii Species Magnoliaceae Eukaryota n.a. flower bud n.a. PMID[17628872]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota stem bark n.a. n.a. PMID[17918910]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota Stems; Barks n.a. n.a. PMID[19086868]
NPO18811 Magnolia biondii Species Magnoliaceae Eukaryota n.a. n.a. n.a. PMID[19370929]
NPO25197 Magnolia sprengeri Species Magnoliaceae Eukaryota n.a. n.a. n.a. PMID[22080044]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. bark n.a. PMID[23823874]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. n.a. n.a. PMID[28485933]
NPO18811 Magnolia biondii Species Magnoliaceae Eukaryota n.a. flower bud n.a. PMID[7779269]
NPO13730 Magnolia liliiflora Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25197 Magnolia sprengeri Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18811 Magnolia biondii Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15064 Magnolia denudata Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1918 Magnolia kobus Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30851 Magnolia liliflora Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15294 Magnolia salicifolia Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1918 Magnolia kobus Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO25197 Magnolia sprengeri Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO30851 Magnolia liliflora Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18811 Magnolia biondii Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15294 Magnolia salicifolia Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15064 Magnolia denudata Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO1918 Magnolia kobus Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO25197 Magnolia sprengeri Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15294 Magnolia salicifolia Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18811 Magnolia biondii Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15064 Magnolia denudata Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO13730 Magnolia liliiflora Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15294 Magnolia salicifolia Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO15064 Magnolia denudata Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO30851 Magnolia liliflora Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO18811 Magnolia biondii Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO1918 Magnolia kobus Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO25197 Magnolia sprengeri Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO15294 Magnolia salicifolia Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO18811 Magnolia biondii Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO15064 Magnolia denudata Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO25197 Magnolia sprengeri Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15294 Magnolia salicifolia Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18811 Magnolia biondii Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15064 Magnolia denudata Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1918 Magnolia kobus Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13730 Magnolia liliiflora Species Magnoliaceae 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 NPC139274 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 NPC222127
1.0 High Similarity NPC82862
0.8889 High Similarity NPC121783
0.8889 High Similarity NPC34902
0.8889 High Similarity NPC18449
0.8056 Intermediate Similarity NPC281864
0.8056 Intermediate Similarity NPC328682
0.8056 Intermediate Similarity NPC54321
0.7907 Intermediate Similarity NPC189474
0.7442 Intermediate Similarity NPC227160
0.7442 Intermediate Similarity NPC82111
0.7381 Intermediate Similarity NPC606146
0.7073 Intermediate Similarity NPC473092
0.7073 Intermediate Similarity NPC473093
0.7073 Intermediate Similarity NPC8050
0.6809 Remote Similarity NPC27843
0.6809 Remote Similarity NPC7171
0.6744 Remote Similarity NPC148893
0.6744 Remote Similarity NPC25333
0.6744 Remote Similarity NPC49235
0.6667 Remote Similarity NPC50683
0.6667 Remote Similarity NPC112571
0.6667 Remote Similarity NPC285725
0.6591 Remote Similarity NPC165155
0.6591 Remote Similarity NPC24490
0.6522 Remote Similarity NPC488505
0.6512 Remote Similarity NPC171928
0.6512 Remote Similarity NPC158526
0.6512 Remote Similarity NPC129687
0.6512 Remote Similarity NPC33611
0.6512 Remote Similarity NPC16830
0.6512 Remote Similarity NPC100223
0.6275 Remote Similarity NPC474139
0.6087 Remote Similarity NPC209229
0.6078 Remote Similarity NPC298317
0.6078 Remote Similarity NPC255566
0.5714 Remote Similarity NPC216929
0.5714 Remote Similarity NPC312713
0.5714 Remote Similarity NPC126935
0.5714 Remote Similarity NPC65933
0.5714 Remote Similarity NPC57268
0.5714 Remote Similarity NPC172676
0.566 Remote Similarity NPC62354
0.566 Remote Similarity NPC483653
0.5556 Remote Similarity NPC88640
0.5556 Remote Similarity NPC101153
0.5556 Remote Similarity NPC193666
0.5556 Remote Similarity NPC123526
0.5556 Remote Similarity NPC608725
0.5517 Remote Similarity NPC246947
0.551 Remote Similarity NPC136750
0.551 Remote Similarity NPC266848
0.549 Remote Similarity NPC185071
0.5455 Remote Similarity NPC141765
0.5455 Remote Similarity NPC34103
0.5345 Remote Similarity NPC276753
0.5345 Remote Similarity NPC205796
0.5319 Remote Similarity NPC115207
0.5319 Remote Similarity NPC158079
0.5319 Remote Similarity NPC228346
0.5319 Remote Similarity NPC40432
0.5319 Remote Similarity NPC161557
0.5283 Remote Similarity NPC30890
0.5283 Remote Similarity NPC206882
0.52 Remote Similarity NPC126409
0.52 Remote Similarity NPC99572
0.5172 Remote Similarity NPC40094
0.5102 Remote Similarity NPC312199

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC139274 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