Natural Product: NPC132078

Natural Product IDNPC132078
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (-)-Centrolobol
IUPAC Name 4-[(5R)-5-hydroxy-7-(4-hydroxyphenyl)heptyl]phenol
Synonyms (-)-Centrolobol
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL462922
PubChem CID 11771038
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002650] Diarylheptanoids
        • [CHEMONTID:0002651] Linear diarylheptanoids

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 UYJAYWZGEZOHRU-QGZVFWFLSA-N
Standard InCHI InChI=1S/C19H24O3/c20-17(10-7-16-8-13-19(22)14-9-16)4-2-1-3-15-5-11-18(21)12-6-15/h5-6,8-9,11-14,17,20-22H,1-4,7,10H2/t17-/m1/s1
SMILES C(CC[C@H](CCc1ccc(cc1)O)O)Cc1ccc(cc1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   300.17 Volume:   330.619
?
Van der Waals volume.
Dense:   0.908 LogP:   2.94
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.366
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.896
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   8.0 Rigid Bonds:   12.0
TPSA:   60.69
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   3.0 Rings:   2.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.65 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.373 Fsp3:   0.368
MCE-18:   22.0
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.523 Fluc inhibitor:   0.316
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.006
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.032
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.673 Promiscuous compounds:   0.232

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.022 MDCK Permeability:   -4.796
Pgp-inhibitor:   0.307 Pgp-substrate:   0.744
PAMPA:   0.036
?
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%):   0.278 30% Bioavailability (F30%):   0.998
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.073
Plasma Protein Binding (PPB):   89.215% Volume Distribution (VD):   -0.372
Fu: 9.498%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.997
OATP1B3 inhibitor:   0.943 BCRP inhibitor:   0.859
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.062 CYP1A2-substrate:   0.01
CYP2C19-inhibitor:   0.777 CYP2C19-substrate:   0.022
CYP2C9-inhibitor:   0.037 CYP2C9-substrate:   0.31
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.964
CYP3A4-inhibitor:   0.122 CYP3A4-substrate:   0.007
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.984
HLM stability:   0.921
?
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):  10.693 Half-life (T1/2):  1.027

ADMET: Toxicity

hERG Blockers:  0.65 hERG Blockers (10um):  0.889
Human Hepatotoxicity (H-HT):  0.743 Drug-induced Liver Injury (DILI):  0.026
AMES Toxicity:  0.146 Rat Oral Acute Toxicity:  0.038
Maximum Recommended Daily Dose:  0.777 Skin Sensitization:  0.94
Carcinogencity:  0.167 Eye Corrosion:  0.297
Eye Irritation:  0.989 Respiratory Toxicity:  0.502
Drug-induced Neurotoxicity:  0.364 Ototoxicity:  0.618
Hematotoxicity:  0.07 Drug-induced Nephrotoxicity:  0.839
Genotoxicity:  0.006 RPMI-8226 Immunitoxicity:  0.037
A549 Cytotoxicity:  0.56 Hek293 Cytotoxicity:  0.793
BCF:   1.554
?
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:   4.268
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.989
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.712
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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
NPO30634 Acer nikoense Species Sapindaceae Eukaryota n.a. Japan n.a. PMID[12542351]
NPO4138 Betula platyphylla Species Betulaceae Eukaryota bark n.a. n.a. PMID[20363129]
NPO30634 Acer nikoense Species Sapindaceae Eukaryota n.a. n.a. n.a. PMID[21550801]
NPO4138 Betula platyphylla Species Betulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30634 Acer nikoense Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30634 Acer nikoense Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO4138 Betula platyphylla Species Betulaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO4138 Betula platyphylla Species Betulaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO4138 Betula platyphylla Species Betulaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO4138 Betula platyphylla Species Betulaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO4138 Betula platyphylla Species Betulaceae 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
NPT521 Cell line RBL-2H3 Rattus norvegicus Inhibition = 19.22 % DrugMatrix in vitro pharmacology data
NPT521 Cell line RBL-2H3 Rattus norvegicus Inhibition = 31.5 % PMID[19191549]
NPT113 Cell line RAW264.7 Mus musculus Inhibition = 29.0 % PMID[33422907]
NPT113 Cell line RAW264.7 Mus musculus Activity = 52.0 % PMID[33422907]
NPT113 Cell line RAW264.7 Mus musculus IC50 = 27800.0 nM PMID[33422907]
NPT28833 No target No relevant target n.a. IC50 = 44400.0 nM PMID[33422907]
NPT2 Others Unspecified n.a. Inhibition = -1.3 % PMID[26222905]
NPT2 Others Unspecified n.a. Inhibition = 1.3 % PMID[26222905]
NPT2 Others Unspecified n.a. Inhibition = -1.1 % PMID[25497963]
NPT2 Others Unspecified n.a. Inhibition = 10.7 % Open TG-GATES in vivo data: Biochemistry
NPT2 Others Unspecified n.a. Inhibition = 67.2 % PMID[22280816]
NPT2 Others Unspecified n.a. IC50 = 73000.0 nM Open TG-GATES in vivo data: Biochemistry

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT32 Organism Mus musculus Mus musculus ID50 = 0.66 mg PMID[33422907]





 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 NPC132078 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 NPC600556
0.8421 Intermediate Similarity NPC226401
0.8421 Intermediate Similarity NPC174096
0.7368 Intermediate Similarity NPC120982
0.6857 Remote Similarity NPC91461
0.6857 Remote Similarity NPC7686
0.6857 Remote Similarity NPC40258
0.6829 Remote Similarity NPC262365
0.6579 Remote Similarity NPC213730
0.6286 Remote Similarity NPC138117
0.6286 Remote Similarity NPC325292
0.6286 Remote Similarity NPC242240
0.6 Remote Similarity NPC474839
0.5946 Remote Similarity NPC123273
0.5946 Remote Similarity NPC318325
0.5909 Remote Similarity NPC216468
0.5909 Remote Similarity NPC78119
0.587 Remote Similarity NPC51333
0.5854 Remote Similarity NPC179002
0.5854 Remote Similarity NPC257430
0.58 Remote Similarity NPC127389
0.58 Remote Similarity NPC290451
0.58 Remote Similarity NPC17109
0.5714 Remote Similarity NPC23167
0.5581 Remote Similarity NPC177576
0.5435 Remote Similarity NPC321252
0.5435 Remote Similarity NPC252544
0.5333 Remote Similarity NPC475018
0.5217 Remote Similarity NPC249435
0.5185 Remote Similarity NPC241964
0.5143 Remote Similarity NPC608485
0.5116 Remote Similarity NPC261573
0.5106 Remote Similarity NPC317305
0.5106 Remote Similarity NPC186843
0.5102 Remote Similarity NPC147634
0.5102 Remote Similarity NPC79793

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC132078 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