Natural Product: NPC177576

Natural Product IDNPC177576
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Platyphyllone
IUPAC Name (5S)-5-hydroxy-1,7-bis(4-hydroxyphenyl)heptan-3-one
Synonyms Platyphyllone
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1087992
PubChem CID 13347313
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002650] Diarylheptanoids
        • [CHEMONTID:0002651] Linear diarylheptanoids
          • [CHEMONTID:0000356] Curcuminoids

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 ZBFSUZGUYFFWGY-SFHVURJKSA-N
Standard InCHI InChI=1S/C19H22O4/c20-16-7-1-14(2-8-16)5-11-18(22)13-19(23)12-6-15-3-9-17(21)10-4-15/h1-4,7-10,18,20-22H,5-6,11-13H2/t18-/m0/s1
SMILES O[C@H](CC(=O)CCc1ccc(cc1)O)CCc1ccc(cc1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   314.15 Volume:   336.773
?
Van der Waals volume.
Dense:   0.933 LogP:   2.123
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.111
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.643
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   8.0 Rigid Bonds:   13.0
TPSA:   77.76
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   3.0 Rings:   2.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.7 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.536 Fsp3:   0.316
MCE-18:   24.0
?
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:   0.507 Fluc inhibitor:   0.27
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.011
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.117
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.67 Promiscuous compounds:   0.219

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.006 MDCK Permeability:   -4.798
Pgp-inhibitor:   0.991 Pgp-substrate:   0.474
PAMPA:   0.228
?
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%):   0.142 30% Bioavailability (F30%):   0.996
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.006
Plasma Protein Binding (PPB):   85.521% Volume Distribution (VD):   -0.102
Fu: 16.602%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.987 BCRP inhibitor:   0.676
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.002 CYP1A2-substrate:   0.003
CYP2C19-inhibitor:   0.604 CYP2C19-substrate:   0.016
CYP2C9-inhibitor:   0.096 CYP2C9-substrate:   0.108
CYP2D6-inhibitor:   0.998 CYP2D6-substrate:   0.933
CYP3A4-inhibitor:   0.271 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.908
HLM stability:   0.825
?
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):  11.695 Half-life (T1/2):  1.2

ADMET: Toxicity

hERG Blockers:  0.464 hERG Blockers (10um):  0.779
Human Hepatotoxicity (H-HT):  0.814 Drug-induced Liver Injury (DILI):  0.015
AMES Toxicity:  0.127 Rat Oral Acute Toxicity:  0.076
Maximum Recommended Daily Dose:  0.876 Skin Sensitization:  0.871
Carcinogencity:  0.229 Eye Corrosion:  0.049
Eye Irritation:  0.969 Respiratory Toxicity:  0.199
Drug-induced Neurotoxicity:  0.751 Ototoxicity:  0.675
Hematotoxicity:  0.107 Drug-induced Nephrotoxicity:  0.889
Genotoxicity:  0.126 RPMI-8226 Immunitoxicity:  0.031
A549 Cytotoxicity:  0.267 Hek293 Cytotoxicity:  0.661
BCF:   0.872
?
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:   3.13
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.077
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.859
?
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
NPO22901 Curcuma comosa Species Zingiberaceae Eukaryota n.a. n.a. n.a. DOI[10.1021/np100392m]
NPO22741 Curcuma kwangsiensis Species Zingiberaceae Eukaryota n.a. rhizome n.a. DOI[10.1021/np100392m]
NPO4138.1 Betula platyphylla var. japonica Varieties Betulaceae Eukaryota floral spikes n.a. n.a. PMID[17346076]
NPO22901 Curcuma comosa Species Zingiberaceae Eukaryota rhizomes Kampaengsaen district, Nakhon Pathom province, Thailand n.a. PMID[18554915]
NPO15361 Alnus japonica Species Betulaceae Eukaryota bark n.a. n.a. PMID[20045319]
NPO22901 Curcuma comosa Species Zingiberaceae Eukaryota aerial parts n.a. n.a. PMID[20196571]
NPO4138 Betula platyphylla Species Betulaceae Eukaryota bark n.a. n.a. PMID[20363129]
NPO22741 Curcuma kwangsiensis Species Zingiberaceae Eukaryota Rhizomes n.a. n.a. PMID[20879743]
NPO4971 Alnus firma Species Betulaceae Eukaryota n.a. n.a. n.a. PMID[21504848]
NPO22741 Curcuma kwangsiensis Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[21807513]
NPO32876 alnus hirsuta f. sibirica Species Betulaceae Eukaryota n.a. n.a. n.a. PMID[23465614]
NPO22901 Curcuma comosa Species Zingiberaceae Eukaryota rhizomes n.a. n.a. PMID[23910596]
NPO15361 Alnus japonica Species Betulaceae Eukaryota n.a. n.a. n.a. PMID[26341132]
NPO22901 Curcuma comosa Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[8176399]
NPO4138.1 Betula platyphylla var. japonica Varieties Betulaceae Eukaryota bark n.a. n.a. PMID[9873651]
NPO4138.1 Betula platyphylla var. japonica Varieties Betulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO32876 alnus hirsuta f. sibirica Species Betulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4138 Betula platyphylla Species Betulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15361 Alnus japonica Species Betulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4971 Alnus firma Species Betulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22741 Curcuma kwangsiensis Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22901 Curcuma comosa Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4138 Betula platyphylla Species Betulaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO4138.1 Betula platyphylla var. japonica Varieties Betulaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO22741 Curcuma kwangsiensis Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15361 Alnus japonica Species Betulaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO4138.1 Betula platyphylla var. japonica Varieties Betulaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15361 Alnus japonica Species Betulaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO4138 Betula platyphylla Species Betulaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO22741 Curcuma kwangsiensis Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO13049 Alnus spp. Species Betulaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO4138.2 Betula platyphylla suk. var. japonica (sieb.) hara Varieties Betulaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO22741 Curcuma kwangsiensis Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO4138 Betula platyphylla Species Betulaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO15361 Alnus japonica Species Betulaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO22741 Curcuma kwangsiensis Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO4138 Betula platyphylla Species Betulaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO22901 Curcuma comosa Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4971 Alnus firma Species Betulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15361 Alnus japonica Species Betulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4138 Betula platyphylla Species Betulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22741 Curcuma kwangsiensis Species Zingiberaceae 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
NPT43 Individual protein Tyrosinase Agaricus bisporus Inhibition < 17.0 % PMID[23910596]

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 = 23.7 % PMID[20363129]
NPT521 Cell line RBL-2H3 Rattus norvegicus Inhibition = 24.9 % PMID[20363129]
NPT113 Cell line RAW264.7 Mus musculus IC50 = 46370.0 nM PMID[21807513]
NPT520 Cell line 3T3-L1 Mus musculus Activity = 27.5 % PMID[23465614]
NPT520 Cell line 3T3-L1 Mus musculus Activity = 50.7 % PMID[23465614]
NPT520 Cell line 3T3-L1 Mus musculus Activity = 85.2 % PMID[23465614]
NPT113 Cell line RAW264.7 Mus musculus IC50 = 30000.0 nM PMID[33422907]
NPT34 Cell line BV-2 Mus musculus Inhibition = 66.3 % PMID[33422907]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 54900.0 nM PMID[21504848]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 10000.0 nM PMID[23910596]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 31.5 % PMID[23910596]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 19.9 % PMID[23910596]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 12.5 % PMID[23910596]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 16.8 % PMID[23910596]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 13.1 % PMID[23910596]
NPT742 Organism Influenza A virus Influenza A virus EC50 = 29900.0 nM PMID[20045319]
NPT2 Others Unspecified n.a. Ratio > 26.6 n.a. PMID[20045319]

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 NPC177576 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
0.8974 High Similarity NPC321252
0.8974 High Similarity NPC252544
0.8537 High Similarity NPC265454
0.7561 Intermediate Similarity NPC34634
0.7447 Intermediate Similarity NPC215941
0.7447 Intermediate Similarity NPC123196
0.7447 Intermediate Similarity NPC311419
0.7209 Intermediate Similarity NPC317305
0.7179 Intermediate Similarity NPC187725
0.7179 Intermediate Similarity NPC141607
0.7179 Intermediate Similarity NPC310194
0.7045 Intermediate Similarity NPC182240
0.6596 Remote Similarity NPC137427
0.6579 Remote Similarity NPC188677
0.6458 Remote Similarity NPC481913
0.6316 Remote Similarity NPC91461
0.6316 Remote Similarity NPC7686
0.6316 Remote Similarity NPC40258
0.6275 Remote Similarity NPC275724
0.6275 Remote Similarity NPC244246
0.6275 Remote Similarity NPC611247
0.617 Remote Similarity NPC285350
0.6053 Remote Similarity NPC260000
0.5849 Remote Similarity NPC65935
0.5849 Remote Similarity NPC319282
0.5833 Remote Similarity NPC63345
0.5814 Remote Similarity NPC261573
0.5789 Remote Similarity NPC138117
0.5789 Remote Similarity NPC325292
0.5714 Remote Similarity NPC213730
0.5686 Remote Similarity NPC86900
0.5625 Remote Similarity NPC481914
0.5581 Remote Similarity NPC132078
0.5581 Remote Similarity NPC600556
0.5455 Remote Similarity NPC179002
0.5455 Remote Similarity NPC257430
0.5208 Remote Similarity NPC249435
0.5208 Remote Similarity NPC216468
0.5208 Remote Similarity NPC78119
0.5185 Remote Similarity NPC470215
0.5185 Remote Similarity NPC470214
0.5111 Remote Similarity NPC29989
0.5102 Remote Similarity NPC186843
0.5102 Remote Similarity NPC120693
0.5102 Remote Similarity NPC88141

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC177576 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