Natural Product: NPC59170

Natural Product IDNPC59170
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Phyllostachysin F
IUPAC Name n.a.
Synonyms Phyllostachysin F
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1163642
PubChem CID 16081680
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001551] Diterpenoids
          • [CHEMONTID:0003782] Kaurane diterpenoids

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 JHBXJYSJVIFEFY-FPARTEGVSA-N
Standard InCHI InChI=1S/C20H30O4/c1-10-11-8-12(21)15-19(4)7-5-6-18(2,3)13(19)9-14(22)20(15,16(10)23)17(11)24/h11-15,17,21-22,24H,1,5-9H2,2-4H3/t11-,12-,13+,14+,15-,17+,19+,20+/m0/s1
SMILES C=C1[C@@H]2C[C@@H]([C@H]3[C@]4(C)CCCC(C)(C)[C@H]4C[C@H]([C@@]3(C1=O)[C@@H]2O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   334.21 Volume:   350.138
?
Van der Waals volume.
Dense:   0.955 LogP:   2.432
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.686
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.475
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   21.0
TPSA:   77.76
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   3.0 Rings:   4.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.593 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.954 Fsp3:   0.85
MCE-18:   108.946
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.376 Fluc inhibitor:   0.0
?
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:   0.0
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.307 Promiscuous compounds:   0.051

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.435 MDCK Permeability:   -5.027
Pgp-inhibitor:   0.271 Pgp-substrate:   0.239
PAMPA:   0.953
?
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):   0.268
20% Bioavailability (F20%):   0.679 30% Bioavailability (F30%):   0.749
50% Bioavailability (F50%):   0.956

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.047 MRP1:   0.549
Plasma Protein Binding (PPB):   67.829% Volume Distribution (VD):   -0.114
Fu: 27.327%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.993 BCRP inhibitor:   0.052
BSEP inhibitor:   0.939

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.005
CYP2C19-inhibitor:   0.004 CYP2C19-substrate:   0.051
CYP2C9-inhibitor:   0.007 CYP2C9-substrate:   0.177
CYP2D6-inhibitor:   0.003 CYP2D6-substrate:   0.027
CYP3A4-inhibitor:   0.011 CYP3A4-substrate:   0.756
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.273
HLM stability:   0.623
?
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):  6.667 Half-life (T1/2):  2.406

ADMET: Toxicity

hERG Blockers:  0.02 hERG Blockers (10um):  0.139
Human Hepatotoxicity (H-HT):  0.753 Drug-induced Liver Injury (DILI):  0.835
AMES Toxicity:  0.609 Rat Oral Acute Toxicity:  0.325
Maximum Recommended Daily Dose:  0.81 Skin Sensitization:  0.954
Carcinogencity:  0.829 Eye Corrosion:  0.008
Eye Irritation:  0.574 Respiratory Toxicity:  0.781
Drug-induced Neurotoxicity:  0.161 Ototoxicity:  0.763
Hematotoxicity:  0.794 Drug-induced Nephrotoxicity:  0.955
Genotoxicity:  0.826 RPMI-8226 Immunitoxicity:  0.195
A549 Cytotoxicity:  0.217 Hek293 Cytotoxicity:  0.415
BCF:   0.71
?
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:   3.347
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.966
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.059
?
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
NPO28626.2 Isodon rubescens var. lushiensis Varieties Lamiaceae Eukaryota n.a. n.a. n.a. PMID[14575445]
NPO28626.2 Isodon rubescens var. lushiensis Varieties Lamiaceae Eukaryota n.a. n.a. n.a. PMID[20521771]
NPO15942 Isodon wikstroemioides Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[24697496]
NPO28626.2 Isodon rubescens var. lushiensis Varieties Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15942 Isodon wikstroemioides Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28626.2 Isodon rubescens var. lushiensis Varieties Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28626.2 Isodon rubescens var. lushiensis Varieties Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15942 Isodon wikstroemioides Species Lamiaceae 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
NPT116 Cell line HL-60 Homo sapiens IC50 = 850.0 nM PMID[16724846]
NPT81 Cell line A549 Homo sapiens IC50 = 3300.0 nM PubChem BioAssay data set
NPT134 Cell line SK-BR-3 Homo sapiens IC50 = 3300.0 nM PubChem BioAssay data set
NPT461 Cell line PANC-1 Homo sapiens IC50 = 4500.0 nM PMID[8786361]
NPT659 Cell line SMMC-7721 Homo sapiens IC50 = 5500.0 nM PMID[8786361]
NPT113 Cell line RAW264.7 Mus musculus IC50 = 1000.0 nM PMID[22738356]
NPT660 Cell line SW480 Homo sapiens IC50 = 1100.0 nM PMID[22738356]
NPT83 Cell line MCF7 Homo sapiens IC50 = 1500.0 nM PMID[22746380]
NPT659 Cell line SMMC-7721 Homo sapiens IC50 = 2100.0 nM PMID[19654408]
NPT81 Cell line A549 Homo sapiens IC50 = 2300.0 nM PMID[20421398]
NPT116 Cell line HL-60 Homo sapiens IC50 = 3300.0 nM PMID[24864039]

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 NPC59170 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
0.8043 Intermediate Similarity NPC231060
0.7872 Intermediate Similarity NPC29112
0.75 Intermediate Similarity NPC84018
0.7083 Intermediate Similarity NPC165895
0.7083 Intermediate Similarity NPC127408
0.6939 Remote Similarity NPC16164
0.6875 Remote Similarity NPC138245
0.6792 Remote Similarity NPC87927
0.6415 Remote Similarity NPC132813
0.6415 Remote Similarity NPC147965
0.62 Remote Similarity NPC129004
0.5849 Remote Similarity NPC55503
0.566 Remote Similarity NPC291785
0.566 Remote Similarity NPC149761
0.5577 Remote Similarity NPC302008
0.5556 Remote Similarity NPC59350
0.5472 Remote Similarity NPC278106
0.5455 Remote Similarity NPC60947
0.5455 Remote Similarity NPC64006
0.5345 Remote Similarity NPC231278
0.5345 Remote Similarity NPC469746
0.5283 Remote Similarity NPC261994
0.5283 Remote Similarity NPC470378
0.5254 Remote Similarity NPC13149
0.5185 Remote Similarity NPC181594
0.5185 Remote Similarity NPC299185
0.5179 Remote Similarity NPC41070
0.5167 Remote Similarity NPC112895
0.5091 Remote Similarity NPC179399
0.5091 Remote Similarity NPC118800
0.5091 Remote Similarity NPC104371
0.5091 Remote Similarity NPC291320
0.5091 Remote Similarity NPC471036
0.5088 Remote Similarity NPC142352
0.5085 Remote Similarity NPC16911
0.5082 Remote Similarity NPC469729

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC59170 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