Natural Product: NPC191012

Natural Product IDNPC191012
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 13-Hydroxy-14-Oxocacalohastin
IUPAC Name (5S)-3-(hydroxymethyl)-9-methoxy-5-methyl-5,6-dihydrobenzo[f][1]benzofuran-4-carbaldehyde
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL463711
PubChem CID 637824
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001550] Sesquiterpenoids
          • [CHEMONTID:0003655] Eremophilane, 8,9-secoeremophilane and furoeremophilane sesquiterpenoids

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 OGSLGCUQMDVTNB-VIFPVBQESA-N
Standard InCHI InChI=1S/C16H16O4/c1-9-4-3-5-11-13(9)12(7-18)14-10(6-17)8-20-16(14)15(11)19-2/h3,5,7-9,17H,4,6H2,1-2H3/t9-/m0/s1
SMILES C[C@H]1CC=Cc2c1c(C=O)c1c(CO)coc1c2OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   272.1 Volume:   278.965
?
Van der Waals volume.
Dense:   0.975 LogP:   2.275
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.53
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.612
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   16.0
TPSA:   59.67
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.871 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.95 Fsp3:   0.312
MCE-18:   54.238
?
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:   0.535 Fluc inhibitor:   0.285
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.594
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.69
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.156 Promiscuous compounds:   0.407

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.985 MDCK Permeability:   -4.742
Pgp-inhibitor:   0.638 Pgp-substrate:   0.651
PAMPA:   0.164
?
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):   0.077
20% Bioavailability (F20%):   0.329 30% Bioavailability (F30%):   0.905
50% Bioavailability (F50%):   0.887

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.724 MRP1:   0.896
Plasma Protein Binding (PPB):   77.871% Volume Distribution (VD):   0.356
Fu: 23.614%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.877
OATP1B3 inhibitor:   0.798 BCRP inhibitor:   0.587
BSEP inhibitor:   0.975

ADMET: Metabolism

CYP1A2-inhibitor:   0.018 CYP1A2-substrate:   0.244
CYP2C19-inhibitor:   0.277 CYP2C19-substrate:   0.156
CYP2C9-inhibitor:   0.581 CYP2C9-substrate:   0.345
CYP2D6-inhibitor:   0.125 CYP2D6-substrate:   0.585
CYP3A4-inhibitor:   0.215 CYP3A4-substrate:   0.932
CYP2B6-substrate:   0.002 CYP2C8-inhibitor:   0.987
HLM stability:   0.738
?
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):  8.812 Half-life (T1/2):  1.02

ADMET: Toxicity

hERG Blockers:  0.059 hERG Blockers (10um):  0.291
Human Hepatotoxicity (H-HT):  0.655 Drug-induced Liver Injury (DILI):  0.744
AMES Toxicity:  0.766 Rat Oral Acute Toxicity:  0.407
Maximum Recommended Daily Dose:  0.75 Skin Sensitization:  0.731
Carcinogencity:  0.918 Eye Corrosion:  0.033
Eye Irritation:  0.887 Respiratory Toxicity:  0.71
Drug-induced Neurotoxicity:  0.315 Ototoxicity:  0.402
Hematotoxicity:  0.466 Drug-induced Nephrotoxicity:  0.365
Genotoxicity:  0.623 RPMI-8226 Immunitoxicity:  0.136
A549 Cytotoxicity:  0.133 Hek293 Cytotoxicity:  0.281
BCF:   1.111
?
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:   3.704
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.634
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.759
?
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
NPO19205 Buxus sempervirens Species Buxaceae Eukaryota roots n.a. n.a. PMID[10346940]
NPO12724 Roldana angulifolia Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[17190472]
NPO16980 Callistemon lanceolatus Species Myrtaceae Eukaryota n.a. leaf n.a. PMID[18618463]
NPO16980 Callistemon lanceolatus Species Myrtaceae Eukaryota n.a. flower n.a. PMID[18618463]
NPO19205 Buxus sempervirens Species Buxaceae Eukaryota n.a. n.a. n.a. PMID[26722868]
NPO17352 Streptomyces mutabilis Species Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[27107984]
NPO17626 Gentiana algida Species Gentianaceae Eukaryota n.a. whole plant n.a. PMID[8588862]
NPO12724 Roldana angulifolia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17352 Streptomyces mutabilis Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO17896 Perymenium discolor Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16980 Callistemon lanceolatus Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19205 Buxus sempervirens Species Buxaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17626 Gentiana algida Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19205 Buxus sempervirens Species Buxaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11820 Amomum villosum Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO17626 Gentiana algida Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11820 Amomum villosum Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29168 Jacobaea abrotanifolia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO19205 Buxus sempervirens Species Buxaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17626 Gentiana algida Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO19205 Buxus sempervirens Species Buxaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO11820 Amomum villosum Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO12724 Roldana angulifolia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19205 Buxus sempervirens Species Buxaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12869 Quercus gambelii Species Fagaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17113 Pertusaria sulphurata Species Pertusariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18531 Streptomyces propurpuratus Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO17896 Perymenium discolor Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16980 Callistemon lanceolatus Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29168 Jacobaea abrotanifolia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17626 Gentiana algida Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15290.1 Petasites frigidus var. palmatus Varieties Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17352 Streptomyces mutabilis Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO11820 Amomum villosum 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

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT380 Cell line U-251 Homo sapiens IC50 > 10000.0 nM PMID[17190472]
NPT306 Cell line PC-3 Homo sapiens IC50 > 10000.0 nM PMID[17190472]
NPT111 Cell line K562 Homo sapiens IC50 > 10000.0 nM PMID[17190472]
NPT148 Cell line HCT-15 Homo sapiens IC50 > 10000.0 nM PMID[17190472]
NPT83 Cell line MCF7 Homo sapiens IC50 > 10000.0 nM PMID[17190472]
NPT311 Cell line SK-LU-1 Homo sapiens IC50 > 10000.0 nM PMID[17190472]

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 NPC191012 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
0.6825 Remote Similarity NPC132054
0.6379 Remote Similarity NPC603823

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC191012 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