Natural Product: NPC59350

Natural Product IDNPC59350
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Albopilosin H
IUPAC Name n.a.
Synonyms albopilosin H
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL458481
PubChem CID 11566162
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 ZXYPBEZVRIDTAX-YNDYFHGHSA-N
Standard InCHI InChI=1S/C20H28O4/c1-11-12-5-6-13-19(3)8-4-7-18(2,10-21)14(19)9-15(22)20(13,16(11)23)17(12)24/h10,12-15,17,22,24H,1,4-9H2,2-3H3/t12-,13-,14+,15+,17+,18+,19-,20-/m0/s1
SMILES O=C[C@@]1(C)CCC[C@@]2([C@@H]1C[C@@H](O)[C@@]13[C@H]2CC[C@H]([C@H]3O)C(=C)C1=O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   332.2 Volume:   347.502
?
Van der Waals volume.
Dense:   0.956 LogP:   2.507
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.833
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.378
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   22.0
TPSA:   74.6
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.571 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   6.064 Fsp3:   0.8
MCE-18:   105.778
?
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:   0.426 Fluc inhibitor:   0.001
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.026
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.002
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.337 Promiscuous compounds:   0.142

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.14 MDCK Permeability:   -4.818
Pgp-inhibitor:   0.769 Pgp-substrate:   0.153
PAMPA:   0.699
?
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):   0.193
20% Bioavailability (F20%):   0.424 30% Bioavailability (F30%):   0.667
50% Bioavailability (F50%):   0.946

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.061 MRP1:   0.538
Plasma Protein Binding (PPB):   72.205% Volume Distribution (VD):   0.18
Fu: 30.95%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.434
BSEP inhibitor:   0.988

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.022
CYP2C19-inhibitor:   0.004 CYP2C19-substrate:   0.912
CYP2C9-inhibitor:   0.103 CYP2C9-substrate:   0.202
CYP2D6-inhibitor:   0.005 CYP2D6-substrate:   0.012
CYP3A4-inhibitor:   0.152 CYP3A4-substrate:   0.598
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.974
HLM stability:   0.093
?
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):  9.288 Half-life (T1/2):  1.988

ADMET: Toxicity

hERG Blockers:  0.024 hERG Blockers (10um):  0.188
Human Hepatotoxicity (H-HT):  0.829 Drug-induced Liver Injury (DILI):  0.798
AMES Toxicity:  0.66 Rat Oral Acute Toxicity:  0.654
Maximum Recommended Daily Dose:  0.915 Skin Sensitization:  0.961
Carcinogencity:  0.932 Eye Corrosion:  0.002
Eye Irritation:  0.375 Respiratory Toxicity:  0.88
Drug-induced Neurotoxicity:  0.268 Ototoxicity:  0.632
Hematotoxicity:  0.682 Drug-induced Nephrotoxicity:  0.87
Genotoxicity:  0.98 RPMI-8226 Immunitoxicity:  0.204
A549 Cytotoxicity:  0.313 Hek293 Cytotoxicity:  0.503
BCF:   0.614
?
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:   3.463
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.025
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.182
?
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
NPO23065 Isodon albopilosus Species Lamiaceae Eukaryota aerial parts Maoxian, Sichuan Province, China 2004-JUL PMID[16378369]
NPO23065 Isodon albopilosus Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[17497809]
NPO23065 Isodon albopilosus Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23065 Isodon albopilosus Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO23065 Isodon albopilosus Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23065 Isodon albopilosus 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
NPT65 Cell line HepG2 Homo sapiens IC50 = 13310.0 nM PMID[16378369]

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 NPC59350 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
0.7872 Intermediate Similarity NPC165895
0.7708 Intermediate Similarity NPC149761
0.72 Intermediate Similarity NPC29112
0.7 Intermediate Similarity NPC135548
0.6939 Remote Similarity NPC261994
0.6939 Remote Similarity NPC470378
0.6923 Remote Similarity NPC142352
0.6852 Remote Similarity NPC16911
0.6667 Remote Similarity NPC180849
0.6471 Remote Similarity NPC299185
0.6182 Remote Similarity NPC78427
0.6154 Remote Similarity NPC181594
0.6078 Remote Similarity NPC111524
0.5636 Remote Similarity NPC144739
0.5593 Remote Similarity NPC287676
0.5556 Remote Similarity NPC59170
0.5455 Remote Similarity NPC231060
0.5424 Remote Similarity NPC163963
0.537 Remote Similarity NPC129004
0.5345 Remote Similarity NPC289148
0.5345 Remote Similarity NPC214946
0.5273 Remote Similarity NPC91772
0.5263 Remote Similarity NPC41070
0.5263 Remote Similarity NPC64006
0.5254 Remote Similarity NPC52899
0.5254 Remote Similarity NPC327247
0.5185 Remote Similarity NPC102292
0.5179 Remote Similarity NPC264979
0.5088 Remote Similarity NPC483200

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC59350 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