Natural Product: NPC13149

Natural Product IDNPC13149
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Pseudoirroratin A
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL517614
PubChem CID 637422
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 NDYPVJHBSKUXPP-VWIBHASISA-N
Standard InCHI InChI=1S/C20H28O5/c1-10-11-8-19(24)16-18(9-25-19)6-4-5-17(2,3)12(18)7-13(21)20(16,14(10)22)15(11)23/h11-13,15-16,21,23-24H,1,4-9H2,2-3H3/t11-,12+,13+,15+,16+,18-,19+,20+/m0/s1
SMILES C=C1[C@@H]2C[C@@]3([C@H]4[C@@]5(CCCC(C)(C)[C@H]5C[C@H]([C@@]4(C1=O)[C@@H]2O)O)CO3)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   348.19 Volume:   350.372
?
Van der Waals volume.
Dense:   0.994 LogP:   2.03
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.324
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.572
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   24.0
TPSA:   86.99
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   3.0 Rings:   5.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.576 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   6.735 Fsp3:   0.85
MCE-18:   129.568
?
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:   0.25 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.029
?
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:   0.173 Promiscuous compounds:   0.322

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.305 MDCK Permeability:   -5.173
Pgp-inhibitor:   0.017 Pgp-substrate:   0.298
PAMPA:   0.591
?
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):   0.021
20% Bioavailability (F20%):   0.282 30% Bioavailability (F30%):   0.622
50% Bioavailability (F50%):   0.963

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.136 MRP1:   0.647
Plasma Protein Binding (PPB):   72.082% Volume Distribution (VD):   -0.06
Fu: 25.768%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.972
OATP1B3 inhibitor:   0.979 BCRP inhibitor:   0.007
BSEP inhibitor:   0.435

ADMET: Metabolism

CYP1A2-inhibitor:   0.003 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.005 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.006 CYP2C9-substrate:   0.006
CYP2D6-inhibitor:   0.023 CYP2D6-substrate:   0.009
CYP3A4-inhibitor:   0.293 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.015
HLM stability:   0.012
?
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):  7.274 Half-life (T1/2):  2.275

ADMET: Toxicity

hERG Blockers:  0.03 hERG Blockers (10um):  0.179
Human Hepatotoxicity (H-HT):  0.686 Drug-induced Liver Injury (DILI):  0.234
AMES Toxicity:  0.847 Rat Oral Acute Toxicity:  0.747
Maximum Recommended Daily Dose:  0.763 Skin Sensitization:  0.992
Carcinogencity:  0.677 Eye Corrosion:  0.003
Eye Irritation:  0.686 Respiratory Toxicity:  0.826
Drug-induced Neurotoxicity:  0.763 Ototoxicity:  0.724
Hematotoxicity:  0.741 Drug-induced Nephrotoxicity:  0.836
Genotoxicity:  0.91 RPMI-8226 Immunitoxicity:  0.212
A549 Cytotoxicity:  0.774 Hek293 Cytotoxicity:  0.771
BCF:   0.66
?
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:   3.236
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.803
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.971
?
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
NPO33194 isodon pseudo-irrorata Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[11858760]

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
NPT1034 Cell line Lu1 Homo sapiens IC50 = 750.0 nM PMID[22182501]
NPT2345 Cell line SW626 Homo sapiens IC50 = 570.0 nM PMID[22182501]
NPT858 Cell line LNCaP Homo sapiens IC50 = 2590.0 nM PMID[22642560]
NPT91 Cell line KB Homo sapiens IC50 = 2590.0 nM PMID[22182501]
NPT307 Cell line HOS Homo sapiens IC50 = 1440.0 nM PMID[19260658]
NPT393 Cell line HCT-116 Homo sapiens Activity = 13.8 % PMID[28337333]
NPT393 Cell line HCT-116 Homo sapiens Activity = 30.2 % PMID[28337333]
NPT393 Cell line HCT-116 Homo sapiens Activity = 33.9 % PMID[28337333]
NPT393 Cell line HCT-116 Homo sapiens Activity = 21.1 % PMID[28337333]
NPT393 Cell line HCT-116 Homo sapiens Activity = 24.7 % PMID[28337333]
NPT393 Cell line HCT-116 Homo sapiens Activity = 26.2 % PMID[28337333]
NPT393 Cell line HCT-116 Homo sapiens Activity = 14.7 % PMID[28337333]
NPT393 Cell line HCT-116 Homo sapiens Activity = 27.8 % PMID[28337333]
NPT393 Cell line HCT-116 Homo sapiens Activity = 18.3 % PMID[28337333]
NPT393 Cell line HCT-116 Homo sapiens Activity = 11.1 % PMID[28337333]
NPT393 Cell line HCT-116 Homo sapiens Activity = 17.0 % PMID[28337333]
NPT393 Cell line HCT-116 Homo sapiens Activity = 10.0 % PMID[28337333]
NPT393 Cell line HCT-116 Homo sapiens Activity = 3.1 % PMID[28337333]
NPT393 Cell line HCT-116 Homo sapiens Activity = 5.3 % PMID[28337333]
NPT393 Cell line HCT-116 Homo sapiens Activity = 8.5 % PMID[28337333]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 4900.0 nM PMID[28337333]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 5900.0 nM PMID[28337333]

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 NPC13149 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
0.5902 Remote Similarity NPC87927
0.5254 Remote Similarity NPC165895
0.5254 Remote Similarity NPC59170
0.5231 Remote Similarity NPC112895
0.5082 Remote Similarity NPC84018

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC13149 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