Natural Product: NPC43270

Natural Product IDNPC43270
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 WURVHQYPIFSXKQ-RPUPUWCGSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001551] Diterpenoids
          • [CHEMONTID:0001757] Colensane and clerodane 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 WURVHQYPIFSXKQ-RPUPUWCGSA-N
Standard InCHI InChI=1S/C22H30O5/c1-13-16(7-6-15-9-11-26-12-15)22(5)10-8-17(27-14(2)23)21(3,4)20(22)19(25)18(13)24/h9,11-12,17,19-20,25H,6-8,10H2,1-5H3/t17-,19-,20+,22-/m1/s1
SMILES CC1=C(CCc2ccoc2)[C@@]2(C)CC[C@H](C(C)(C)[C@@H]2[C@@H](C1=O)O)OC(=O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   374.21 Volume:   394.168
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Van der Waals volume.
Dense:   0.949 LogP:   2.762
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.697
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.361
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The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   18.0
TPSA:   76.74
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Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.81 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.318 Fsp3:   0.636
MCE-18:   77.944
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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:   0.634 Fluc inhibitor:   0.005
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.069
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.003
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.063 Promiscuous compounds:   0.05

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.83 MDCK Permeability:   -4.434
Pgp-inhibitor:   0.999 Pgp-substrate:   0.59
PAMPA:   0.403
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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):   0.084
20% Bioavailability (F20%):   0.948 30% Bioavailability (F30%):   0.956
50% Bioavailability (F50%):   0.987

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.973
Plasma Protein Binding (PPB):   95.864% Volume Distribution (VD):   0.247
Fu: 4.793%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.985
OATP1B3 inhibitor:   0.616 BCRP inhibitor:   0.055
BSEP inhibitor:   0.995

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.248
CYP2C19-inhibitor:   0.069 CYP2C19-substrate:   0.017
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.151
CYP2D6-inhibitor:   0.001 CYP2D6-substrate:   0.964
CYP3A4-inhibitor:   0.996 CYP3A4-substrate:   0.999
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.971
?
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):  6.695 Half-life (T1/2):  0.905

ADMET: Toxicity

hERG Blockers:  0.071 hERG Blockers (10um):  0.272
Human Hepatotoxicity (H-HT):  0.392 Drug-induced Liver Injury (DILI):  0.77
AMES Toxicity:  0.579 Rat Oral Acute Toxicity:  0.49
Maximum Recommended Daily Dose:  0.606 Skin Sensitization:  0.716
Carcinogencity:  0.674 Eye Corrosion:  0.021
Eye Irritation:  0.834 Respiratory Toxicity:  0.365
Drug-induced Neurotoxicity:  0.176 Ototoxicity:  0.318
Hematotoxicity:  0.414 Drug-induced Nephrotoxicity:  0.415
Genotoxicity:  0.924 RPMI-8226 Immunitoxicity:  0.075
A549 Cytotoxicity:  0.071 Hek293 Cytotoxicity:  0.21
BCF:   0.984
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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
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.526
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.911
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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
NPO23548 Leonurus heterophyllus Species Lamiaceae Eukaryota Fruits n.a. n.a. PMID[22703163]
NPO23548 Leonurus heterophyllus Species Lamiaceae Eukaryota Fruits n.a. n.a. PMID[24328283]
NPO23548 Leonurus heterophyllus Species Lamiaceae Eukaryota n.a. aerial part n.a. PMID[24704554]
NPO23548 Leonurus heterophyllus Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[32935986]
NPO23548 Leonurus heterophyllus Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23548 Leonurus heterophyllus Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO23548 Leonurus heterophyllus Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO23548 Leonurus heterophyllus 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
NPT113 Cell line RAW264.7 Mus musculus IC50 = 22500.0 nM PMID[32935986]

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 NPC43270 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
0.6885 Remote Similarity NPC483589
0.6721 Remote Similarity NPC176340
0.6613 Remote Similarity NPC25002
0.5652 Remote Similarity NPC483590
0.5493 Remote Similarity NPC488170
0.5147 Remote Similarity NPC483598
0.507 Remote Similarity NPC483594

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC43270 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