Natural Product: NPC202342

Natural Product IDNPC202342
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 DBSKAPJFXJMMFM-SDCGZXQLSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 76320896
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 DBSKAPJFXJMMFM-SDCGZXQLSA-N
Standard InCHI InChI=1S/C22H30O6/c1-11-13-8-14(24)17-21(4)7-5-6-20(3,10-28-12(2)23)15(21)9-16(25)22(17,18(11)26)19(13)27/h13,15-17,19,25,27H,1,5-10H2,2-4H3/t13-,15+,16+,17-,19+,20+,21+,22+/m0/s1
SMILES C=C1[C@@H]2CC(=O)[C@H]3[C@]4(C)CCC[C@](C)(COC(=O)C)[C@H]4C[C@H]([C@@]3(C1=O)[C@@H]2O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   390.2 Volume:   397.038
?
Van der Waals volume.
Dense:   0.983 LogP:   1.747
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.866
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.359
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   23.0
TPSA:   100.9
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.551 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   6.067 Fsp3:   0.773
MCE-18:   110.0
?
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:   0.474 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.039
?
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:   0.173 Promiscuous compounds:   0.496

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.486 MDCK Permeability:   -5.029
Pgp-inhibitor:   0.959 Pgp-substrate:   0.093
PAMPA:   0.955
?
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):   0.589
20% Bioavailability (F20%):   0.416 30% Bioavailability (F30%):   0.923
50% Bioavailability (F50%):   0.956

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.551
Plasma Protein Binding (PPB):   61.84% Volume Distribution (VD):   0.027
Fu: 41.348%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.997 BCRP inhibitor:   0.466
BSEP inhibitor:   0.962

ADMET: Metabolism

CYP1A2-inhibitor:   0.003 CYP1A2-substrate:   0.027
CYP2C19-inhibitor:   0.089 CYP2C19-substrate:   0.081
CYP2C9-inhibitor:   0.008 CYP2C9-substrate:   0.012
CYP2D6-inhibitor:   0.003 CYP2D6-substrate:   0.013
CYP3A4-inhibitor:   0.294 CYP3A4-substrate:   0.661
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.709
HLM stability:   0.646
?
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):  5.194 Half-life (T1/2):  1.522

ADMET: Toxicity

hERG Blockers:  0.008 hERG Blockers (10um):  0.076
Human Hepatotoxicity (H-HT):  0.851 Drug-induced Liver Injury (DILI):  0.921
AMES Toxicity:  0.791 Rat Oral Acute Toxicity:  0.476
Maximum Recommended Daily Dose:  0.725 Skin Sensitization:  0.991
Carcinogencity:  0.947 Eye Corrosion:  0.0
Eye Irritation:  0.421 Respiratory Toxicity:  0.545
Drug-induced Neurotoxicity:  0.163 Ototoxicity:  0.687
Hematotoxicity:  0.942 Drug-induced Nephrotoxicity:  0.984
Genotoxicity:  0.96 RPMI-8226 Immunitoxicity:  0.222
A549 Cytotoxicity:  0.548 Hek293 Cytotoxicity:  0.461
BCF:   0.505
?
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:   3.382
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.239
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.436
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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
NPO24745 Salvia cavaleriei Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[24256484]
NPO24745 Salvia cavaleriei Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24745 Salvia cavaleriei 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
NPT83 Cell line MCF7 Homo sapiens IC50 = 1800.0 nM PMID[24256484]
NPT660 Cell line SW480 Homo sapiens IC50 = 1700.0 nM PMID[24256484]
NPT659 Cell line SMMC-7721 Homo sapiens IC50 = 960.0 nM PMID[24256484]
NPT81 Cell line A549 Homo sapiens IC50 = 940.0 nM PMID[24256484]
NPT116 Cell line HL-60 Homo sapiens IC50 = 710.0 nM PMID[24256484]
NPT27 Others Unspecified n.a. IC50 = 870.0 nM PMID[24256484]

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 NPC202342 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
0.7193 Intermediate Similarity NPC16911
0.7091 Intermediate Similarity NPC64006
0.6721 Remote Similarity NPC309600
0.6721 Remote Similarity NPC305618
0.661 Remote Similarity NPC88203
0.6429 Remote Similarity NPC179399
0.6333 Remote Similarity NPC66479
0.6207 Remote Similarity NPC67178
0.5625 Remote Similarity NPC47853
0.5556 Remote Similarity NPC163963
0.5385 Remote Similarity NPC469982
0.5312 Remote Similarity NPC87927
0.5231 Remote Similarity NPC287676
0.5217 Remote Similarity NPC471038

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC202342 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