Natural Product: NPC302711

Natural Product IDNPC302711
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 XUSYGBPHQBWGAD-YFCRFVGBSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 6324890
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001283] Terpene lactones
          • [CHEMONTID:0001538] Diterpene lactones

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 XUSYGBPHQBWGAD-YFCRFVGBSA-N
Standard InCHI InChI=1S/C20H26O4/c1-10(2)11-8-12-13-9-14-19(3,4)6-5-7-20(14,18(23)24-13)15(12)17(22)16(11)21/h8,10,13-14,21-22H,5-7,9H2,1-4H3/t13-,14?,20+/m0/s1
SMILES CC(C)c1cc2[C@@H]3CC4C(C)(C)CCC[C@@]4(c2c(c1O)O)C(=O)O3

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   330.18 Volume:   344.865
?
Van der Waals volume.
Dense:   0.957 LogP:   3.133
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.982
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.996
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   20.0
TPSA:   66.76
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   2.0 Rings:   5.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.595 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.256 Fsp3:   0.65
MCE-18:   121.091
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   1
Colloidal aggregators:   0.523 Fluc inhibitor:   0.016
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.23
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.136
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.239 Promiscuous compounds:   0.013

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.852 MDCK Permeability:   -4.753
Pgp-inhibitor:   0.127 Pgp-substrate:   0.029
PAMPA:   0.141
?
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):   0.0
20% Bioavailability (F20%):   0.164 30% Bioavailability (F30%):   0.122
50% Bioavailability (F50%):   0.803

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.103 MRP1:   0.998
Plasma Protein Binding (PPB):   96.141% Volume Distribution (VD):   0.158
Fu: 4.442%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.944
OATP1B3 inhibitor:   0.393 BCRP inhibitor:   0.012
BSEP inhibitor:   0.944

ADMET: Metabolism

CYP1A2-inhibitor:   0.018 CYP1A2-substrate:   0.117
CYP2C19-inhibitor:   0.501 CYP2C19-substrate:   0.894
CYP2C9-inhibitor:   0.109 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.758
CYP3A4-inhibitor:   0.319 CYP3A4-substrate:   0.299
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.725
HLM stability:   0.934
?
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):  11.311 Half-life (T1/2):  1.453

ADMET: Toxicity

hERG Blockers:  0.069 hERG Blockers (10um):  0.549
Human Hepatotoxicity (H-HT):  0.732 Drug-induced Liver Injury (DILI):  0.668
AMES Toxicity:  0.758 Rat Oral Acute Toxicity:  0.895
Maximum Recommended Daily Dose:  0.991 Skin Sensitization:  0.969
Carcinogencity:  0.902 Eye Corrosion:  0.0
Eye Irritation:  0.119 Respiratory Toxicity:  0.87
Drug-induced Neurotoxicity:  0.451 Ototoxicity:  0.661
Hematotoxicity:  0.508 Drug-induced Nephrotoxicity:  0.99
Genotoxicity:  0.97 RPMI-8226 Immunitoxicity:  0.17
A549 Cytotoxicity:  0.635 Hek293 Cytotoxicity:  0.564
BCF:   2.047
?
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:   4.749
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.363
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.922
?
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
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[ 17014425]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. DOI[10.1002/bab.1236]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/j.indcrop.2010.09.006]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. root n.a. PMID[11374966]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[16038550]
NPO25813 Salvia przewalskii Species Lamiaceae Eukaryota n.a. whole plant n.a. PMID[17217287]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[17583950]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[18855446]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[20455578]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[21775156]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[23286284]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[24108414]
NPO12323 Bos taurus Species Bovidae Eukaryota n.a. n.a. n.a. PMID[24211545]
NPO26138 Rosmarinus officinalis Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[26020634]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[27569393]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[29185738]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[30351923]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. root n.a. PMID[3655791]
NPO12323 Bos taurus Species Bovidae Eukaryota Urine n.a. n.a. PMID[6330305]
NPO26138 Rosmarinus officinalis Species Lamiaceae Eukaryota n.a. leaf n.a. PMID[8229021]
NPO12323 Bos taurus Species Bovidae Eukaryota n.a. n.a. n.a. PMID[932730]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota roots n.a. n.a. PMID[9834151]
NPO5178 Pelophylax nigromaculatus Species Ranidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4564 Anguilla japonica Species Anguillidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO913 Pelophylax plancyi Species Ranidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29132 Agaricus campestris Species Agaricaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25813 Salvia przewalskii Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12323 Bos taurus Species Bovidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12323 Bos taurus Species Bovidae Eukaryota n.a. n.a. Database[FooDB]
NPO12323 Bos taurus Species Bovidae Eukaryota n.a. n.a. Database[FooDB]
NPO4564 Anguilla japonica Species Anguillidae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO31339 Rana nigromaculata, Species Ranidae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO31367 Canis familiaris Species Canidae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO26138 Rosmarinus officinalis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO25813 Salvia przewalskii Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO29132 Agaricus campestris Species Agaricaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12323 Bos taurus Species Bovidae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO29132 Agaricus campestris Species Agaricaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5114 Canis lupus familiaris Species Canidae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO4564 Anguilla japonica Species Anguillidae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5178 Pelophylax nigromaculatus Species Ranidae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO26138 Rosmarinus officinalis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO25813 Salvia przewalskii Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO913 Pelophylax plancyi Species Ranidae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12323 Bos taurus Species Bovidae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO29132 Agaricus campestris Species Agaricaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO26138 Rosmarinus officinalis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO12323 Bos taurus Species Bovidae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO26138 Rosmarinus officinalis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4564 Anguilla japonica Species Anguillidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25813 Salvia przewalskii Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO913 Pelophylax plancyi Species Ranidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12323 Bos taurus Species Bovidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29132 Agaricus campestris Species Agaricaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5178 Pelophylax nigromaculatus Species Ranidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5114 Canis lupus familiaris Species Canidae 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

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 NPC302711 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
1.0 High Similarity NPC84786
0.8727 High Similarity NPC487093
0.8571 High Similarity NPC474991
0.6667 Remote Similarity NPC127046
0.6333 Remote Similarity NPC99795
0.5909 Remote Similarity NPC191899
0.5846 Remote Similarity NPC246229
0.5846 Remote Similarity NPC605250
0.5075 Remote Similarity NPC223573

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC302711 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