Natural Product: NPC3071

Natural Product IDNPC3071
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 IPEHJNRNYPOFII-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 275529
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001551] 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 IPEHJNRNYPOFII-UHFFFAOYSA-N
Standard InCHI InChI=1S/C20H28O2/c1-12(2)13-9-14-15(10-16(13)21)20(5)8-6-7-19(3,4)18(20)11-17(14)22/h9-10,12,18,21H,6-8,11H2,1-5H3
SMILES CC(C)c1cc2c(cc1O)C1(C)CCCC(C)(C)C1CC2=O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   300.21 Volume:   335.841
?
Van der Waals volume.
Dense:   0.894 LogP:   4.165
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.644
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.56
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   17.0
TPSA:   37.3
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.775 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.536 Fsp3:   0.65
MCE-18:   75.333
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.191 Fluc inhibitor:   0.025
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.201
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.065
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.526 Promiscuous compounds:   0.03

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.662 MDCK Permeability:   -4.871
Pgp-inhibitor:   0.815 Pgp-substrate:   0.001
PAMPA:   0.038
?
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):   0.003
20% Bioavailability (F20%):   0.062 30% Bioavailability (F30%):   0.565
50% Bioavailability (F50%):   0.995

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.07 MRP1:   0.971
Plasma Protein Binding (PPB):   98.141% Volume Distribution (VD):   0.812
Fu: 3.006%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.935
OATP1B3 inhibitor:   0.995 BCRP inhibitor:   0.042
BSEP inhibitor:   0.982

ADMET: Metabolism

CYP1A2-inhibitor:   0.156 CYP1A2-substrate:   0.67
CYP2C19-inhibitor:   0.835 CYP2C19-substrate:   0.298
CYP2C9-inhibitor:   0.969 CYP2C9-substrate:   0.186
CYP2D6-inhibitor:   0.754 CYP2D6-substrate:   0.092
CYP3A4-inhibitor:   0.01 CYP3A4-substrate:   0.394
CYP2B6-substrate:   0.672 CYP2C8-inhibitor:   0.666
HLM stability:   0.991
?
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):  8.492 Half-life (T1/2):  0.633

ADMET: Toxicity

hERG Blockers:  0.124 hERG Blockers (10um):  0.728
Human Hepatotoxicity (H-HT):  0.49 Drug-induced Liver Injury (DILI):  0.266
AMES Toxicity:  0.246 Rat Oral Acute Toxicity:  0.393
Maximum Recommended Daily Dose:  0.894 Skin Sensitization:  0.761
Carcinogencity:  0.354 Eye Corrosion:  0.073
Eye Irritation:  0.934 Respiratory Toxicity:  0.921
Drug-induced Neurotoxicity:  0.439 Ototoxicity:  0.837
Hematotoxicity:  0.416 Drug-induced Nephrotoxicity:  0.375
Genotoxicity:  0.025 RPMI-8226 Immunitoxicity:  0.089
A549 Cytotoxicity:  0.632 Hek293 Cytotoxicity:  0.484
BCF:   2.44
?
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:   4.943
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.458
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.189
?
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]
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]
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]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota roots n.a. n.a. PMID[9834151]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5743 Salvia miltiorrhiza Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5743 Salvia miltiorrhiza Species Lamiaceae 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]
NPO5743 Salvia miltiorrhiza 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

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 NPC3071 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 NPC176130
0.8431 Intermediate Similarity NPC471851
0.8367 Intermediate Similarity NPC606689
0.78 Intermediate Similarity NPC69424
0.7647 Intermediate Similarity NPC303910
0.7 Intermediate Similarity NPC605496
0.6792 Remote Similarity NPC111845
0.6727 Remote Similarity NPC36765
0.6607 Remote Similarity NPC605657
0.6545 Remote Similarity NPC78364
0.6538 Remote Similarity NPC219573
0.6429 Remote Similarity NPC78307
0.6364 Remote Similarity NPC164295
0.6207 Remote Similarity NPC309169
0.6111 Remote Similarity NPC260323
0.6071 Remote Similarity NPC80443
0.6034 Remote Similarity NPC471853
0.6034 Remote Similarity NPC478653
0.5932 Remote Similarity NPC196941
0.5893 Remote Similarity NPC471671
0.5833 Remote Similarity NPC481087
0.5818 Remote Similarity NPC176279
0.5781 Remote Similarity NPC100242
0.5614 Remote Similarity NPC3009
0.5614 Remote Similarity NPC84672
0.5517 Remote Similarity NPC11250
0.55 Remote Similarity NPC478646
0.5424 Remote Similarity NPC137750
0.5424 Remote Similarity NPC604431
0.5397 Remote Similarity NPC603203
0.5254 Remote Similarity NPC265513
0.5172 Remote Similarity NPC92079
0.5167 Remote Similarity NPC108129
0.5161 Remote Similarity NPC58560
0.5156 Remote Similarity NPC5568
0.5085 Remote Similarity NPC72667
0.5085 Remote Similarity NPC38893
0.5085 Remote Similarity NPC250323

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC3071 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