Natural Product: NPC65728

Natural Product IDNPC65728
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 MMYRLPYWIWNBNV-RYMSFCIOSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 73603911
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 MMYRLPYWIWNBNV-RYMSFCIOSA-N
Standard InCHI InChI=1S/C22H30O6/c1-9-14-15-16(28-15)17-21(5)7-6-13(27-10(2)23)20(3,4)11(21)8-12(24)22(17,18(9)25)19(14)26/h11-17,19,24,26H,1,6-8H2,2-5H3/t11-,12-,13+,14-,15-,16-,17+,19-,21-,22-/m1/s1
SMILES C=C1[C@@H]2[C@@H]3[C@H]([C@H]4[C@]5(C)CC[C@@H](C(C)(C)[C@H]5C[C@H]([C@@]4(C1=O)[C@@H]2O)O)OC(=O)C)O3

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   390.2 Volume:   391.118
?
Van der Waals volume.
Dense:   0.998 LogP:   1.459
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.856
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.048
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   24.0
TPSA:   96.36
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   2.0 Rings:   5.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.401 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   6.214 Fsp3:   0.818
MCE-18:   129.5
?
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:   0.475 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.047
?
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:   0.189 Promiscuous compounds:   0.58

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.517 MDCK Permeability:   -5.143
Pgp-inhibitor:   0.972 Pgp-substrate:   0.699
PAMPA:   0.67
?
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):   0.208
20% Bioavailability (F20%):   0.975 30% Bioavailability (F30%):   0.993
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.822
Plasma Protein Binding (PPB):   41.383% Volume Distribution (VD):   -0.102
Fu: 61.245%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.952 BCRP inhibitor:   0.072
BSEP inhibitor:   0.945

ADMET: Metabolism

CYP1A2-inhibitor:   0.002 CYP1A2-substrate:   0.002
CYP2C19-inhibitor:   0.006 CYP2C19-substrate:   0.009
CYP2C9-inhibitor:   0.001 CYP2C9-substrate:   0.123
CYP2D6-inhibitor:   0.002 CYP2D6-substrate:   0.019
CYP3A4-inhibitor:   0.043 CYP3A4-substrate:   0.171
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.966
HLM stability:   0.156
?
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):  5.106 Half-life (T1/2):  1.837

ADMET: Toxicity

hERG Blockers:  0.004 hERG Blockers (10um):  0.032
Human Hepatotoxicity (H-HT):  0.585 Drug-induced Liver Injury (DILI):  0.953
AMES Toxicity:  0.956 Rat Oral Acute Toxicity:  0.29
Maximum Recommended Daily Dose:  0.247 Skin Sensitization:  0.999
Carcinogencity:  0.761 Eye Corrosion:  0.003
Eye Irritation:  0.643 Respiratory Toxicity:  0.301
Drug-induced Neurotoxicity:  0.116 Ototoxicity:  0.704
Hematotoxicity:  0.978 Drug-induced Nephrotoxicity:  0.972
Genotoxicity:  0.975 RPMI-8226 Immunitoxicity:  0.261
A549 Cytotoxicity:  0.812 Hek293 Cytotoxicity:  0.588
BCF:   0.487
?
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:   3.227
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.882
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.049
?
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 = 3000.0 nM PMID[24256484]
NPT660 Cell line SW480 Homo sapiens IC50 = 1800.0 nM PMID[24256484]
NPT659 Cell line SMMC-7721 Homo sapiens IC50 = 1300.0 nM PMID[24256484]
NPT81 Cell line A549 Homo sapiens IC50 = 1100.0 nM PMID[24256484]
NPT116 Cell line HL-60 Homo sapiens IC50 = 650.0 nM PMID[24256484]
NPT27 Others Unspecified n.a. IC50 = 730.0 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 NPC65728 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
0.6491 Remote Similarity NPC132813
0.6491 Remote Similarity NPC147965
0.6491 Remote Similarity NPC78427
0.6379 Remote Similarity NPC142716
0.6271 Remote Similarity NPC216114
0.6271 Remote Similarity NPC66479
0.5161 Remote Similarity NPC289148
0.5079 Remote Similarity NPC304832

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC65728 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