Natural Product: NPC13787

Natural Product IDNPC13787
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 SDHTXBWLVGWJFT-ATGZISJRSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 457846
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 SDHTXBWLVGWJFT-ATGZISJRSA-N
Standard InCHI InChI=1S/C20H28O6/c1-9-10-4-5-11-18-8-26-20(25,19(11,14(9)22)15(10)23)16(24)13(18)17(2,3)7-6-12(18)21/h10-13,15-16,21,23-25H,1,4-8H2,2-3H3/t10?,11?,12-,13+,15-,16-,18?,19?,20+/m0/s1
SMILES C=C1C2CCC3C45CO[C@]([C@H]([C@@H]5C(C)(C)CC[C@@H]4O)O)(C3(C1=O)[C@H]2O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   364.19 Volume:   359.162
?
Van der Waals volume.
Dense:   1.014 LogP:   1.534
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.919
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.135
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   24.0
TPSA:   107.22
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   4.0 Rings:   6.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.463 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   6.856 Fsp3:   0.85
MCE-18:   133.378
?
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:   0.068 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.032
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.006
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.137 Promiscuous compounds:   0.038

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.143 MDCK Permeability:   -4.808
Pgp-inhibitor:   0.016 Pgp-substrate:   0.819
PAMPA:   0.987
?
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):   0.661
20% Bioavailability (F20%):   0.404 30% Bioavailability (F30%):   0.885
50% Bioavailability (F50%):   0.994

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.012 MRP1:   0.874
Plasma Protein Binding (PPB):   45.641% Volume Distribution (VD):   -0.242
Fu: 55.855%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.987
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.017
BSEP inhibitor:   0.156

ADMET: Metabolism

CYP1A2-inhibitor:   0.006 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.004 CYP2C19-substrate:   0.005
CYP2C9-inhibitor:   0.062 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.003 CYP2D6-substrate:   0.028
CYP3A4-inhibitor:   0.015 CYP3A4-substrate:   0.006
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.003
HLM stability:   0.162
?
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):  3.631 Half-life (T1/2):  2.555

ADMET: Toxicity

hERG Blockers:  0.061 hERG Blockers (10um):  0.278
Human Hepatotoxicity (H-HT):  0.635 Drug-induced Liver Injury (DILI):  0.224
AMES Toxicity:  0.761 Rat Oral Acute Toxicity:  0.703
Maximum Recommended Daily Dose:  0.803 Skin Sensitization:  0.92
Carcinogencity:  0.624 Eye Corrosion:  0.0
Eye Irritation:  0.136 Respiratory Toxicity:  0.71
Drug-induced Neurotoxicity:  0.366 Ototoxicity:  0.82
Hematotoxicity:  0.229 Drug-induced Nephrotoxicity:  0.321
Genotoxicity:  0.812 RPMI-8226 Immunitoxicity:  0.231
A549 Cytotoxicity:  0.22 Hek293 Cytotoxicity:  0.74
BCF:   0.469
?
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:   3.176
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.818
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.866
?
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
NPO26542 Rubia cordifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/S0168-1656(02)00067-6]
NPO26542 Rubia cordifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[18078747]
NPO28626 Isodon rubescens Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[25590529]
NPO26542 Rubia cordifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[8882438]
NPO28626 Isodon rubescens Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26542 Rubia cordifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26542 Rubia cordifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO26542 Rubia cordifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28626 Isodon rubescens Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO26542 Rubia cordifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO28626 Isodon rubescens Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO26542 Rubia cordifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO28626 Isodon rubescens Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26542 Rubia cordifolia Species Rubiaceae 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 NPC13787 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 NPC55973
1.0 High Similarity NPC89860
1.0 High Similarity NPC189663
1.0 High Similarity NPC153234
0.8302 Intermediate Similarity NPC488144
0.8302 Intermediate Similarity NPC483202
0.7719 Intermediate Similarity NPC488142
0.7719 Intermediate Similarity NPC213320
0.6897 Remote Similarity NPC488145
0.6842 Remote Similarity NPC475803
0.6724 Remote Similarity NPC130511
0.6724 Remote Similarity NPC307660
0.6667 Remote Similarity NPC488143
0.6552 Remote Similarity NPC471461
0.6441 Remote Similarity NPC471476
0.6441 Remote Similarity NPC473324
0.6393 Remote Similarity NPC471244
0.6393 Remote Similarity NPC471093
0.6379 Remote Similarity NPC30477
0.6333 Remote Similarity NPC63244
0.6333 Remote Similarity NPC122339
0.6094 Remote Similarity NPC488148
0.6094 Remote Similarity NPC471245
0.6032 Remote Similarity NPC102741
0.5833 Remote Similarity NPC473352
0.5738 Remote Similarity NPC309388
0.5625 Remote Similarity NPC473397
0.5606 Remote Similarity NPC474927
0.5574 Remote Similarity NPC252679
0.5574 Remote Similarity NPC118721
0.5556 Remote Similarity NPC483201
0.5556 Remote Similarity NPC477352
0.5323 Remote Similarity NPC473348
0.5303 Remote Similarity NPC145625
0.5231 Remote Similarity NPC488156
0.5231 Remote Similarity NPC321423
0.5231 Remote Similarity NPC488155
0.5224 Remote Similarity NPC473410
0.5224 Remote Similarity NPC471094
0.5224 Remote Similarity NPC469984
0.5152 Remote Similarity NPC483203
0.5147 Remote Similarity NPC88945
0.5079 Remote Similarity NPC52899
0.5079 Remote Similarity NPC327247
0.5075 Remote Similarity NPC132668

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC13787 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