Natural Product: NPC472505

Natural Product IDNPC472505
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 AQBQBBLJTDSVLC-XHMTVPDMSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3426517
PubChem CID n.a.
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 AQBQBBLJTDSVLC-XHMTVPDMSA-N
Standard InCHI InChI=1S/C22H32O4/c1-13-15-6-7-17-20(3)9-5-10-21(4,19(24)25)16(20)8-11-22(17,12-15)18(13)26-14(2)23/h15-18H,1,5-12H2,2-4H3,(H,24,25)/t15-,16+,17+,18-,20-,21+,22-/m1/s1
SMILES CC(=O)O[C@@H]1C(=C)[C@H]2C[C@]31CC[C@H]1[C@@]([C@@H]3CC2)(C)CCC[C@]1(C)C(=O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   360.23 Volume:   382.094
?
Van der Waals volume.
Dense:   0.943 LogP:   2.691
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.546
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.712
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   22.0
TPSA:   63.6
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.578 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.616 Fsp3:   0.818
MCE-18:   105.0
?
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:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.271 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.016
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.0
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.571 Promiscuous compounds:   0.212

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.62 MDCK Permeability:   -4.73
Pgp-inhibitor:   0.033 Pgp-substrate:   0.004
PAMPA:   0.319
?
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):   0.002
20% Bioavailability (F20%):   0.119 30% Bioavailability (F30%):   0.106
50% Bioavailability (F50%):   0.47

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.027 MRP1:   0.788
Plasma Protein Binding (PPB):   94.046% Volume Distribution (VD):   -0.529
Fu: 6.319%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.387
BSEP inhibitor:   0.884

ADMET: Metabolism

CYP1A2-inhibitor:   0.021 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.241 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.544 CYP3A4-substrate:   0.001
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.01
HLM stability:   0.001
?
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):  2.428 Half-life (T1/2):  1.321

ADMET: Toxicity

hERG Blockers:  0.075 hERG Blockers (10um):  0.121
Human Hepatotoxicity (H-HT):  0.785 Drug-induced Liver Injury (DILI):  0.863
AMES Toxicity:  0.387 Rat Oral Acute Toxicity:  0.333
Maximum Recommended Daily Dose:  0.609 Skin Sensitization:  0.996
Carcinogencity:  0.89 Eye Corrosion:  0.258
Eye Irritation:  0.957 Respiratory Toxicity:  0.871
Drug-induced Neurotoxicity:  0.251 Ototoxicity:  0.396
Hematotoxicity:  0.649 Drug-induced Nephrotoxicity:  0.871
Genotoxicity:  0.672 RPMI-8226 Immunitoxicity:  0.029
A549 Cytotoxicity:  0.148 Hek293 Cytotoxicity:  0.304
BCF:   0.892
?
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:   3.881
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.49
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.873
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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
NPO20739 Jungermannia hyalina Species Jungermanniaceae Eukaryota n.a. Guangxi Zhuang Autonomous Region, China n.a. PMID[25856683]
NPO20739 Jungermannia hyalina Species Jungermanniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20739 Jungermannia hyalina Species Jungermanniaceae 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
NPT82 Cell line MDA-MB-231 Homo sapiens IC50 > 50000.0 nM PMID[15711537]
NPT2410 Cell line NCI-H1299 Homo sapiens IC50 > 50000.0 nM PMID[22850214]
NPT114 Cell line LoVo Homo sapiens IC50 > 50000.0 nM PMID[18676881]
NPT111 Cell line K562 Homo sapiens IC50 > 50000.0 nM PMID[15043407]
NPT90 Cell line DU-145 Homo sapiens IC50 > 50000.0 nM PMID[19453174]
NPT858 Cell line LNCaP Homo sapiens IC50 > 50000.0 nM PMID[18183025]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 50000.0 nM PMID[25856683]

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 NPC472505 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
0.8393 Intermediate Similarity NPC257942
0.6418 Remote Similarity NPC479782
0.5932 Remote Similarity NPC170862
0.5692 Remote Similarity NPC475118
0.5593 Remote Similarity NPC170985
0.5574 Remote Similarity NPC474404
0.5517 Remote Similarity NPC330659
0.5517 Remote Similarity NPC244708
0.5517 Remote Similarity NPC161187
0.55 Remote Similarity NPC212661
0.55 Remote Similarity NPC471035
0.541 Remote Similarity NPC600598
0.5312 Remote Similarity NPC259173
0.5312 Remote Similarity NPC471037
0.5079 Remote Similarity NPC215893

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC472505 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