Natural Product: NPC268736

Natural Product IDNPC268736
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 HITLMPHPGUZLGI-FDBLAFQCSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL485276
PubChem CID 44575984
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 HITLMPHPGUZLGI-FDBLAFQCSA-N
Standard InCHI InChI=1S/C20H30O4/c1-18-7-3-8-19(2,17(23)24)14(18)6-9-20-10-12(4-5-15(18)20)13(11-20)16(21)22/h12-15H,3-11H2,1-2H3,(H,21,22)(H,23,24)/t12-,13-,14+,15+,18-,19-,20+/m1/s1
SMILES C[C@@]12CCC[C@](C)([C@H]1CC[C@]13C[C@@H](CC[C@@H]23)[C@@H](C1)C(=O)O)C(=O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   334.21 Volume:   350.138
?
Van der Waals volume.
Dense:   0.955 LogP:   1.823
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.05
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.806
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   21.0
TPSA:   74.6
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.794 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.512 Fsp3:   0.9
MCE-18:   103.737
?
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:   0.156 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.014
?
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:   0.631 Promiscuous compounds:   0.066

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.695 MDCK Permeability:   -5.047
Pgp-inhibitor:   0.0 Pgp-substrate:   0.009
PAMPA:   1.0
?
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):   0.001
20% Bioavailability (F20%):   0.008 30% Bioavailability (F30%):   0.001
50% Bioavailability (F50%):   0.013

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.003 MRP1:   0.978
Plasma Protein Binding (PPB):   90.958% Volume Distribution (VD):   -0.613
Fu: 11.189%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.984
OATP1B3 inhibitor:   0.643 BCRP inhibitor:   0.001
BSEP inhibitor:   0.451

ADMET: Metabolism

CYP1A2-inhibitor:   0.048 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.006 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.489 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.893 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.0
HLM stability:   0.0
?
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):  1.141 Half-life (T1/2):  1.381

ADMET: Toxicity

hERG Blockers:  0.01 hERG Blockers (10um):  0.004
Human Hepatotoxicity (H-HT):  0.627 Drug-induced Liver Injury (DILI):  0.739
AMES Toxicity:  0.119 Rat Oral Acute Toxicity:  0.087
Maximum Recommended Daily Dose:  0.159 Skin Sensitization:  0.952
Carcinogencity:  0.733 Eye Corrosion:  0.763
Eye Irritation:  0.978 Respiratory Toxicity:  0.868
Drug-induced Neurotoxicity:  0.002 Ototoxicity:  0.63
Hematotoxicity:  0.71 Drug-induced Nephrotoxicity:  0.971
Genotoxicity:  0.219 RPMI-8226 Immunitoxicity:  0.006
A549 Cytotoxicity:  0.004 Hek293 Cytotoxicity:  0.009
BCF:   0.758
?
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:   3.782
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.239
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.323
?
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
NPO2884 Annona squamosa Species Annonaceae Eukaryota seeds n.a. n.a. PMID[11141125]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. n.a. n.a. PMID[12398544]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. n.a. n.a. PMID[18419154]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. n.a. n.a. PMID[19296389]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. n.a. n.a. PMID[21910504]
NPO2884 Annona squamosa Species Annonaceae Eukaryota seeds n.a. n.a. PMID[22011319]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. seed n.a. PMID[22011319]
NPO2884 Annona squamosa Species Annonaceae Eukaryota Barks n.a. n.a. PMID[2348205]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. fruit n.a. PMID[8786370]
NPO2884 Annona squamosa Species Annonaceae Eukaryota bark n.a. n.a. PMID[9214729]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2884 Annona squamosa Species Annonaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. n.a. Database[FooDB]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO2884 Annona squamosa Species Annonaceae 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
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 15.4 % PMID[12398544]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 56.9 % PMID[12398544]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 15.2 % PMID[12398544]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 6.0 % PMID[12398544]

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 NPC268736 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 NPC477931
0.6531 Remote Similarity NPC480087
0.6531 Remote Similarity NPC480088
0.6471 Remote Similarity NPC252032
0.6471 Remote Similarity NPC319671
0.6471 Remote Similarity NPC476734
0.64 Remote Similarity NPC469941
0.6275 Remote Similarity NPC330659
0.6275 Remote Similarity NPC244708
0.6275 Remote Similarity NPC161187
0.6154 Remote Similarity NPC64466
0.6154 Remote Similarity NPC196197
0.6154 Remote Similarity NPC480091
0.5818 Remote Similarity NPC180199
0.5818 Remote Similarity NPC477919
0.5714 Remote Similarity NPC480094
0.5686 Remote Similarity NPC130459
0.5686 Remote Similarity NPC474221
0.5517 Remote Similarity NPC469940
0.5517 Remote Similarity NPC480090
0.5455 Remote Similarity NPC170985
0.5455 Remote Similarity NPC486673
0.5439 Remote Similarity NPC607026
0.541 Remote Similarity NPC480086
0.5357 Remote Similarity NPC486677
0.5357 Remote Similarity NPC477930
0.5312 Remote Similarity NPC609700
0.5179 Remote Similarity NPC248758
0.5172 Remote Similarity NPC215893
0.5088 Remote Similarity NPC212661
0.5088 Remote Similarity NPC471035

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC268736 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
0.5741 Remote Similarity NPD4224 Phase 2

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