Natural Product: NPC605544

Natural Product IDNPC605544
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 ZNHVWPKMFKADKW-ZYBDYUKJSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1435825
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]

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 ZNHVWPKMFKADKW-ZYBDYUKJSA-N
Standard InCHI InChI=1S/C20H32O3/c1-2-3-4-5-10-13-16-19(21)17-14-11-8-6-7-9-12-15-18-20(22)23/h7-11,13-14,17,19,21H,2-6,12,15-16,18H2,1H3,(H,22,23)/b9-7-,11-8-,13-10-,17-14+/t19-/m1/s1
SMILES CCCCC/C=CC[C@@H](O)/C=C/C=CC/C=CCCCC(=O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   320.24 Volume:   367.665
?
Van der Waals volume.
Dense:   0.871 LogP:   5.173
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.223
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.961
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   14.0 Rigid Bonds:   5.0
TPSA:   57.53
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   2.0 Rings:   0.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.263 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.366 Fsp3:   0.55
MCE-18:   2.0
?
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:   0.195 Fluc inhibitor:   0.013
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.005
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.011
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.964 Promiscuous compounds:   0.42

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.148 MDCK Permeability:   -4.969
Pgp-inhibitor:   0.003 Pgp-substrate:   0.011
PAMPA:   0.492
?
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%):   0.128 30% Bioavailability (F30%):   0.388
50% Bioavailability (F50%):   0.702

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.997
Plasma Protein Binding (PPB):   97.549% Volume Distribution (VD):   -0.714
Fu: 1.988%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.005
OATP1B3 inhibitor:   0.098 BCRP inhibitor:   0.031
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.006
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.026 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.127
CYP2B6-substrate:   0.802 CYP2C8-inhibitor:   0.807
HLM stability:   0.023
?
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):  6.93 Half-life (T1/2):  0.574

ADMET: Toxicity

hERG Blockers:  0.183 hERG Blockers (10um):  0.264
Human Hepatotoxicity (H-HT):  0.233 Drug-induced Liver Injury (DILI):  0.0
AMES Toxicity:  0.35 Rat Oral Acute Toxicity:  0.02
Maximum Recommended Daily Dose:  0.517 Skin Sensitization:  1.0
Carcinogencity:  0.047 Eye Corrosion:  0.649
Eye Irritation:  0.978 Respiratory Toxicity:  0.893
Drug-induced Neurotoxicity:  0.007 Ototoxicity:  0.581
Hematotoxicity:  0.007 Drug-induced Nephrotoxicity:  0.381
Genotoxicity:  0.0 RPMI-8226 Immunitoxicity:  0.039
A549 Cytotoxicity:  0.177 Hek293 Cytotoxicity:  0.121
BCF:   0.785
?
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:   3.67
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.984
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.738
?
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
NPO15810 Zea mays Species Poaceae Eukaryota n.a. n.a. n.a. DOI[10.1007/BF00714468]
NPO15810 Zea mays Species Poaceae Eukaryota n.a. n.a. DOI[10.1021/jf00055a023]
NPO15810 Zea mays Species Poaceae Eukaryota n.a. seed n.a. PMID[11539687]
NPO15810 Zea mays Species Poaceae Eukaryota n.a. n.a. n.a. PMID[12713418]
NPO15810 Zea mays Species Poaceae Eukaryota n.a. n.a. n.a. PMID[21080643]
NPO15810 Zea mays Species Poaceae Eukaryota n.a. leaf n.a. PMID[21574561]
NPO15810 Zea mays Species Poaceae Eukaryota n.a. husk n.a. PMID[21574561]
NPO15810 Zea mays Species Poaceae Eukaryota n.a. seed n.a. PMID[23292602]
NPO15810 Zea mays Species Poaceae Eukaryota n.a. n.a. n.a. PMID[29762032]
NPO15810 Zea mays Species Poaceae Eukaryota n.a. pollen n.a. PMID[8987503]
NPO15810 Zea mays Species Poaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8339 Lithothamnion corallioides Species Hapalidiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15810 Zea mays Species Poaceae Eukaryota Silk Stigma Style n.a. n.a. Database[FooDB]
NPO15810 Zea mays Species Poaceae Eukaryota Stem n.a. n.a. Database[FooDB]
NPO15810 Zea mays Species Poaceae Eukaryota Cob n.a. n.a. Database[FooDB]
NPO15810 Zea mays Species Poaceae Eukaryota Silk Essent. Oil n.a. n.a. Database[FooDB]
NPO15810 Zea mays Species Poaceae Eukaryota Shoot n.a. n.a. Database[FooDB]
NPO15810 Zea mays Species Poaceae Eukaryota Seed Essent. Oil n.a. n.a. Database[FooDB]
NPO15810 Zea mays Species Poaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO15810 Zea mays Species Poaceae Eukaryota Root n.a. n.a. Database[FooDB]
NPO15810 Zea mays Species Poaceae Eukaryota Pollen Or Spore n.a. n.a. Database[FooDB]
NPO15810 Zea mays Species Poaceae Eukaryota Plant n.a. n.a. Database[FooDB]
NPO15810 Zea mays Species Poaceae Eukaryota Oil n.a. n.a. Database[FooDB]
NPO15810 Zea mays Species Poaceae Eukaryota Husk Essent. Oil n.a. n.a. Database[FooDB]
NPO15810 Zea mays Species Poaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO15810 Zea mays Species Poaceae Eukaryota n.a. n.a. Database[FooDB]
NPO15810 Zea mays Species Poaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15810 Zea mays Species Poaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15810 Zea mays Species Poaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO15810 Zea mays Species Poaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO8339 Lithothamnion corallioides Species Hapalidiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15810 Zea mays Species Poaceae 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
NPT5 Individual protein Histone-lysine N-methyltransferase, H3 lysine-9 specific 3 Homo sapiens Potency n.a. 3548.1 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT28907 Protein-protein interaction Runt-related transcription factor 1/Core-binding factor subunit beta Homo sapiens Potency n.a. 14125.4 nM PubChem BioAssay data set
NPT605 Organism Homo sapiens Homo sapiens IC50 n.a. n.a. nM PMID[12182849]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT419 Organism Oryctolagus cuniculus Oryctolagus cuniculus IC50 = 4000.0 nM PMID[12182849]





 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 NPC605544 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 NPC607260
0.8 Intermediate Similarity NPC327112
0.7826 Intermediate Similarity NPC323045
0.7826 Intermediate Similarity NPC317881
0.7447 Intermediate Similarity NPC49863
0.6667 Remote Similarity NPC91495
0.6512 Remote Similarity NPC59051
0.6458 Remote Similarity NPC255863
0.6458 Remote Similarity NPC136164
0.6458 Remote Similarity NPC245947
0.6327 Remote Similarity NPC321838
0.6327 Remote Similarity NPC323477
0.6279 Remote Similarity NPC321062
0.6275 Remote Similarity NPC322461
0.6154 Remote Similarity NPC328653
0.6136 Remote Similarity NPC154245
0.6136 Remote Similarity NPC85813
0.6136 Remote Similarity NPC223697
0.6136 Remote Similarity NPC6095
0.6038 Remote Similarity NPC329249
0.5957 Remote Similarity NPC323436
0.5909 Remote Similarity NPC5413
0.5882 Remote Similarity NPC325977
0.5882 Remote Similarity NPC320642
0.5882 Remote Similarity NPC329550
0.58 Remote Similarity NPC243532
0.5769 Remote Similarity NPC328311
0.5625 Remote Similarity NPC322002
0.56 Remote Similarity NPC324475
0.5556 Remote Similarity NPC70387
0.549 Remote Similarity NPC323597
0.549 Remote Similarity NPC211752
0.549 Remote Similarity NPC323498
0.5484 Remote Similarity NPC319021
0.5455 Remote Similarity NPC424
0.5455 Remote Similarity NPC36061
0.5455 Remote Similarity NPC69510
0.5455 Remote Similarity NPC77272
0.5455 Remote Similarity NPC290563
0.5455 Remote Similarity NPC139029
0.5455 Remote Similarity NPC281972
0.5455 Remote Similarity NPC261831
0.5455 Remote Similarity NPC87564
0.5435 Remote Similarity NPC52955
0.5435 Remote Similarity NPC88966
0.5435 Remote Similarity NPC25417
0.5435 Remote Similarity NPC1813
0.5333 Remote Similarity NPC95145
0.5333 Remote Similarity NPC325642
0.5333 Remote Similarity NPC65174
0.5227 Remote Similarity NPC117572
0.5227 Remote Similarity NPC281245
0.5179 Remote Similarity NPC92558
0.5111 Remote Similarity NPC92114
0.5094 Remote Similarity NPC325627

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC605544 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
0.8 Intermediate Similarity NPD4246 Phase 2
0.7447 Intermediate Similarity NPD4247 Clinical (unspecified phase)
0.6136 Remote Similarity NPD4266 Phase 2
0.5909 Remote Similarity NPD3173 Phase 4
0.5686 Remote Similarity NPD39 Phase 4
0.5455 Remote Similarity NPD3195 Phase 2
0.5455 Remote Similarity NPD3196 Approved
0.5435 Remote Similarity NPD3172 Approved
0.5306 Remote Similarity NPD3194 Phase 4
0.5227 Remote Similarity NPD4222 Phase 3

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