Natural Product: NPC584813

Natural Product IDNPC584813
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Perseitol
IUPAC Name (2~{R},3~{R},5~{R},6~{S})-heptane-1,2,3,4,5,6,7-heptol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
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 OXQKEKGBFMQTML-IECVIRLLSA-N
Standard InCHI InChI=1S/C7H16O7/c8-1-3(10)5(12)7(14)6(13)4(11)2-9/h3-14H,1-2H2/t3-,4+,5-,6-,7-/m1/s1
SMILES OC[C@@H](O)[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)CO

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   212.09 Volume:   191.16
?
Van der Waals volume.
Dense:   1.109 LogP:   -1.222
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   -0.91
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -0.641
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   0.0
TPSA:   141.61
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   7.0 Rings:   0.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.236 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.742 Fsp3:   1.0
MCE-18:   5.0
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.017 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.022
?
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:   0.512 Promiscuous compounds:   0.09

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.545 MDCK Permeability:   -4.795
Pgp-inhibitor:   0.0 Pgp-substrate:   0.109
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):   0.004
20% Bioavailability (F20%):   0.002 30% Bioavailability (F30%):   0.006
50% Bioavailability (F50%):   0.668

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.019 MRP1:   0.001
Plasma Protein Binding (PPB):   30.663% Volume Distribution (VD):   -0.463
Fu: 76.244%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.99
OATP1B3 inhibitor:   0.969 BCRP inhibitor:   0.03
BSEP inhibitor:   0.001

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.006
CYP2C9-inhibitor:   0.122 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.907
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):  2.286 Half-life (T1/2):  1.975

ADMET: Toxicity

hERG Blockers:  0.005 hERG Blockers (10um):  0.036
Human Hepatotoxicity (H-HT):  0.231 Drug-induced Liver Injury (DILI):  0.001
AMES Toxicity:  0.37 Rat Oral Acute Toxicity:  0.002
Maximum Recommended Daily Dose:  0.001 Skin Sensitization:  0.41
Carcinogencity:  0.062 Eye Corrosion:  0.0
Eye Irritation:  0.253 Respiratory Toxicity:  0.0
Drug-induced Neurotoxicity:  0.0 Ototoxicity:  0.996
Hematotoxicity:  0.063 Drug-induced Nephrotoxicity:  0.355
Genotoxicity:  0.0 RPMI-8226 Immunitoxicity:  0.039
A549 Cytotoxicity:  0.002 Hek293 Cytotoxicity:  0.006
BCF:   0.07
?
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:   0.927
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   1.58
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   0.904
?
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
NPO16519 Persea americana Species Lauraceae Eukaryota n.a. fruit n.a. PMID[10820058]
NPO16519 Persea americana Species Lauraceae Eukaryota Unripe fruit n.a. n.a. PMID[9644064]
NPO16519 Persea americana Species Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO49126 Persea gratissima Species Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO61401 Persea dymifolia Genus Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18277 Scurrula fusca Species Loranthaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16519 Persea americana Species Lauraceae Eukaryota n.a. n.a. Database[FooDB]
NPO16519 Persea americana Species Lauraceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO16519 Persea americana Species Lauraceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO16519 Persea americana Species Lauraceae Eukaryota n.a. n.a. Database[FooDB]
NPO16519 Persea americana Species Lauraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO16519 Persea americana Species Lauraceae Eukaryota n.a. n.a. Database[Phenol-Explorer]
NPO16519 Persea americana Species Lauraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO16519 Persea americana Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18277 Scurrula fusca Species Loranthaceae 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 NPC584813 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 NPC31981
0.9091 High Similarity NPC293908
0.9091 High Similarity NPC66052
0.9091 High Similarity NPC192065
0.9091 High Similarity NPC86412
0.75 Intermediate Similarity NPC197207
0.75 Intermediate Similarity NPC187058
0.75 Intermediate Similarity NPC182541
0.75 Intermediate Similarity NPC127074
0.75 Intermediate Similarity NPC149070
0.5833 Remote Similarity NPC301586
0.5833 Remote Similarity NPC317060
0.5833 Remote Similarity NPC33415
0.5556 Remote Similarity NPC606151
0.5455 Remote Similarity NPC227707
0.5455 Remote Similarity NPC99573
0.5455 Remote Similarity NPC102981
0.5455 Remote Similarity NPC88278

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC584813 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
0.9091 High Similarity NPD9051 Approved
0.9091 High Similarity NPD9052 Phase 4
0.9091 High Similarity NPD9053 Phase 4
0.75 Intermediate Similarity NPD8814 Phase 3
0.5833 Remote Similarity NPD8549 Clinical (unspecified phase)
0.5556 Remote Similarity NPD9001 Phase 2
0.5556 Remote Similarity NPD9002 Approved
0.5455 Remote Similarity NPD8995 Clinical (unspecified phase)
0.5455 Remote Similarity NPD8996 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