Natural Product: NPC479998

Natural Product IDNPC479998
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 JOXWHCNNDTWJPX-OLZOCXBDSA-N
IUPAC Name n.a.
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 JOXWHCNNDTWJPX-OLZOCXBDSA-N
Standard InCHI InChI=1S/C23H25NO4/c1-11-7-15-14(5-6-17(25)23(15)20(8-11)28-4)22-16-9-12(2)24-13(3)21(16)18(26)10-19(22)27/h5-8,10,12-13,24-27H,9H2,1-4H3/t12-,13+/m1/s1
SMILES Cc1cc2c(ccc(c2c(c1)OC)O)c1c2C[C@@H](C)N[C@@H](C)c2c(cc1O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   379.18 Volume:   397.204
?
Van der Waals volume.
Dense:   0.955 LogP:   3.53
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.099
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.029
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The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   22.0
TPSA:   81.95
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   4.0 Rings:   4.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.526 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.675 Fsp3:   0.304
MCE-18:   80.0
?
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:   1
Colloidal aggregators:   0.915 Fluc inhibitor:   0.009
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.532
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.198
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.004 Promiscuous compounds:   0.125

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.19 MDCK Permeability:   -4.855
Pgp-inhibitor:   0.002 Pgp-substrate:   1.0
PAMPA:   0.088
?
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):   0.0
20% Bioavailability (F20%):   0.014 30% Bioavailability (F30%):   0.882
50% Bioavailability (F50%):   0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.987
Plasma Protein Binding (PPB):   90.389% Volume Distribution (VD):   0.72
Fu: 9.839%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.236
OATP1B3 inhibitor:   0.021 BCRP inhibitor:   0.012
BSEP inhibitor:   0.946

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.528 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.998 CYP2C9-substrate:   0.998
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.001
CYP3A4-inhibitor:   0.003 CYP3A4-substrate:   0.337
CYP2B6-substrate:   0.344 CYP2C8-inhibitor:   0.005
HLM stability:   0.78
?
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):  1.044 Half-life (T1/2):  1.824

ADMET: Toxicity

hERG Blockers:  0.131 hERG Blockers (10um):  0.554
Human Hepatotoxicity (H-HT):  0.729 Drug-induced Liver Injury (DILI):  0.778
AMES Toxicity:  0.874 Rat Oral Acute Toxicity:  0.721
Maximum Recommended Daily Dose:  0.893 Skin Sensitization:  0.816
Carcinogencity:  0.678 Eye Corrosion:  0.001
Eye Irritation:  0.91 Respiratory Toxicity:  0.98
Drug-induced Neurotoxicity:  0.42 Ototoxicity:  0.631
Hematotoxicity:  0.338 Drug-induced Nephrotoxicity:  0.761
Genotoxicity:  0.688 RPMI-8226 Immunitoxicity:  0.224
A549 Cytotoxicity:  0.814 Hek293 Cytotoxicity:  0.707
BCF:   1.408
?
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:   4.206
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.201
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.899
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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
NPO40017 Ancistrocladus ealaensis Species Ancistrocladaceae Eukaryota n.a. n.a. n.a. PMID[11087584]
NPO40017 Ancistrocladus ealaensis Species Ancistrocladaceae Eukaryota n.a. n.a. n.a. PMID[29560715]
NPO40017 Ancistrocladus ealaensis Species Ancistrocladaceae Eukaryota n.a. n.a. n.a. PMID[31630523]
NPO40017 Ancistrocladus ealaensis Species Ancistrocladaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

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
NPT839 Cell line L6 Rattus norvegicus IC50 = 79100.0 nM PMID[29560715]
NPT844 Organism Trypanosoma brucei rhodesiense Trypanosoma brucei rhodesiense IC50 = 15300.0 nM PMID[29560715]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum IC50 = 12900.0 nM PMID[29560715]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum IC50 = 9940.0 nM PMID[29560715]
NPT633 Organism Leishmania donovani Leishmania donovani IC50 = 26400.0 nM PMID[29560715]
NPT580 Organism Trypanosoma cruzi Trypanosoma cruzi IC50 = 237000.0 nM PMID[29560715]
NPT2 Others Unspecified n.a. Ratio IC50 = 7.95 n.a. PMID[29560715]
NPT2 Others Unspecified n.a. Ratio IC50 = 6.13 n.a. PMID[29560715]

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 NPC479998 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 NPC209377
0.7969 Intermediate Similarity NPC119068
0.7969 Intermediate Similarity NPC40496
0.6986 Remote Similarity NPC257269
0.6522 Remote Similarity NPC479995
0.65 Remote Similarity NPC230276
0.6296 Remote Similarity NPC223236
0.625 Remote Similarity NPC480006
0.593 Remote Similarity NPC259350
0.5811 Remote Similarity NPC221864
0.5753 Remote Similarity NPC480013
0.56 Remote Similarity NPC193853
0.56 Remote Similarity NPC223077
0.56 Remote Similarity NPC44314
0.5172 Remote Similarity NPC479996
0.5172 Remote Similarity NPC90773
0.5065 Remote Similarity NPC480016
0.5063 Remote Similarity NPC96629
0.5059 Remote Similarity NPC480009

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC479998 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
0.7969 Intermediate Similarity NPD8453 Clinical (unspecified phase)

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