Natural Product: NPC485881

Natural Product IDNPC485881
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 VWWMSFMNICMFQB-AWEZNQCLSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 102004642
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0002585] O-methylated flavonoids
          • [CHEMONTID:0002592] 7-O-methylated flavonoids

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 VWWMSFMNICMFQB-AWEZNQCLSA-N
Standard InCHI InChI=1S/C18H18O5/c1-9-16(21)15-13(20)8-14(11-4-6-12(19)7-5-11)23-18(15)10(2)17(9)22-3/h4-7,14,19,21H,8H2,1-3H3/t14-/m0/s1
SMILES Cc1c(c2C(=O)C[C@@H](c3ccc(cc3)O)Oc2c(C)c1OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   314.12 Volume:   319.711
?
Van der Waals volume.
Dense:   0.983 LogP:   3.082
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.887
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.599
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
TPSA:   75.99
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.888 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.02 Fsp3:   0.278
MCE-18:   60.304
?
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:   0.595 Fluc inhibitor:   0.868
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.334
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.333
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.297 Promiscuous compounds:   0.048

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.004 MDCK Permeability:   -4.784
Pgp-inhibitor:   0.714 Pgp-substrate:   0.5
PAMPA:   0.209
?
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%):   0.003 30% Bioavailability (F30%):   0.083
50% Bioavailability (F50%):   0.668

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.003 MRP1:   0.97
Plasma Protein Binding (PPB):   96.297% Volume Distribution (VD):   -0.17
Fu: 3.739%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.137
OATP1B3 inhibitor:   0.736 BCRP inhibitor:   0.926
BSEP inhibitor:   0.883

ADMET: Metabolism

CYP1A2-inhibitor:   0.489 CYP1A2-substrate:   0.178
CYP2C19-inhibitor:   0.002 CYP2C19-substrate:   0.897
CYP2C9-inhibitor:   0.106 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.265 CYP2D6-substrate:   0.095
CYP3A4-inhibitor:   0.115 CYP3A4-substrate:   0.962
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.947
HLM stability:   0.14
?
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):  7.896 Half-life (T1/2):  0.971

ADMET: Toxicity

hERG Blockers:  0.1 hERG Blockers (10um):  0.488
Human Hepatotoxicity (H-HT):  0.793 Drug-induced Liver Injury (DILI):  0.443
AMES Toxicity:  0.575 Rat Oral Acute Toxicity:  0.676
Maximum Recommended Daily Dose:  0.757 Skin Sensitization:  0.904
Carcinogencity:  0.46 Eye Corrosion:  0.13
Eye Irritation:  0.991 Respiratory Toxicity:  0.852
Drug-induced Neurotoxicity:  0.804 Ototoxicity:  0.308
Hematotoxicity:  0.199 Drug-induced Nephrotoxicity:  0.587
Genotoxicity:  0.955 RPMI-8226 Immunitoxicity:  0.134
A549 Cytotoxicity:  0.596 Hek293 Cytotoxicity:  0.59
BCF:   1.276
?
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:   3.991
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.045
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.529
?
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
NPO40939 Syzygium corticosum Species Myrtaceae Eukaryota n.a. n.a. n.a. PMID[30057155]

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
NPT139 Cell line HT-29 Homo sapiens IC50 > 10000.0 nM PMID[30057155]
NPT82 Cell line MDA-MB-231 Homo sapiens IC50 > 10000.0 nM PMID[30057155]
NPT400 Cell line MDA-MB-435 Homo sapiens IC50 = 6000.0 nM PMID[30057155]
NPT377 Cell line OVCAR-3 Homo sapiens IC50 > 10000.0 nM PMID[30057155]

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 NPC485881 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
0.8125 Intermediate Similarity NPC110038
0.7551 Intermediate Similarity NPC167624
0.7551 Intermediate Similarity NPC166482
0.7255 Intermediate Similarity NPC480992
0.6731 Remote Similarity NPC215885
0.6667 Remote Similarity NPC603284
0.6481 Remote Similarity NPC2416
0.6415 Remote Similarity NPC296917
0.6415 Remote Similarity NPC170907
0.6111 Remote Similarity NPC110776
0.6038 Remote Similarity NPC248372
0.6 Remote Similarity NPC192083
0.5849 Remote Similarity NPC225153
0.5849 Remote Similarity NPC479876
0.5818 Remote Similarity NPC194432
0.5818 Remote Similarity NPC329203
0.5818 Remote Similarity NPC324386
0.5818 Remote Similarity NPC222342
0.5714 Remote Similarity NPC480995
0.5714 Remote Similarity NPC475267
0.5714 Remote Similarity NPC477503
0.5714 Remote Similarity NPC606248
0.5614 Remote Similarity NPC271590
0.5593 Remote Similarity NPC270789
0.5574 Remote Similarity NPC265040
0.5484 Remote Similarity NPC470133
0.5484 Remote Similarity NPC220998
0.5455 Remote Similarity NPC32441
0.5455 Remote Similarity NPC79943
0.5439 Remote Similarity NPC324134
0.5439 Remote Similarity NPC476153
0.5439 Remote Similarity NPC40833
0.5323 Remote Similarity NPC69674
0.5273 Remote Similarity NPC213322
0.5263 Remote Similarity NPC300668
0.5263 Remote Similarity NPC480993
0.5246 Remote Similarity NPC480991
0.5238 Remote Similarity NPC470131
0.5238 Remote Similarity NPC470132
0.5185 Remote Similarity NPC329225
0.5185 Remote Similarity NPC147686
0.5172 Remote Similarity NPC469764
0.5172 Remote Similarity NPC210084
0.5167 Remote Similarity NPC231134
0.5161 Remote Similarity NPC107572
0.5161 Remote Similarity NPC32739
0.5156 Remote Similarity NPC486094
0.5156 Remote Similarity NPC76338
0.5156 Remote Similarity NPC250242
0.5152 Remote Similarity NPC473078
0.5088 Remote Similarity NPC134195
0.5088 Remote Similarity NPC177354
0.5079 Remote Similarity NPC3642

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC485881 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
0.6 Remote Similarity NPD2393 Clinical (unspecified phase)
0.5455 Remote Similarity NPD1552 Clinical (unspecified phase)
0.5185 Remote Similarity NPD1549 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