Natural Product: NPC160844

Natural Product IDNPC160844
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 YRHHFFMCCMEVTR-GBXJYZSASA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 16091459
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0000507] Isoflavonoid O-glycosides

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 YRHHFFMCCMEVTR-GBXJYZSASA-N
Standard InCHI InChI=1S/C21H20O9/c1-9-17(24)19(26)20(27)21(29-9)30-12-6-14(23)16-15(7-12)28-8-13(18(16)25)10-2-4-11(22)5-3-10/h2-9,17,19-24,26-27H,1H3/t9-,17+,19+,20+,21-/m0/s1
SMILES C[C@H]1[C@H]([C@H]([C@H]([C@@H](O1)Oc1cc(c2c(c1)occ(c1ccc(cc1)O)c2=O)O)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   416.11 Volume:   395.567
?
Van der Waals volume.
Dense:   1.052 LogP:   1.049
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.269
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.229
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   24.0
TPSA:   149.82
?
Topological Polar Surface Area.
 H-Bond Acceptor:   9.0
H-Bond Donor:   5.0 Rings:   4.0
Heavy Atoms:   9.0

MedChem Properties

QED Drug-Likeness Score:   0.423 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.832 Fsp3:   0.286
MCE-18:   84.259
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.582 Fluc inhibitor:   0.308
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.945
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.725
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.214 Promiscuous compounds:   0.449

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.16 MDCK Permeability:   -5.197
Pgp-inhibitor:   0.0 Pgp-substrate:   0.84
PAMPA:   0.999
?
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):   0.729
20% Bioavailability (F20%):   0.95 30% Bioavailability (F30%):   0.982
50% Bioavailability (F50%):   0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.568
Plasma Protein Binding (PPB):   88.003% Volume Distribution (VD):   0.061
Fu: 14.424%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.58
OATP1B3 inhibitor:   0.655 BCRP inhibitor:   0.323
BSEP inhibitor:   0.013

ADMET: Metabolism

CYP1A2-inhibitor:   0.806 CYP1A2-substrate:   0.039
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.007
CYP2C9-inhibitor:   0.66 CYP2C9-substrate:   0.213
CYP2D6-inhibitor:   0.089 CYP2D6-substrate:   0.125
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.679
HLM stability:   0.01
?
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):  2.659 Half-life (T1/2):  2.777

ADMET: Toxicity

hERG Blockers:  0.067 hERG Blockers (10um):  0.353
Human Hepatotoxicity (H-HT):  0.621 Drug-induced Liver Injury (DILI):  0.978
AMES Toxicity:  0.889 Rat Oral Acute Toxicity:  0.307
Maximum Recommended Daily Dose:  0.286 Skin Sensitization:  0.982
Carcinogencity:  0.219 Eye Corrosion:  0.0
Eye Irritation:  0.873 Respiratory Toxicity:  0.536
Drug-induced Neurotoxicity:  0.202 Ototoxicity:  0.58
Hematotoxicity:  0.314 Drug-induced Nephrotoxicity:  0.629
Genotoxicity:  0.933 RPMI-8226 Immunitoxicity:  0.18
A549 Cytotoxicity:  0.936 Hek293 Cytotoxicity:  0.692
BCF:   0.912
?
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:   3.638
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.689
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.177
?
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
NPO23838 Kitasatospora kifunensis Species Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[17191679]
NPO23838 Kitasatospora kifunensis Species Streptomycetaceae Bacteria 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 NPC160844 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 NPC348541
0.8676 High Similarity NPC160515
0.8429 Intermediate Similarity NPC197896
0.8429 Intermediate Similarity NPC313163
0.8182 Intermediate Similarity NPC303913
0.7564 Intermediate Similarity NPC487212
0.7534 Intermediate Similarity NPC211014
0.7284 Intermediate Similarity NPC479405
0.7195 Intermediate Similarity NPC479404
0.7067 Intermediate Similarity NPC259070
0.6923 Remote Similarity NPC80140
0.6883 Remote Similarity NPC73511
0.6835 Remote Similarity NPC610187
0.6567 Remote Similarity NPC303644
0.6538 Remote Similarity NPC487213
0.6538 Remote Similarity NPC234739
0.6494 Remote Similarity NPC331652
0.641 Remote Similarity NPC249281
0.641 Remote Similarity NPC108831
0.641 Remote Similarity NPC182634
0.6375 Remote Similarity NPC205076
0.6329 Remote Similarity NPC161749
0.6316 Remote Similarity NPC25547
0.6173 Remote Similarity NPC100720
0.6067 Remote Similarity NPC479403
0.6049 Remote Similarity NPC46420
0.5952 Remote Similarity NPC116458
0.5952 Remote Similarity NPC246943
0.5926 Remote Similarity NPC105511
0.5926 Remote Similarity NPC156457
0.5882 Remote Similarity NPC276377
0.5802 Remote Similarity NPC19709
0.5802 Remote Similarity NPC238376
0.573 Remote Similarity NPC150164
0.5529 Remote Similarity NPC611303
0.5495 Remote Similarity NPC186816
0.5493 Remote Similarity NPC116632
0.5488 Remote Similarity NPC473043
0.5484 Remote Similarity NPC32641
0.5484 Remote Similarity NPC256188
0.5484 Remote Similarity NPC72016
0.5484 Remote Similarity NPC35119
0.5476 Remote Similarity NPC271692
0.5444 Remote Similarity NPC44931
0.5422 Remote Similarity NPC39360
0.5422 Remote Similarity NPC29763
0.5422 Remote Similarity NPC210003
0.5412 Remote Similarity NPC138540
0.5402 Remote Similarity NPC605784
0.5357 Remote Similarity NPC297987
0.5357 Remote Similarity NPC258035
0.5357 Remote Similarity NPC323593
0.5357 Remote Similarity NPC203500
0.5341 Remote Similarity NPC48773
0.5333 Remote Similarity NPC114192
0.5238 Remote Similarity NPC476405
0.5233 Remote Similarity NPC27942
0.5222 Remote Similarity NPC251417
0.5205 Remote Similarity NPC216769
0.52 Remote Similarity NPC90665
0.519 Remote Similarity NPC268668
0.5176 Remote Similarity NPC158674
0.5172 Remote Similarity NPC481043
0.5172 Remote Similarity NPC224462
0.5169 Remote Similarity NPC479407
0.5128 Remote Similarity NPC203636
0.5119 Remote Similarity NPC111929
0.5119 Remote Similarity NPC320283
0.5119 Remote Similarity NPC45165
0.5119 Remote Similarity NPC41121
0.506 Remote Similarity NPC469404
0.5056 Remote Similarity NPC307518
0.5056 Remote Similarity NPC479406
0.5054 Remote Similarity NPC65003

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC160844 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
0.6329 Remote Similarity NPD4381 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