Natural Product: NPC33117

Natural Product IDNPC33117
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 FGAAKLDKKBMYCB-AKJGCJRBSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 44257307
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 FGAAKLDKKBMYCB-AKJGCJRBSA-N
Standard InCHI InChI=1S/C22H22O11/c1-30-14-3-2-9(4-12(14)24)11-8-31-15-6-10(5-13(25)17(15)18(11)26)32-22-21(29)20(28)19(27)16(7-23)33-22/h2-6,8,16,19-25,27-29H,7H2,1H3/t16?,19-,20+,21?,22-/m1/s1
SMILES COc1ccc(cc1O)c1coc2cc(cc(c2c1=O)O)O[C@H]1C([C@H]([C@@H](C(CO)O1)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   462.12 Volume:   430.443
?
Van der Waals volume.
Dense:   1.074 LogP:   0.096
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.109
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.248
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   24.0
TPSA:   179.28
?
Topological Polar Surface Area.
 H-Bond Acceptor:   11.0
H-Bond Donor:   6.0 Rings:   4.0
Heavy Atoms:   11.0

MedChem Properties

QED Drug-Likeness Score:   0.302 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.913 Fsp3:   0.318
MCE-18:   86.966
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Accepted
Pfizer Rule:   Rejected GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.595 Fluc inhibitor:   0.192
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.922
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.881
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.096 Promiscuous compounds:   0.225

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.178 MDCK Permeability:   -5.321
Pgp-inhibitor:   0.0 Pgp-substrate:   0.831
PAMPA:   0.995
?
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):   0.965
20% Bioavailability (F20%):   0.736 30% Bioavailability (F30%):   0.996
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.536
Plasma Protein Binding (PPB):   78.41% Volume Distribution (VD):   -0.123
Fu: 21.252%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.93
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.526
BSEP inhibitor:   0.001

ADMET: Metabolism

CYP1A2-inhibitor:   0.101 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.28 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.42
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.56
HLM stability:   0.006
?
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):  2.523 Half-life (T1/2):  3.434

ADMET: Toxicity

hERG Blockers:  0.078 hERG Blockers (10um):  0.293
Human Hepatotoxicity (H-HT):  0.56 Drug-induced Liver Injury (DILI):  0.939
AMES Toxicity:  0.715 Rat Oral Acute Toxicity:  0.148
Maximum Recommended Daily Dose:  0.161 Skin Sensitization:  0.645
Carcinogencity:  0.327 Eye Corrosion:  0.0
Eye Irritation:  0.141 Respiratory Toxicity:  0.088
Drug-induced Neurotoxicity:  0.016 Ototoxicity:  0.903
Hematotoxicity:  0.131 Drug-induced Nephrotoxicity:  0.531
Genotoxicity:  0.534 RPMI-8226 Immunitoxicity:  0.152
A549 Cytotoxicity:  0.205 Hek293 Cytotoxicity:  0.326
BCF:   0.366
?
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:   2.952
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.516
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.612
?
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
NPO24846 Astragalus membranaceus Species Fabaceae Eukaryota n.a. root n.a. DOI[10.1021/np50075a009]
NPO15715 Astragalus mongholicus Species Fabaceae Eukaryota n.a. root n.a. PMID[15763368]
NPO24846 Astragalus membranaceus Species Fabaceae Eukaryota n.a. root n.a. PMID[17253088]
NPO24846 Astragalus membranaceus Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[25068786]
NPO15715 Astragalus mongholicus Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[25844502]
NPO24846 Astragalus membranaceus Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[30758201]
NPO15715 Astragalus mongholicus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24846 Astragalus membranaceus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24846 Astragalus membranaceus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15715 Astragalus mongholicus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15715 Astragalus mongholicus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[MetaboLights]
NPO15715 Astragalus mongholicus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24846 Astragalus membranaceus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24846 Astragalus membranaceus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO15715 Astragalus mongholicus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO15715 Astragalus mongholicus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO24846 Astragalus membranaceus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO15715 Astragalus mongholicus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24846 Astragalus membranaceus Species Fabaceae 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 NPC33117 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
0.8378 Intermediate Similarity NPC73511
0.7949 Intermediate Similarity NPC307518
0.7821 Intermediate Similarity NPC229729
0.7763 Intermediate Similarity NPC197896
0.7763 Intermediate Similarity NPC313163
0.7532 Intermediate Similarity NPC234739
0.7051 Intermediate Similarity NPC160515
0.7037 Intermediate Similarity NPC80140
0.6829 Remote Similarity NPC224462
0.6747 Remote Similarity NPC22832
0.6667 Remote Similarity NPC156457
0.6591 Remote Similarity NPC479405
0.6543 Remote Similarity NPC348541
0.6517 Remote Similarity NPC479404
0.6437 Remote Similarity NPC487212
0.642 Remote Similarity NPC45165
0.6395 Remote Similarity NPC48773
0.6353 Remote Similarity NPC486578
0.631 Remote Similarity NPC205076
0.6235 Remote Similarity NPC285197
0.622 Remote Similarity NPC135345
0.6207 Remote Similarity NPC479407
0.6118 Remote Similarity NPC100720
0.6118 Remote Similarity NPC138540
0.6071 Remote Similarity NPC95090
0.6071 Remote Similarity NPC161749
0.6071 Remote Similarity NPC27408
0.6047 Remote Similarity NPC481043
0.6047 Remote Similarity NPC479402
0.6022 Remote Similarity NPC479403
0.5952 Remote Similarity NPC289667
0.5938 Remote Similarity NPC235575
0.5889 Remote Similarity NPC251417
0.5882 Remote Similarity NPC105511
0.5882 Remote Similarity NPC487213
0.5882 Remote Similarity NPC258035
0.5814 Remote Similarity NPC84362
0.5795 Remote Similarity NPC243930
0.5789 Remote Similarity NPC51326
0.573 Remote Similarity NPC150442
0.573 Remote Similarity NPC311830
0.573 Remote Similarity NPC607201
0.5699 Remote Similarity NPC303913
0.5682 Remote Similarity NPC479401
0.5682 Remote Similarity NPC611303
0.5676 Remote Similarity NPC116632
0.5618 Remote Similarity NPC601607
0.5568 Remote Similarity NPC60966
0.5556 Remote Similarity NPC479406
0.5556 Remote Similarity NPC607707
0.5517 Remote Similarity NPC297987
0.5517 Remote Similarity NPC277205
0.5517 Remote Similarity NPC37919
0.5517 Remote Similarity NPC136042
0.5517 Remote Similarity NPC189142
0.5517 Remote Similarity NPC77660
0.5517 Remote Similarity NPC603782
0.5495 Remote Similarity NPC601586
0.5488 Remote Similarity NPC191154
0.5444 Remote Similarity NPC120099
0.5444 Remote Similarity NPC21666
0.5444 Remote Similarity NPC601144
0.5422 Remote Similarity NPC134819
0.5402 Remote Similarity NPC261866
0.5402 Remote Similarity NPC39360
0.5402 Remote Similarity NPC29763
0.5402 Remote Similarity NPC210003
0.5385 Remote Similarity NPC194653
0.5341 Remote Similarity NPC323593
0.5341 Remote Similarity NPC203500
0.5316 Remote Similarity NPC114192
0.5281 Remote Similarity NPC22195
0.5281 Remote Similarity NPC21190
0.5275 Remote Similarity NPC605067
0.5275 Remote Similarity NPC609478
0.5275 Remote Similarity NPC610187
0.5258 Remote Similarity NPC64425
0.5217 Remote Similarity NPC116458
0.5217 Remote Similarity NPC246943
0.5217 Remote Similarity NPC605784
0.5195 Remote Similarity NPC303644
0.519 Remote Similarity NPC25292
0.5165 Remote Similarity NPC307938
0.5138 Remote Similarity NPC470719
0.5128 Remote Similarity NPC209487
0.5116 Remote Similarity NPC25547
0.5093 Remote Similarity NPC295625
0.5056 Remote Similarity NPC210042
0.5056 Remote Similarity NPC58053
0.5056 Remote Similarity NPC44558
0.5056 Remote Similarity NPC211014
0.5055 Remote Similarity NPC472459
0.5055 Remote Similarity NPC21100

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC33117 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
0.6071 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