Natural Product: NPC69674

Natural Product IDNPC69674
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 PMQBKFKEJGCJIK-KRWDZBQOSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 15485967
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0003646] 6-prenylated flavans
            • [CHEMONTID:0003507] 6-prenylated flavanones

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 PMQBKFKEJGCJIK-KRWDZBQOSA-N
Standard InCHI InChI=1S/C21H22O5/c1-12(2)4-9-15-18(25-3)11-19-20(21(15)24)16(23)10-17(26-19)13-5-7-14(22)8-6-13/h4-8,11,17,22,24H,9-10H2,1-3H3/t17-/m0/s1
SMILES CC(=CCc1c(cc2c(C(=O)C[C@@H](c3ccc(cc3)O)O2)c1O)OC)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   354.15 Volume:   368.962
?
Van der Waals volume.
Dense:   0.96 LogP:   4.351
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.596
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.156
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   19.0
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:   0.8 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.122 Fsp3:   0.286
MCE-18:   59.815
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.778 Fluc inhibitor:   0.862
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.5
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.437
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.296 Promiscuous compounds:   0.097

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.896 MDCK Permeability:   -4.761
Pgp-inhibitor:   0.999 Pgp-substrate:   0.06
PAMPA:   0.137
?
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):   0.001
20% Bioavailability (F20%):   0.005 30% Bioavailability (F30%):   0.966
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.919
Plasma Protein Binding (PPB):   96.673% Volume Distribution (VD):   0.155
Fu: 2.816%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.997
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   1.0
BSEP inhibitor:   0.994

ADMET: Metabolism

CYP1A2-inhibitor:   0.159 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.956 CYP2C19-substrate:   0.999
CYP2C9-inhibitor:   0.049 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.267 CYP2D6-substrate:   0.98
CYP3A4-inhibitor:   0.175 CYP3A4-substrate:   0.998
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.998
HLM stability:   1.0
?
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):  6.457 Half-life (T1/2):  1.205

ADMET: Toxicity

hERG Blockers:  0.09 hERG Blockers (10um):  0.494
Human Hepatotoxicity (H-HT):  0.752 Drug-induced Liver Injury (DILI):  0.298
AMES Toxicity:  0.723 Rat Oral Acute Toxicity:  0.728
Maximum Recommended Daily Dose:  0.641 Skin Sensitization:  0.902
Carcinogencity:  0.573 Eye Corrosion:  0.001
Eye Irritation:  0.948 Respiratory Toxicity:  0.365
Drug-induced Neurotoxicity:  0.873 Ototoxicity:  0.518
Hematotoxicity:  0.226 Drug-induced Nephrotoxicity:  0.806
Genotoxicity:  0.952 RPMI-8226 Immunitoxicity:  0.114
A549 Cytotoxicity:  0.444 Hek293 Cytotoxicity:  0.646
BCF:   1.73
?
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:   4.526
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.997
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.376
?
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
NPO40372 Tephrosia linearis Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[32155073]
NPO40372 Tephrosia linearis Species Fabaceae 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
NPT927 Cell line PBMC Homo sapiens Activity = 102.34 % PMID[32155073]
NPT927 Cell line PBMC Homo sapiens Activity = 57.64 % PMID[32155073]
NPT927 Cell line PBMC Homo sapiens Activity = 19.57 % PMID[32155073]
NPT927 Cell line PBMC Homo sapiens Activity = 46.89 % PMID[32155073]
NPT927 Cell line PBMC Homo sapiens Activity = 6.38 % PMID[32155073]
NPT22689 Protein complex Programmed cell death protein 1/Programmed cell death 1 ligand 1 Homo sapiens IC50 = 96600.0 nM PMID[32667799]

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 NPC69674 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
0.7333 Intermediate Similarity NPC486094
0.6949 Remote Similarity NPC169591
0.6949 Remote Similarity NPC298223
0.6949 Remote Similarity NPC604412
0.6721 Remote Similarity NPC265040
0.6613 Remote Similarity NPC220998
0.6557 Remote Similarity NPC107572
0.6557 Remote Similarity NPC32739
0.6508 Remote Similarity NPC76338
0.6508 Remote Similarity NPC250242
0.6471 Remote Similarity NPC472636
0.6269 Remote Similarity NPC246948
0.6212 Remote Similarity NPC473078
0.6207 Remote Similarity NPC329203
0.6207 Remote Similarity NPC222342
0.619 Remote Similarity NPC75049
0.6143 Remote Similarity NPC299436
0.6129 Remote Similarity NPC164980
0.6102 Remote Similarity NPC475267
0.6066 Remote Similarity NPC41461
0.6056 Remote Similarity NPC201800
0.6032 Remote Similarity NPC39329
0.6032 Remote Similarity NPC51032
0.5942 Remote Similarity NPC228504
0.5882 Remote Similarity NPC35038
0.5846 Remote Similarity NPC470131
0.5846 Remote Similarity NPC470132
0.5781 Remote Similarity NPC1089
0.5758 Remote Similarity NPC125855
0.5758 Remote Similarity NPC223500
0.5692 Remote Similarity NPC148757
0.5692 Remote Similarity NPC250214
0.5667 Remote Similarity NPC324386
0.5634 Remote Similarity NPC488553
0.5625 Remote Similarity NPC143896
0.5606 Remote Similarity NPC109223
0.5606 Remote Similarity NPC68104
0.5606 Remote Similarity NPC10937
0.5606 Remote Similarity NPC610133
0.5588 Remote Similarity NPC161506
0.5574 Remote Similarity NPC469764
0.5574 Remote Similarity NPC606248
0.5571 Remote Similarity NPC166934
0.5571 Remote Similarity NPC142405
0.5556 Remote Similarity NPC488556
0.5541 Remote Similarity NPC472628
0.5479 Remote Similarity NPC472627
0.5455 Remote Similarity NPC221432
0.5455 Remote Similarity NPC149026
0.5455 Remote Similarity NPC95936
0.5455 Remote Similarity NPC257097
0.5455 Remote Similarity NPC482758
0.5441 Remote Similarity NPC608140
0.5424 Remote Similarity NPC225153
0.5424 Remote Similarity NPC479876
0.5417 Remote Similarity NPC472629
0.541 Remote Similarity NPC300668
0.5395 Remote Similarity NPC472624
0.5385 Remote Similarity NPC76372
0.5385 Remote Similarity NPC37496
0.5385 Remote Similarity NPC258630
0.5373 Remote Similarity NPC17170
0.5373 Remote Similarity NPC66515
0.5373 Remote Similarity NPC310130
0.5333 Remote Similarity NPC119209
0.5333 Remote Similarity NPC32441
0.5333 Remote Similarity NPC79943
0.5325 Remote Similarity NPC472632
0.5323 Remote Similarity NPC485881
0.5323 Remote Similarity NPC210084
0.5303 Remote Similarity NPC324436
0.5303 Remote Similarity NPC78
0.5294 Remote Similarity NPC285555
0.5286 Remote Similarity NPC291508
0.5224 Remote Similarity NPC187282
0.5217 Remote Similarity NPC291878
0.5211 Remote Similarity NPC36275
0.5205 Remote Similarity NPC64915
0.52 Remote Similarity NPC192686
0.52 Remote Similarity NPC284820
0.5161 Remote Similarity NPC480993
0.5147 Remote Similarity NPC480990
0.5147 Remote Similarity NPC197252
0.5143 Remote Similarity NPC470647
0.5135 Remote Similarity NPC214774
0.5135 Remote Similarity NPC479215
0.5132 Remote Similarity NPC312273
0.5085 Remote Similarity NPC329225
0.5085 Remote Similarity NPC147686
0.5082 Remote Similarity NPC98115
0.5082 Remote Similarity NPC6407
0.5082 Remote Similarity NPC545184
0.5077 Remote Similarity NPC66349
0.5077 Remote Similarity NPC168105
0.5075 Remote Similarity NPC236766
0.5075 Remote Similarity NPC150408
0.507 Remote Similarity NPC200761
0.5067 Remote Similarity NPC185276
0.5065 Remote Similarity NPC195796
0.5065 Remote Similarity NPC488550

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC69674 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
0.5333 Remote Similarity NPD1552 Clinical (unspecified phase)
0.5085 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