Natural Product: NPC200461

Natural Product IDNPC200461
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 DJOJDHGQRNZXQQ-CQSZACIVSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 821416
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 DJOJDHGQRNZXQQ-CQSZACIVSA-N
Standard InCHI InChI=1S/C16H14O5/c1-20-11-6-12(18)16-13(19)8-14(21-15(16)7-11)9-2-4-10(17)5-3-9/h2-7,14,17-18H,8H2,1H3/t14-/m1/s1
SMILES COc1cc(c2C(=O)C[C@H](c3ccc(cc3)O)Oc2c1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   286.08 Volume:   285.119
?
Van der Waals volume.
Dense:   1.003 LogP:   3.041
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.043
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.552
?
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:   0.887 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.737 Fsp3:   0.188
MCE-18:   54.579
?
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:   0.611 Fluc inhibitor:   0.938
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.363
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.324
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.38 Promiscuous compounds:   0.084

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.885 MDCK Permeability:   -4.761
Pgp-inhibitor:   0.996 Pgp-substrate:   0.086
PAMPA:   0.076
?
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%):   0.0 30% Bioavailability (F30%):   0.745
50% Bioavailability (F50%):   0.996

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.69
Plasma Protein Binding (PPB):   95.157% Volume Distribution (VD):   0.05
Fu: 6.067%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   1.0
BSEP inhibitor:   0.988

ADMET: Metabolism

CYP1A2-inhibitor:   0.956 CYP1A2-substrate:   0.989
CYP2C19-inhibitor:   0.031 CYP2C19-substrate:   0.961
CYP2C9-inhibitor:   0.804 CYP2C9-substrate:   0.02
CYP2D6-inhibitor:   0.75 CYP2D6-substrate:   0.947
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.185
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.677
HLM stability:   0.954
?
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):  6.552 Half-life (T1/2):  1.182

ADMET: Toxicity

hERG Blockers:  0.142 hERG Blockers (10um):  0.512
Human Hepatotoxicity (H-HT):  0.701 Drug-induced Liver Injury (DILI):  0.438
AMES Toxicity:  0.706 Rat Oral Acute Toxicity:  0.471
Maximum Recommended Daily Dose:  0.613 Skin Sensitization:  0.631
Carcinogencity:  0.635 Eye Corrosion:  0.021
Eye Irritation:  0.992 Respiratory Toxicity:  0.261
Drug-induced Neurotoxicity:  0.775 Ototoxicity:  0.344
Hematotoxicity:  0.19 Drug-induced Nephrotoxicity:  0.629
Genotoxicity:  0.882 RPMI-8226 Immunitoxicity:  0.128
A549 Cytotoxicity:  0.363 Hek293 Cytotoxicity:  0.62
BCF:   1.227
?
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:   3.779
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.69
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.104
?
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
NPO20738 Piper crassinervium Species Piperaceae Eukaryota n.a. n.a. n.a. PMID[22472691]
NPO19792 Populus tomentosa Species Salicaceae Eukaryota n.a. n.a. n.a. PMID[22860454]
NPO14558 Aquilaria sinensis Species Thymelaeaceae Eukaryota n.a. n.a. n.a. PMID[27128895]
NPO14558 Aquilaria sinensis Species Thymelaeaceae Eukaryota Resinous Wood n.a. n.a. PMID[29227647]
NPO14558 Aquilaria sinensis Species Thymelaeaceae Eukaryota n.a. n.a. n.a. PMID[38792158]
NPO14379 Onobrychis viciifolia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19792 Populus tomentosa Species Salicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20738 Piper crassinervium Species Piperaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14558 Aquilaria sinensis Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14558 Aquilaria sinensis Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19792 Populus tomentosa Species Salicaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20738 Piper crassinervium Species Piperaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14379 Onobrychis viciifolia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20738 Piper crassinervium Species Piperaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14558 Aquilaria sinensis Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO19792 Populus tomentosa Species Salicaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14379 Onobrychis viciifolia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO19792 Populus tomentosa Species Salicaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO14558 Aquilaria sinensis Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO14558 Aquilaria sinensis Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO20738 Piper crassinervium Species Piperaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14558 Aquilaria sinensis Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14379 Onobrychis viciifolia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19792 Populus tomentosa Species Salicaceae 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 NPC200461 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 NPC329203
1.0 High Similarity NPC222342
0.8261 Intermediate Similarity NPC6407
0.8261 Intermediate Similarity NPC545184
0.8085 Intermediate Similarity NPC150648
0.76 Intermediate Similarity NPC310135
0.7551 Intermediate Similarity NPC73028
0.7273 Intermediate Similarity NPC477840
0.7255 Intermediate Similarity NPC18727
0.7143 Intermediate Similarity NPC32441
0.7143 Intermediate Similarity NPC79943
0.7083 Intermediate Similarity NPC140890
0.7059 Intermediate Similarity NPC475267
0.6731 Remote Similarity NPC606248
0.6667 Remote Similarity NPC484336
0.6667 Remote Similarity NPC484337
0.66 Remote Similarity NPC225153
0.66 Remote Similarity NPC479876
0.6538 Remote Similarity NPC274784
0.6538 Remote Similarity NPC20709
0.6538 Remote Similarity NPC324386
0.6415 Remote Similarity NPC469764
0.6379 Remote Similarity NPC470131
0.6379 Remote Similarity NPC470132
0.6296 Remote Similarity NPC602118
0.625 Remote Similarity NPC39351
0.6226 Remote Similarity NPC300668
0.6207 Remote Similarity NPC69674
0.62 Remote Similarity NPC329225
0.62 Remote Similarity NPC147686
0.6111 Remote Similarity NPC176869
0.6111 Remote Similarity NPC3779
0.6111 Remote Similarity NPC210084
0.6 Remote Similarity NPC480158
0.6 Remote Similarity NPC486094
0.5965 Remote Similarity NPC484335
0.5965 Remote Similarity NPC236637
0.5965 Remote Similarity NPC600886
0.5849 Remote Similarity NPC243083
0.5849 Remote Similarity NPC13768
0.5849 Remote Similarity NPC287246
0.5849 Remote Similarity NPC18877
0.5849 Remote Similarity NPC603284
0.5833 Remote Similarity NPC470133
0.5833 Remote Similarity NPC220998
0.5833 Remote Similarity NPC470135
0.5818 Remote Similarity NPC321011
0.5818 Remote Similarity NPC485881
0.5818 Remote Similarity NPC294852
0.5818 Remote Similarity NPC188679
0.5714 Remote Similarity NPC469758
0.5667 Remote Similarity NPC271741
0.566 Remote Similarity NPC188243
0.566 Remote Similarity NPC110228
0.5636 Remote Similarity NPC338131
0.5614 Remote Similarity NPC302950
0.5593 Remote Similarity NPC169591
0.5593 Remote Similarity NPC298223
0.5593 Remote Similarity NPC604412
0.5556 Remote Similarity NPC100099
0.5556 Remote Similarity NPC295261
0.5556 Remote Similarity NPC296490
0.5522 Remote Similarity NPC219163
0.5484 Remote Similarity NPC134171
0.5472 Remote Similarity NPC265871
0.5472 Remote Similarity NPC205093
0.5472 Remote Similarity NPC76465
0.5455 Remote Similarity NPC37392
0.5455 Remote Similarity NPC167624
0.5455 Remote Similarity NPC166482
0.5439 Remote Similarity NPC599987
0.541 Remote Similarity NPC477841
0.5385 Remote Similarity NPC611447
0.537 Remote Similarity NPC476480
0.537 Remote Similarity NPC182421
0.537 Remote Similarity NPC84585
0.5357 Remote Similarity NPC255106
0.5357 Remote Similarity NPC194432
0.5357 Remote Similarity NPC480993
0.5357 Remote Similarity NPC235165
0.5352 Remote Similarity NPC236934
0.5333 Remote Similarity NPC271270
0.5273 Remote Similarity NPC263670
0.5263 Remote Similarity NPC471500
0.5263 Remote Similarity NPC142860
0.5263 Remote Similarity NPC152538
0.5263 Remote Similarity NPC246469
0.5263 Remote Similarity NPC89088
0.5254 Remote Similarity NPC474836
0.5246 Remote Similarity NPC39329
0.5246 Remote Similarity NPC51032
0.5238 Remote Similarity NPC76338
0.5238 Remote Similarity NPC250242
0.5192 Remote Similarity NPC99854
0.5179 Remote Similarity NPC1612
0.5179 Remote Similarity NPC20354
0.5179 Remote Similarity NPC312391
0.5179 Remote Similarity NPC183959
0.5179 Remote Similarity NPC162869
0.5172 Remote Similarity NPC48208
0.5172 Remote Similarity NPC601395
0.5147 Remote Similarity NPC97052
0.5143 Remote Similarity NPC29830
0.5088 Remote Similarity NPC482119
0.5088 Remote Similarity NPC107586
0.5088 Remote Similarity NPC482120
0.5088 Remote Similarity NPC156057
0.5082 Remote Similarity NPC480991
0.5079 Remote Similarity NPC109223
0.5079 Remote Similarity NPC10937
0.5075 Remote Similarity NPC51760
0.5072 Remote Similarity NPC472636

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC200461 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
0.7143 Intermediate Similarity NPD1552 Clinical (unspecified phase)
0.62 Remote Similarity NPD1549 Phase 2
0.5849 Remote Similarity NPD1550 Phase 2
0.5614 Remote Similarity NPD1934 Phase 0

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