Natural Product: NPC122003

Natural Product IDNPC122003
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 UZIHIZDYDJGCPV-GTMDEXKKSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0003642] 8-prenylated flavans
            • [CHEMONTID:0003508] 8-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 UZIHIZDYDJGCPV-GTMDEXKKSA-N
Standard InCHI InChI=1S/C20H20O6/c1-11(10-21)2-4-13-15(22)7-5-14-17(24)9-19(26-20(13)14)12-3-6-16(23)18(25)8-12/h2-3,5-8,19,21-23,25H,4,9-10H2,1H3/b11-2-/t19-/m0/s1
SMILES C/C(=C/Cc1c(ccc2C(=O)C[C@@H](c3ccc(c(c3)O)O)Oc12)O)/CO

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   356.13 Volume:   360.456
?
Van der Waals volume.
Dense:   0.988 LogP:   2.312
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.506
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.11
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   19.0
TPSA:   107.22
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   4.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.496 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.344 Fsp3:   0.25
MCE-18:   60.04
?
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:   1 PAINS Alert:   1
Colloidal aggregators:   0.742 Fluc inhibitor:   0.839
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.343
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.357
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.254 Promiscuous compounds:   0.175

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.058 MDCK Permeability:   -4.765
Pgp-inhibitor:   0.122 Pgp-substrate:   0.005
PAMPA:   0.071
?
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):   0.034
20% Bioavailability (F20%):   0.982 30% Bioavailability (F30%):   0.999
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.82
Plasma Protein Binding (PPB):   93.152% Volume Distribution (VD):   -0.107
Fu: 6.83%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.861
OATP1B3 inhibitor:   0.99 BCRP inhibitor:   0.951
BSEP inhibitor:   0.68

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.446
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.074
CYP2C9-inhibitor:   0.005 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.753
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.689
?
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):  11.394 Half-life (T1/2):  1.517

ADMET: Toxicity

hERG Blockers:  0.066 hERG Blockers (10um):  0.412
Human Hepatotoxicity (H-HT):  0.719 Drug-induced Liver Injury (DILI):  0.752
AMES Toxicity:  0.744 Rat Oral Acute Toxicity:  0.57
Maximum Recommended Daily Dose:  0.657 Skin Sensitization:  0.99
Carcinogencity:  0.422 Eye Corrosion:  0.003
Eye Irritation:  0.976 Respiratory Toxicity:  0.832
Drug-induced Neurotoxicity:  0.252 Ototoxicity:  0.617
Hematotoxicity:  0.084 Drug-induced Nephrotoxicity:  0.41
Genotoxicity:  0.918 RPMI-8226 Immunitoxicity:  0.029
A549 Cytotoxicity:  0.714 Hek293 Cytotoxicity:  0.42
BCF:   1.224
?
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:   3.952
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.394
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.827
?
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
NPO17812 Jatropha neopauciflora Species Euphorbiaceae Eukaryota n.a. n.a. n.a. PMID[17125233]
NPO24286 Micromonospora lupini Species Micromonosporaceae Bacteria n.a. n.a. n.a. PMID[17475486]
NPO21731 Acanthella cavernosa Species Axinellidae Eukaryota n.a. n.a. n.a. PMID[2045823]
NPO24286 Micromonospora lupini Species Micromonosporaceae Bacteria n.a. n.a. n.a. PMID[21226490]
NPO20119 Aconitum sungpanense Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24200 Piper angustifolium Species Piperaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21731 Acanthella cavernosa Species Axinellidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21440 Trixis wrightii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23983 Siphonoglossa buchii n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO24200 Piper angustifolium Species Piperaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20119 Aconitum sungpanense Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20119 Aconitum sungpanense Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24200 Piper angustifolium Species Piperaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO20119 Aconitum sungpanense Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO17812 Jatropha neopauciflora Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23661 Spiraea koreana Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21731 Acanthella cavernosa Species Axinellidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17273 Empedobacter haloabium Species Flavobacteriaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO21430 Myctophum asperum Species Myctophidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23806 Polygala triphylla Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24200 Piper angustifolium Species Piperaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6174 Croton malambo Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4721 Amphiachyris dracunculoides Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23937 Notholaena pallens Species Pteridaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23983 Siphonoglossa buchii n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO24286 Micromonospora lupini Species Micromonosporaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO24420 Aria japonica Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14151 Macaca fascicularis Species Cercopithecidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20119 Aconitum sungpanense Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21440 Trixis wrightii Species Asteraceae 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 NPC122003 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
0.7167 Intermediate Similarity NPC164980
0.7049 Intermediate Similarity NPC150408
0.6935 Remote Similarity NPC149026
0.6774 Remote Similarity NPC236766
0.6429 Remote Similarity NPC477958
0.6377 Remote Similarity NPC479211
0.6324 Remote Similarity NPC36275
0.6286 Remote Similarity NPC479213
0.625 Remote Similarity NPC91560
0.6056 Remote Similarity NPC477957
0.5972 Remote Similarity NPC479215
0.5915 Remote Similarity NPC479214
0.589 Remote Similarity NPC479212
0.5821 Remote Similarity NPC197252
0.5821 Remote Similarity NPC610133
0.5811 Remote Similarity NPC101793
0.5733 Remote Similarity NPC132592
0.5441 Remote Similarity NPC75049
0.541 Remote Similarity NPC103991
0.5362 Remote Similarity NPC66515
0.5294 Remote Similarity NPC107572
0.5294 Remote Similarity NPC32739
0.527 Remote Similarity NPC484416
0.5263 Remote Similarity NPC479217
0.5238 Remote Similarity NPC1612
0.5238 Remote Similarity NPC183959
0.5156 Remote Similarity NPC610021
0.5143 Remote Similarity NPC310130
0.5143 Remote Similarity NPC243171
0.5143 Remote Similarity NPC482705
0.5077 Remote Similarity NPC192083
0.507 Remote Similarity NPC76338
0.507 Remote Similarity NPC250242

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC122003 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
0.5077 Remote Similarity NPD2393 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