Natural Product: NPC75176

Natural Product IDNPC75176
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 SNPYBALVJUBBHC-QQMAYYJASA-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 SNPYBALVJUBBHC-QQMAYYJASA-N
Standard InCHI InChI=1S/C21H22O7/c1-11(10-22)3-5-13-19(27-2)9-17(26)20-16(25)8-18(28-21(13)20)12-4-6-14(23)15(24)7-12/h3-4,6-7,9,18,22-24,26H,5,8,10H2,1-2H3/b11-3-/t18-/m0/s1
SMILES C/C(=C/Cc1c(cc(c2C(=O)C[C@@H](c3ccc(c(c3)O)O)Oc12)O)OC)/CO

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   386.14 Volume:   386.543
?
Van der Waals volume.
Dense:   0.999 LogP:   2.975
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.921
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.448
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   19.0
TPSA:   116.45
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   4.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.461 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.425 Fsp3:   0.286
MCE-18:   62.963
?
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:   0.704 Fluc inhibitor:   0.563
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.421
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.499
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.131 Promiscuous compounds:   0.222

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.071 MDCK Permeability:   -4.775
Pgp-inhibitor:   0.138 Pgp-substrate:   0.015
PAMPA:   0.037
?
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):   0.026
20% Bioavailability (F20%):   0.901 30% Bioavailability (F30%):   0.994
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.003 MRP1:   0.921
Plasma Protein Binding (PPB):   94.397% Volume Distribution (VD):   -0.059
Fu: 5.387%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.981
OATP1B3 inhibitor:   0.994 BCRP inhibitor:   0.963
BSEP inhibitor:   0.489

ADMET: Metabolism

CYP1A2-inhibitor:   0.011 CYP1A2-substrate:   0.017
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.062
CYP2C9-inhibitor:   0.035 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.001 CYP2D6-substrate:   0.624
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.984
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.169
HLM stability:   0.766
?
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):  12.411 Half-life (T1/2):  1.443

ADMET: Toxicity

hERG Blockers:  0.076 hERG Blockers (10um):  0.465
Human Hepatotoxicity (H-HT):  0.742 Drug-induced Liver Injury (DILI):  0.728
AMES Toxicity:  0.732 Rat Oral Acute Toxicity:  0.534
Maximum Recommended Daily Dose:  0.695 Skin Sensitization:  0.994
Carcinogencity:  0.457 Eye Corrosion:  0.001
Eye Irritation:  0.935 Respiratory Toxicity:  0.852
Drug-induced Neurotoxicity:  0.224 Ototoxicity:  0.723
Hematotoxicity:  0.108 Drug-induced Nephrotoxicity:  0.361
Genotoxicity:  0.939 RPMI-8226 Immunitoxicity:  0.041
A549 Cytotoxicity:  0.803 Hek293 Cytotoxicity:  0.449
BCF:   1.339
?
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:   3.954
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.579
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.8
?
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 NPC75176 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
0.7302 Intermediate Similarity NPC220998
0.6119 Remote Similarity NPC156190
0.5571 Remote Similarity NPC610133
0.5455 Remote Similarity NPC261063
0.5395 Remote Similarity NPC213896
0.5385 Remote Similarity NPC321779
0.5303 Remote Similarity NPC321011
0.5303 Remote Similarity NPC294852
0.5303 Remote Similarity NPC188679
0.5278 Remote Similarity NPC76338
0.5278 Remote Similarity NPC250242
0.5263 Remote Similarity NPC328164
0.5211 Remote Similarity NPC175504
0.5211 Remote Similarity NPC148757
0.5205 Remote Similarity NPC291878
0.5139 Remote Similarity NPC480990
0.5075 Remote Similarity NPC192083
0.507 Remote Similarity NPC107572
0.507 Remote Similarity NPC32739
0.5068 Remote Similarity NPC480158
0.5067 Remote Similarity NPC276212
0.5065 Remote Similarity NPC484416

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC75176 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
0.5075 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