Natural Product: NPC486446

Natural Product IDNPC486446
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 JGKCGXVOATXMRM-LZLXCTOHSA-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:0000279] Alkaloids and derivatives
      • [CHEMONTID:0002750] Corynanthean-type alkaloids

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 JGKCGXVOATXMRM-LZLXCTOHSA-N
Standard InCHI InChI=1S/C21H26N2O3/c1-3-13-11-23-9-8-15-14-6-4-5-7-18(14)22-20(15)19(23)10-16(13)17(12-24)21(25)26-2/h3-7,13,16-17,19,22,24H,1,8-12H2,2H3/t13-,16-,17-,19+/m0/s1
SMILES C=C[C@H]1CN2CCc3c4ccccc4[nH]c3[C@H]2C[C@@H]1[C@H](CO)C(=O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   354.19 Volume:   370.092
?
Van der Waals volume.
Dense:   0.957 LogP:   2.396
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.413
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.267
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   22.0
TPSA:   65.56
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.654 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.088 Fsp3:   0.476
MCE-18:   75.935
?
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:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.205 Fluc inhibitor:   0.007
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.525
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.014
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.003 Promiscuous compounds:   0.551

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.249 MDCK Permeability:   -4.784
Pgp-inhibitor:   0.034 Pgp-substrate:   0.392
PAMPA:   0.095
?
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%):   0.102 30% Bioavailability (F30%):   0.59
50% Bioavailability (F50%):   0.962

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.957 MRP1:   0.864
Plasma Protein Binding (PPB):   70.024% Volume Distribution (VD):   0.145
Fu: 31.973%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.993
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.776
BSEP inhibitor:   0.874

ADMET: Metabolism

CYP1A2-inhibitor:   0.118 CYP1A2-substrate:   0.006
CYP2C19-inhibitor:   0.997 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.588 CYP2C9-substrate:   0.926
CYP2D6-inhibitor:   0.996 CYP2D6-substrate:   0.188
CYP3A4-inhibitor:   0.244 CYP3A4-substrate:   0.24
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.944
HLM stability:   0.208
?
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):  9.751 Half-life (T1/2):  0.951

ADMET: Toxicity

hERG Blockers:  0.334 hERG Blockers (10um):  0.397
Human Hepatotoxicity (H-HT):  0.612 Drug-induced Liver Injury (DILI):  0.169
AMES Toxicity:  0.429 Rat Oral Acute Toxicity:  0.621
Maximum Recommended Daily Dose:  0.897 Skin Sensitization:  0.962
Carcinogencity:  0.641 Eye Corrosion:  0.001
Eye Irritation:  0.679 Respiratory Toxicity:  0.971
Drug-induced Neurotoxicity:  0.873 Ototoxicity:  0.534
Hematotoxicity:  0.064 Drug-induced Nephrotoxicity:  0.567
Genotoxicity:  0.79 RPMI-8226 Immunitoxicity:  0.045
A549 Cytotoxicity:  0.089 Hek293 Cytotoxicity:  0.313
BCF:   0.789
?
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:   3.537
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.263
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.489
?
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
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[10869194]
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota leaves n.a. n.a. PMID[18588343]
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[19331340]
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[27700077]
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[28225280]
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[31789520]
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[31804070]
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO14112 Uncaria rhynchophylla Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO14112 Uncaria rhynchophylla Species Rubiaceae 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
NPT92 Individual protein Serotonin 1a (5-HT1a) receptor Homo sapiens EC50 = 54400.0 nM PMID[31789520]

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 NPC486446 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 NPC486443
0.8194 Intermediate Similarity NPC486452
0.8194 Intermediate Similarity NPC74591
0.7143 Intermediate Similarity NPC273374
0.7051 Intermediate Similarity NPC175474
0.7051 Intermediate Similarity NPC99921
0.6923 Remote Similarity NPC313985
0.6923 Remote Similarity NPC249150
0.6923 Remote Similarity NPC33619
0.6835 Remote Similarity NPC81654
0.64 Remote Similarity NPC229173
0.6296 Remote Similarity NPC486449
0.6296 Remote Similarity NPC63199
0.6296 Remote Similarity NPC111602
0.6296 Remote Similarity NPC102338
0.6296 Remote Similarity NPC196251
0.6071 Remote Similarity NPC312870
0.6071 Remote Similarity NPC199851
0.6071 Remote Similarity NPC294909
0.6071 Remote Similarity NPC254240
0.6071 Remote Similarity NPC128265
0.6071 Remote Similarity NPC604675
0.6024 Remote Similarity NPC107782
0.6024 Remote Similarity NPC486454
0.5974 Remote Similarity NPC185200
0.5714 Remote Similarity NPC317430
0.5641 Remote Similarity NPC21174
0.5625 Remote Similarity NPC165441
0.5521 Remote Similarity NPC191489
0.5402 Remote Similarity NPC131260
0.5366 Remote Similarity NPC482948
0.5349 Remote Similarity NPC483467
0.5294 Remote Similarity NPC220151
0.5294 Remote Similarity NPC19692
0.5287 Remote Similarity NPC50503
0.5287 Remote Similarity NPC607669
0.5248 Remote Similarity NPC486444
0.5248 Remote Similarity NPC649
0.51 Remote Similarity NPC52254
0.51 Remote Similarity NPC611036
0.5067 Remote Similarity NPC88097
0.506 Remote Similarity NPC474897
0.5056 Remote Similarity NPC52557
0.5056 Remote Similarity NPC217463

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC486446 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
0.6923 Remote Similarity NPD4601 Phase 4
0.6835 Remote Similarity NPD4600 Approved
0.6071 Remote Similarity NPD4500 Approved
0.6071 Remote Similarity NPD4501 Approved
0.5521 Remote Similarity NPD7708 Phase 4

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