Natural Product: NPC486449

Natural Product IDNPC486449
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 NMLUOJBSAYAYEM-ATFUNYTMSA-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]

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 NMLUOJBSAYAYEM-ATFUNYTMSA-N
Standard InCHI InChI=1S/C22H28N2O3/c1-4-14-12-24-10-9-16-15-7-5-6-8-19(15)23-21(16)20(24)11-17(14)18(13-26-2)22(25)27-3/h5-8,13-14,17,20,23H,4,9-12H2,1-3H3/b18-13+/t14-,17+,20+/m0/s1
SMILES CC[C@H]1CN2CCc3c4ccccc4[nH]c3[C@H]2C[C@H]1/C(=COC)/C(=O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   368.21 Volume:   387.388
?
Van der Waals volume.
Dense:   0.95 LogP:   3.916
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.457
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.386
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   22.0
TPSA:   54.56
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.506 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.859 Fsp3:   0.5
MCE-18:   75.333
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.246 Fluc inhibitor:   0.276
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.614
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.287
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.002 Promiscuous compounds:   0.578

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.956 MDCK Permeability:   -4.853
Pgp-inhibitor:   0.267 Pgp-substrate:   0.288
PAMPA:   0.074
?
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%):   0.063 30% Bioavailability (F30%):   0.338
50% Bioavailability (F50%):   0.974

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.962 MRP1:   0.981
Plasma Protein Binding (PPB):   86.38% Volume Distribution (VD):   0.39
Fu: 13.7%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.925
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.994 CYP1A2-substrate:   0.002
CYP2C19-inhibitor:   0.954 CYP2C19-substrate:   0.007
CYP2C9-inhibitor:   0.003 CYP2C9-substrate:   0.994
CYP2D6-inhibitor:   0.99 CYP2D6-substrate:   0.66
CYP3A4-inhibitor:   0.996 CYP3A4-substrate:   0.089
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.208
HLM stability:   0.05
?
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):  8.125 Half-life (T1/2):  0.521

ADMET: Toxicity

hERG Blockers:  0.428 hERG Blockers (10um):  0.647
Human Hepatotoxicity (H-HT):  0.824 Drug-induced Liver Injury (DILI):  0.824
AMES Toxicity:  0.751 Rat Oral Acute Toxicity:  0.758
Maximum Recommended Daily Dose:  0.993 Skin Sensitization:  0.996
Carcinogencity:  0.906 Eye Corrosion:  0.0
Eye Irritation:  0.05 Respiratory Toxicity:  0.996
Drug-induced Neurotoxicity:  0.62 Ototoxicity:  0.62
Hematotoxicity:  0.134 Drug-induced Nephrotoxicity:  0.856
Genotoxicity:  0.773 RPMI-8226 Immunitoxicity:  0.253
A549 Cytotoxicity:  0.44 Hek293 Cytotoxicity:  0.772
BCF:   1.669
?
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:   4.207
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.672
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.189
?
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 > 100000.0 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
NPT29 Organism Rattus norvegicus Rattus norvegicus IC50 = 180.0 nM PMID[33148492]





 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 NPC486449 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 NPC63199
1.0 High Similarity NPC111602
1.0 High Similarity NPC102338
1.0 High Similarity NPC196251
0.8333 Intermediate Similarity NPC273374
0.7763 Intermediate Similarity NPC312870
0.7763 Intermediate Similarity NPC199851
0.7763 Intermediate Similarity NPC294909
0.7763 Intermediate Similarity NPC254240
0.7763 Intermediate Similarity NPC128265
0.7763 Intermediate Similarity NPC604675
0.7632 Intermediate Similarity NPC100898
0.7632 Intermediate Similarity NPC148183
0.7632 Intermediate Similarity NPC21084
0.7632 Intermediate Similarity NPC152768
0.7632 Intermediate Similarity NPC605270
0.7436 Intermediate Similarity NPC293861
0.7273 Intermediate Similarity NPC107782
0.7273 Intermediate Similarity NPC486454
0.6795 Remote Similarity NPC486452
0.6795 Remote Similarity NPC74591
0.6341 Remote Similarity NPC131260
0.6296 Remote Similarity NPC313985
0.6296 Remote Similarity NPC249150
0.6296 Remote Similarity NPC486443
0.6296 Remote Similarity NPC486446
0.6296 Remote Similarity NPC33619
0.622 Remote Similarity NPC81654
0.622 Remote Similarity NPC175474
0.622 Remote Similarity NPC99921
0.6184 Remote Similarity NPC185200
0.6118 Remote Similarity NPC603895
0.6047 Remote Similarity NPC21638
0.5854 Remote Similarity NPC220151
0.5854 Remote Similarity NPC19692
0.5844 Remote Similarity NPC21174
0.5714 Remote Similarity NPC486444
0.5714 Remote Similarity NPC649
0.5625 Remote Similarity NPC474897
0.5581 Remote Similarity NPC611453
0.557 Remote Similarity NPC229173
0.5361 Remote Similarity NPC191489
0.5349 Remote Similarity NPC483467
0.5287 Remote Similarity NPC50503
0.5287 Remote Similarity NPC607669
0.5244 Remote Similarity NPC165441
0.5196 Remote Similarity NPC199607
0.5196 Remote Similarity NPC54591
0.5067 Remote Similarity NPC88097
0.5062 Remote Similarity NPC271797

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC486449 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
0.7763 Intermediate Similarity NPD4500 Approved
0.7763 Intermediate Similarity NPD4501 Approved
0.6296 Remote Similarity NPD4601 Phase 4
0.622 Remote Similarity NPD4600 Approved
0.5361 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