Natural Product: NPC5630

Natural Product IDNPC5630
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Melodinine P
IUPAC Name n.a.
Synonyms Melodinine P
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2011507
PubChem CID 57333046
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000279] Alkaloids and derivatives
      • [CHEMONTID:0002672] Plumeran-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 BCQPXUWNKBYVDE-ACRUOGEOSA-N
Standard InCHI InChI=1S/C21H24N2O3/c1-3-20-7-4-9-23-10-8-21(19(20)23)15-11-13(24)5-6-16(15)22-17(21)14(12-20)18(25)26-2/h4-7,11,19,22,24H,3,8-10,12H2,1-2H3/t19-,20-,21-/m0/s1
SMILES COC(=O)C1=C2Nc3c([C@@]42[C@@H]2[C@@](C1)(CC)C=CCN2CC4)cc(cc3)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   352.18 Volume:   361.535
?
Van der Waals volume.
Dense:   0.974 LogP:   2.562
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.655
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.897
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   24.0
TPSA:   61.8
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   5.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.487 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.696 Fsp3:   0.476
MCE-18:   129.097
?
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:   0.198 Fluc inhibitor:   0.001
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.572
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.308
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.002 Promiscuous compounds:   0.046

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.058 MDCK Permeability:   -4.782
Pgp-inhibitor:   0.0 Pgp-substrate:   1.0
PAMPA:   0.033
?
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%):   0.997 30% Bioavailability (F30%):   1.0
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.99 MRP1:   0.995
Plasma Protein Binding (PPB):   92.298% Volume Distribution (VD):   0.604
Fu: 6.923%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.038
OATP1B3 inhibitor:   0.004 BCRP inhibitor:   0.002
BSEP inhibitor:   0.188

ADMET: Metabolism

CYP1A2-inhibitor:   0.928 CYP1A2-substrate:   0.014
CYP2C19-inhibitor:   0.355 CYP2C19-substrate:   0.056
CYP2C9-inhibitor:   0.077 CYP2C9-substrate:   0.18
CYP2D6-inhibitor:   0.621 CYP2D6-substrate:   0.63
CYP3A4-inhibitor:   0.97 CYP3A4-substrate:   0.761
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.462
HLM stability:   0.777
?
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):  12.278 Half-life (T1/2):  1.316

ADMET: Toxicity

hERG Blockers:  0.165 hERG Blockers (10um):  0.401
Human Hepatotoxicity (H-HT):  0.661 Drug-induced Liver Injury (DILI):  0.267
AMES Toxicity:  0.339 Rat Oral Acute Toxicity:  0.647
Maximum Recommended Daily Dose:  0.861 Skin Sensitization:  0.935
Carcinogencity:  0.406 Eye Corrosion:  0.004
Eye Irritation:  0.47 Respiratory Toxicity:  0.94
Drug-induced Neurotoxicity:  0.763 Ototoxicity:  0.412
Hematotoxicity:  0.531 Drug-induced Nephrotoxicity:  0.747
Genotoxicity:  0.992 RPMI-8226 Immunitoxicity:  0.05
A549 Cytotoxicity:  0.238 Hek293 Cytotoxicity:  0.605
BCF:   1.156
?
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:   3.92
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.033
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.657
?
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
NPO33137 melodinus suaveolens Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[22260257]
NPO33137 melodinus suaveolens Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[24274642]

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
NPT116 Cell line HL-60 Homo sapiens IC50 = 28100.0 nM PMID[22934671]
NPT659 Cell line SMMC-7721 Homo sapiens IC50 > 40000.0 nM PMID[14695794]
NPT81 Cell line A549 Homo sapiens IC50 > 40000.0 nM PMID[22365754]
NPT83 Cell line MCF7 Homo sapiens IC50 > 40000.0 nM PMID[9514009]
NPT660 Cell line SW480 Homo sapiens IC50 > 40000.0 nM PMID[20621475]
NPT82 Cell line MDA-MB-231 Homo sapiens Activity n.a. n.a. n.a. PMID[37122543]
NPT82 Cell line MDA-MB-231 Homo sapiens IC50 = 1060.0 nM PMID[37122543]

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 NPC5630 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
0.8 Intermediate Similarity NPC203628
0.7792 Intermediate Similarity NPC119722
0.76 Intermediate Similarity NPC123241
0.7436 Intermediate Similarity NPC303214
0.725 Intermediate Similarity NPC232600
0.7051 Intermediate Similarity NPC475147
0.6962 Remote Similarity NPC22476
0.679 Remote Similarity NPC475133
0.6452 Remote Similarity NPC77812
0.6452 Remote Similarity NPC303387
0.6 Remote Similarity NPC483959
0.593 Remote Similarity NPC186669
0.5747 Remote Similarity NPC87714
0.5747 Remote Similarity NPC269449
0.5647 Remote Similarity NPC128948
0.5577 Remote Similarity NPC469722
0.5495 Remote Similarity NPC19175
0.5463 Remote Similarity NPC485928
0.5463 Remote Similarity NPC477068
0.5455 Remote Similarity NPC293458
0.5333 Remote Similarity NPC485981
0.5315 Remote Similarity NPC256381
0.5294 Remote Similarity NPC61013
0.5056 Remote Similarity NPC159963
0.5053 Remote Similarity NPC128476

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC5630 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
NPD

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