Natural Product: NPC11391

Natural Product IDNPC11391
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 QVNXPWJNUKKMHP-SJSDVCPDSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 443358
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000279] Alkaloids and derivatives
      • [CHEMONTID:0002755] Aspidospermatan-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 QVNXPWJNUKKMHP-SJSDVCPDSA-N
Standard InCHI InChI=1S/C21H24N2O4/c1-11(24)21-9-12(18(25)26-2)16-20(13-5-3-4-6-14(13)22-16)7-8-23(19(20)21)10-15-17(21)27-15/h3-6,11,15,17,19,22,24H,7-10H2,1-2H3/t11?,15?,17?,19-,20+,21+/m1/s1
SMILES CC([C@@]12CC(=C3[C@]4(CCN(CC5C1O5)[C@@H]24)c1ccccc1N3)C(=O)OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   368.17 Volume:   364.406
?
Van der Waals volume.
Dense:   1.01 LogP:   1.698
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.089
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.066
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   26.0
TPSA:   74.33
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   2.0 Rings:   6.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.607 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.195 Fsp3:   0.571
MCE-18:   154.545
?
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:   0.056 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.508
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.163
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.002 Promiscuous compounds:   0.003

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.471 MDCK Permeability:   -4.883
Pgp-inhibitor:   0.016 Pgp-substrate:   1.0
PAMPA:   0.099
?
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%):   0.55 30% Bioavailability (F30%):   0.971
50% Bioavailability (F50%):   0.99

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.811 MRP1:   0.993
Plasma Protein Binding (PPB):   76.86% Volume Distribution (VD):   0.428
Fu: 23.087%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.432
OATP1B3 inhibitor:   0.045 BCRP inhibitor:   0.238
BSEP inhibitor:   0.421

ADMET: Metabolism

CYP1A2-inhibitor:   0.862 CYP1A2-substrate:   0.088
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.041
CYP2C9-inhibitor:   0.381 CYP2C9-substrate:   0.389
CYP2D6-inhibitor:   0.421 CYP2D6-substrate:   0.38
CYP3A4-inhibitor:   0.998 CYP3A4-substrate:   0.733
CYP2B6-substrate:   0.026 CYP2C8-inhibitor:   0.0
HLM stability:   0.282
?
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):  10.601 Half-life (T1/2):  1.559

ADMET: Toxicity

hERG Blockers:  0.109 hERG Blockers (10um):  0.274
Human Hepatotoxicity (H-HT):  0.769 Drug-induced Liver Injury (DILI):  0.533
AMES Toxicity:  0.573 Rat Oral Acute Toxicity:  0.662
Maximum Recommended Daily Dose:  0.745 Skin Sensitization:  0.859
Carcinogencity:  0.589 Eye Corrosion:  0.0
Eye Irritation:  0.064 Respiratory Toxicity:  0.895
Drug-induced Neurotoxicity:  0.382 Ototoxicity:  0.632
Hematotoxicity:  0.54 Drug-induced Nephrotoxicity:  0.843
Genotoxicity:  0.999 RPMI-8226 Immunitoxicity:  0.035
A549 Cytotoxicity:  0.092 Hek293 Cytotoxicity:  0.275
BCF:   0.646
?
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:   3.41
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.107
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.258
?
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
NPO5881 Catharanthus roseus Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[ 3619437]
NPO5881 Catharanthus roseus Species Apocynaceae Eukaryota n.a. n.a. n.a. DOI[10.1002/btpr.97]
NPO5881 Catharanthus roseus Species Apocynaceae Eukaryota n.a. n.a. n.a. DOI[10.1007/s11738-010-0631-6]
NPO5881 Catharanthus roseus Species Apocynaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/j.plaphy.2018.10.015]
NPO5881 Catharanthus roseus Species Apocynaceae Eukaryota n.a. n.a. n.a. DOI[10.1080/17429145.2017.1293852]
NPO5881 Catharanthus roseus Species Apocynaceae Eukaryota n.a. n.a. n.a. DOI[10.1186/1750-2187-3-9]
NPO5881 Catharanthus roseus Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[12628396]
NPO5881 Catharanthus roseus Species Apocynaceae Eukaryota Hairy roots n.a. n.a. PMID[19271765]
NPO5881 Catharanthus roseus Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[26285573]
NPO5881 Catharanthus roseus Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[6619887]
NPO5881 Catharanthus roseus Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[6631435]
NPO5881 Catharanthus roseus Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[7264679]
NPO5881 Catharanthus roseus Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[7264682]
NPO5881 Catharanthus roseus Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[7320741]
NPO16987 Vinca erecta Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5881 Catharanthus roseus Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5881 Catharanthus roseus Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO16987 Vinca erecta Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO16987 Vinca erecta Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5881 Catharanthus roseus Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5881 Catharanthus roseus Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO5881 Catharanthus roseus Species Apocynaceae 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 NPC11391 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 NPC159963
0.6375 Remote Similarity NPC61013
0.622 Remote Similarity NPC123241
0.6092 Remote Similarity NPC97584
0.6047 Remote Similarity NPC186669
0.6047 Remote Similarity NPC14994
0.5977 Remote Similarity NPC485981
0.593 Remote Similarity NPC195636
0.5778 Remote Similarity NPC19175
0.573 Remote Similarity NPC476069
0.5568 Remote Similarity NPC293458
0.5545 Remote Similarity NPC485975
0.5495 Remote Similarity NPC18809
0.5495 Remote Similarity NPC199826
0.5439 Remote Similarity NPC208310
0.5439 Remote Similarity NPC301174
0.5349 Remote Similarity NPC99043
0.5349 Remote Similarity NPC218594
0.5333 Remote Similarity NPC87714
0.5273 Remote Similarity NPC608626
0.5238 Remote Similarity NPC25401
0.5093 Remote Similarity NPC469722
0.5059 Remote Similarity NPC248117
0.5059 Remote Similarity NPC238013
0.5057 Remote Similarity NPC203202
0.5057 Remote Similarity NPC264482
0.5056 Remote Similarity NPC128948
0.5054 Remote Similarity NPC189661

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC11391 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