Natural Product: NPC591443

Natural Product IDNPC591443
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (2~{S})-2-[(2~{S},12~{b}~{S})-1,2,3,4,6,7,12,12~{b}-octahydroindolo[2,3-a]quinolizin-2-yl]but-3-en-1-ol
IUPAC Name (2~{S})-2-[(2~{S},12~{b}~{S})-1,2,3,4,6,7,12,12~{b}-octahydroindolo[2,3-a]quinolizin-2-yl]but-3-en-1-ol
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 RYMNVEAAYOFGCI-GLJUWKHASA-N
Standard InCHI InChI=1S/C19H24N2O/c1-2-13(12-22)14-7-9-21-10-8-16-15-5-3-4-6-17(15)20-19(16)18(21)11-14/h2-6,13-14,18,20,22H,1,7-12H2/t13-,14+,18+/m1/s1
SMILES C=C[C@H](CO)[C@H]1CCN2CCC3=C(NC4=CC=CC=C34)[C@@H]2C1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   296.19 Volume:   320.556
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Van der Waals volume.
Dense:   0.924 LogP:   2.653
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.604
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.16
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The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   21.0
TPSA:   39.26
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Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.853 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.781 Fsp3:   0.474
MCE-18:   70.0
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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:   0.284 Fluc inhibitor:   0.232
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.562
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.126
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.004 Promiscuous compounds:   0.28

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.253 MDCK Permeability:   -5.039
Pgp-inhibitor:   0.656 Pgp-substrate:   0.768
PAMPA:   0.002
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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%):   0.253 30% Bioavailability (F30%):   0.553
50% Bioavailability (F50%):   0.658

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.878 MRP1:   0.927
Plasma Protein Binding (PPB):   86.151% Volume Distribution (VD):   0.331
Fu: 16.845%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.811
OATP1B3 inhibitor:   0.454 BCRP inhibitor:   0.951
BSEP inhibitor:   0.945

ADMET: Metabolism

CYP1A2-inhibitor:   0.973 CYP1A2-substrate:   0.003
CYP2C19-inhibitor:   0.944 CYP2C19-substrate:   0.002
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.996
CYP2D6-inhibitor:   0.888 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.003
HLM stability:   0.001
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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):  11.007 Half-life (T1/2):  1.33

ADMET: Toxicity

hERG Blockers:  0.63 hERG Blockers (10um):  0.533
Human Hepatotoxicity (H-HT):  0.548 Drug-induced Liver Injury (DILI):  0.028
AMES Toxicity:  0.402 Rat Oral Acute Toxicity:  0.766
Maximum Recommended Daily Dose:  0.947 Skin Sensitization:  0.826
Carcinogencity:  0.618 Eye Corrosion:  0.0
Eye Irritation:  0.2 Respiratory Toxicity:  0.958
Drug-induced Neurotoxicity:  0.792 Ototoxicity:  0.376
Hematotoxicity:  0.052 Drug-induced Nephrotoxicity:  0.384
Genotoxicity:  0.946 RPMI-8226 Immunitoxicity:  0.032
A549 Cytotoxicity:  0.243 Hek293 Cytotoxicity:  0.47
BCF:   1.021
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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:   3.436
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.003
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.242
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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
NPO19678 Alstonia macrophylla Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[19191551]
NPO19678 Alstonia macrophylla Species Apocynaceae Eukaryota leaves Purwodadi Botanical Garden, Indonesia n.a. PMID[20189404]
NPO19678 Alstonia macrophylla Species Apocynaceae Eukaryota n.a. stem n.a. PMID[22148233]
NPO19678 Alstonia macrophylla Species Apocynaceae Eukaryota Barks n.a. n.a. PMID[23806072]
NPO32510 Rhazya stricta Species Apocynaceae Eukaryota Stems n.a. n.a. PMID[3373227]
NPO32510 Rhazya stricta Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[6619887]
NPO63491 Antirhea putaminosa Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19678 Alstonia macrophylla Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27273 Catharanthus longifolius Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO32510 Rhazya stricta Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27273 Catharanthus longifolius Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19678 Alstonia macrophylla Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19678 Alstonia macrophylla Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27273 Catharanthus longifolius Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO19678 Alstonia macrophylla Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO19678 Alstonia macrophylla 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 NPC591443 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
0.7121 Intermediate Similarity NPC317430
0.6667 Remote Similarity NPC185200
0.6667 Remote Similarity NPC229173
0.6533 Remote Similarity NPC486443
0.6533 Remote Similarity NPC486446
0.625 Remote Similarity NPC165441
0.6154 Remote Similarity NPC88097
0.5974 Remote Similarity NPC486452
0.5974 Remote Similarity NPC74591
0.5833 Remote Similarity NPC21174
0.5823 Remote Similarity NPC175474
0.5823 Remote Similarity NPC99921
0.5811 Remote Similarity NPC474897
0.5616 Remote Similarity NPC271797
0.5526 Remote Similarity NPC482948
0.55 Remote Similarity NPC313985
0.55 Remote Similarity NPC249150
0.55 Remote Similarity NPC273374
0.55 Remote Similarity NPC33619
0.55 Remote Similarity NPC483467
0.5432 Remote Similarity NPC81654
0.5244 Remote Similarity NPC50503
0.5244 Remote Similarity NPC607669
0.5181 Remote Similarity NPC611453
0.5065 Remote Similarity NPC472123
0.5065 Remote Similarity NPC611194
0.5065 Remote Similarity NPC611315
0.506 Remote Similarity NPC107782
0.506 Remote Similarity NPC486454

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC591443 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
0.55 Remote Similarity NPD4601 Phase 4
0.5432 Remote Similarity NPD4600 Approved

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