Natural Product: NPC494531

Natural Product IDNPC494531
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (1~{R},9~{R},10~{S},12~{S},13~{S},14~{R},16~{S},17~{S},18~{R})-13-ethyl-8-methyl-8,15-diazahexacyclo[14.2.1.0^{1,9}.0^{2,7}.0^{10,15}.0^{12,17}]nonadeca-2,4,6-triene-14,18-diol
IUPAC Name (1~{R},9~{R},10~{S},12~{S},13~{S},14~{R},16~{S},17~{S},18~{R})-13-ethyl-8-methyl-8,15-diazahexacyclo[14.2.1.0^{1,9}.0^{2,7}.0^{10,15}.0^{12,17}]nonadeca-2,4,6-triene-14,18-diol
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 CJDRUOGAGYHKKD-BDXZSHBPSA-N
Standard InCHI InChI=1S/C20H26N2O2/c1-3-10-11-8-14-17-20(12-6-4-5-7-13(12)21(17)2)9-15(16(11)18(20)23)22(14)19(10)24/h4-7,10-11,14-19,23-24H,3,8-9H2,1-2H3/t10-,11+,14-,15-,16-,17-,18+,19+,20+/m0/s1
SMILES CC[C@H]1[C@H]2C[C@H]3[C@@H]4N(C)C5=CC=CC=C5[C@]45C[C@@H]([C@H]2[C@H]5O)N3[C@@H]1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   326.2 Volume:   334.802
?
Van der Waals volume.
Dense:   0.974 LogP:   2.385
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.682
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.78
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   24.0
TPSA:   46.94
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   2.0 Rings:   7.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.822 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   6.381 Fsp3:   0.7
MCE-18:   153.353
?
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:   0.35 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.385
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.0
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.005 Promiscuous compounds:   0.054

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.918 MDCK Permeability:   -4.918
Pgp-inhibitor:   0.003 Pgp-substrate:   0.999
PAMPA:   0.091
?
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):   0.004
20% Bioavailability (F20%):   0.935 30% Bioavailability (F30%):   0.998
50% Bioavailability (F50%):   0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.94 MRP1:   0.851
Plasma Protein Binding (PPB):   84.179% Volume Distribution (VD):   0.617
Fu: 17.884%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.199
OATP1B3 inhibitor:   0.042 BCRP inhibitor:   0.053
BSEP inhibitor:   0.176

ADMET: Metabolism

CYP1A2-inhibitor:   0.905 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.002 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.284
CYP2D6-inhibitor:   0.033 CYP2D6-substrate:   0.158
CYP3A4-inhibitor:   0.769 CYP3A4-substrate:   0.629
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.024
HLM stability:   0.45
?
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):  10.451 Half-life (T1/2):  2.162

ADMET: Toxicity

hERG Blockers:  0.211 hERG Blockers (10um):  0.614
Human Hepatotoxicity (H-HT):  0.669 Drug-induced Liver Injury (DILI):  0.384
AMES Toxicity:  0.542 Rat Oral Acute Toxicity:  0.335
Maximum Recommended Daily Dose:  0.359 Skin Sensitization:  0.947
Carcinogencity:  0.291 Eye Corrosion:  0.004
Eye Irritation:  0.474 Respiratory Toxicity:  0.757
Drug-induced Neurotoxicity:  0.183 Ototoxicity:  0.656
Hematotoxicity:  0.734 Drug-induced Nephrotoxicity:  0.493
Genotoxicity:  0.14 RPMI-8226 Immunitoxicity:  0.068
A549 Cytotoxicity:  0.241 Hek293 Cytotoxicity:  0.329
BCF:   0.832
?
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:   3.26
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.5
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.956
?
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
NPO947 Rauvolfia vomitoria Species Apocynaceae Eukaryota n.a. n.a. n.a. DOI[10.1080/01496395.2011.635623]
NPO947 Rauvolfia vomitoria Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[38416335]
NPO50940 Rauvolfia sevenetii Genus Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO42126 Rauvolfia biauriculata Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO60854 Rauvolfia confertiflora Genus Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO52062 Melodinus balansae var.paucivenosus Genus Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO62870 Rauwolfia caffra n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO49099 Rauvolfia volkensii Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO49124 Rauvolfia sellowii Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO62628 Rauvolfia spathulata Genus Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO42570 Rauvolfia verticillata var.hainanensis Genus Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO42101 Rauvolfia suaveolens Genus Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO60891 Rauvolfia macrophylla Genus Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO63699 Rauwolfia serpentina Benth ex Kurz. n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO10333 Rauvolfia caffra Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO60093 Rauvolfia mombasiana Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6275 Rauvolfia cumminsii Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO42948 Rauvolfia cubana Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO49604 Rauwolfia canescens n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO43922 Rauvolfia densiflora Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO52409 Tonduzia longiflora Genus Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO44432 Rauvolfia viridis Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO62254 Rauvolfia verticillata var.rubrocarpa Genus Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO60644 Rauvolfia oreogiton Genus Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO58065 Rauvolfia littoralis Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO63425 Rauvolfia ligustrina Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO57990 Rauvolfia indecora Genus Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO46036 Rauvolfia heterophylla Genus Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO54435 Rauvolfia fruticosa Genus Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5135 Rauvolfia perakensis Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO60184 Rauvolfia degeneri Genus Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO56053 Rauvolfia chinensis Genus Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO61691 Rauvolfia cambodiana Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO56719 Rauvolfia boliviana Genus Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO61611 Rauvolfia balansaevar.basicola Genus Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO42569 Rauvolfia balansae ssp.schumanniana Genus Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO51114 Rauvolfia balansae ssp.balansae Genus Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO46406 Aspidosperma spegazzinii Genus Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO53072 Rauvolfia canescens Genus Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29265 Melodinus balansae Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16358 Rauvolfia obscura Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO53085 Rauwolfia serpentina Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23579 Rauvolfia yunnanensis Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7282 Rauvolfia serpentina Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22083 Rauvolfia nitida Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10353 Rauvolfia tetraphylla Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18714 Rauvolfia verticillata Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO947 Rauvolfia vomitoria Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22083 Rauvolfia nitida Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18714 Rauvolfia verticillata Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO23579 Rauvolfia yunnanensis Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5135 Rauvolfia perakensis Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO947 Rauvolfia vomitoria Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO16358 Rauvolfia obscura Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO6275 Rauvolfia cumminsii Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO29265 Melodinus balansae Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO10333 Rauvolfia caffra Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO23579 Rauvolfia yunnanensis Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO947 Rauvolfia vomitoria Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO16358 Rauvolfia obscura Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO22083 Rauvolfia nitida Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7282 Rauvolfia serpentina Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5135 Rauvolfia perakensis Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18714 Rauvolfia verticillata Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO6275 Rauvolfia cumminsii Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10333 Rauvolfia caffra Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29265 Melodinus balansae Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5135 Rauvolfia perakensis Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO22083 Rauvolfia nitida Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO7282 Rauvolfia serpentina Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO7282 Rauvolfia serpentina Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29265 Melodinus balansae Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10353 Rauvolfia tetraphylla Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO947 Rauvolfia vomitoria 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 NPC494531 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 NPC610950
1.0 High Similarity NPC612032

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC494531 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
1.0 High Similarity NPD4120 Approved
1.0 High Similarity NPD4121 Phase 3

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