Natural Product: NPC249150

Natural Product IDNPC249150
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Methyl (1S,15S,18S,19R,20S)-18-Hydroxy-1,3,11,12,14,15,16,17,18,19,20,21-Dodecahydroyohimban-19-Carboxylate
IUPAC Name methyl (1S,15S,18S,19R,20S)-18-hydroxy-1,3,11,12,14,15,16,17,18,19,20,21-dodecahydroyohimban-19-carboxylate
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1526082
PubChem CID 120716
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000279] Alkaloids and derivatives
      • [CHEMONTID:0001786] Yohimbine 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 BLGXFZZNTVWLAY-FJDMERLMSA-N
Standard InCHI InChI=1S/C21H26N2O3/c1-26-21(25)19-15-10-17-20-14(13-4-2-3-5-16(13)22-20)8-9-23(17)11-12(15)6-7-18(19)24/h2-5,12,15,17-19,22,24H,6-11H2,1H3/t12-,15+,17+,18+,19-/m1/s1
SMILES COC(=O)[C@H]1[C@@H](O)CC[C@H]2[C@@H]1C[C@@H]1N(C2)CCc2c1[nH]c1c2cccc1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   354.19 Volume:   364.172
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Van der Waals volume.
Dense:   0.973 LogP:   2.567
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.579
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.721
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The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   26.0
TPSA:   65.56
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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:   0.773 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.875 Fsp3:   0.571
MCE-18:   95.333
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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:   0.296 Fluc inhibitor:   0.02
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.647
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.017
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.001 Promiscuous compounds:   0.845

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.495 MDCK Permeability:   -5.04
Pgp-inhibitor:   0.047 Pgp-substrate:   0.87
PAMPA:   0.173
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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%):   0.015 30% Bioavailability (F30%):   0.099
50% Bioavailability (F50%):   0.96

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.952 MRP1:   0.985
Plasma Protein Binding (PPB):   69.104% Volume Distribution (VD):   -0.007
Fu: 27.628%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.852
BSEP inhibitor:   0.961

ADMET: Metabolism

CYP1A2-inhibitor:   0.943 CYP1A2-substrate:   0.004
CYP2C19-inhibitor:   0.492 CYP2C19-substrate:   0.007
CYP2C9-inhibitor:   0.013 CYP2C9-substrate:   0.975
CYP2D6-inhibitor:   0.889 CYP2D6-substrate:   0.055
CYP3A4-inhibitor:   0.923 CYP3A4-substrate:   0.145
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.592
HLM stability:   0.292
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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):  9.036 Half-life (T1/2):  1.528

ADMET: Toxicity

hERG Blockers:  0.384 hERG Blockers (10um):  0.526
Human Hepatotoxicity (H-HT):  0.578 Drug-induced Liver Injury (DILI):  0.072
AMES Toxicity:  0.553 Rat Oral Acute Toxicity:  0.535
Maximum Recommended Daily Dose:  0.878 Skin Sensitization:  0.953
Carcinogencity:  0.692 Eye Corrosion:  0.0
Eye Irritation:  0.501 Respiratory Toxicity:  0.953
Drug-induced Neurotoxicity:  0.549 Ototoxicity:  0.533
Hematotoxicity:  0.092 Drug-induced Nephrotoxicity:  0.559
Genotoxicity:  0.219 RPMI-8226 Immunitoxicity:  0.046
A549 Cytotoxicity:  0.206 Hek293 Cytotoxicity:  0.36
BCF:   0.732
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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:   3.542
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.22
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.508
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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
NPO20258 Alstonia mairei Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20258 Alstonia mairei Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20258 Alstonia mairei Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO20258 Alstonia mairei Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO20258 Alstonia mairei 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
NPT583 Individual protein Inositol monophosphatase 1 Rattus norvegicus Potency = 31622.8 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT2 Others Unspecified n.a. Potency n.a. 10000.0 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 15848.9 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 35481.3 nM PubChem BioAssay data set

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 NPC249150 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 NPC313985
1.0 High Similarity NPC33619
0.9851 High Similarity NPC81654
0.7467 Intermediate Similarity NPC486452
0.7467 Intermediate Similarity NPC74591
0.6923 Remote Similarity NPC486443
0.6923 Remote Similarity NPC486446
0.642 Remote Similarity NPC50503
0.642 Remote Similarity NPC607669
0.6296 Remote Similarity NPC486449
0.6296 Remote Similarity NPC63199
0.6296 Remote Similarity NPC111602
0.6296 Remote Similarity NPC102338
0.6296 Remote Similarity NPC196251
0.6184 Remote Similarity NPC185200
0.6024 Remote Similarity NPC175474
0.6024 Remote Similarity NPC99921
0.5904 Remote Similarity NPC273374
0.5851 Remote Similarity NPC191489
0.5714 Remote Similarity NPC483467
0.5698 Remote Similarity NPC312870
0.5698 Remote Similarity NPC199851
0.5698 Remote Similarity NPC294909
0.5698 Remote Similarity NPC254240
0.5698 Remote Similarity NPC128265
0.5698 Remote Similarity NPC604675
0.5465 Remote Similarity NPC107782
0.5465 Remote Similarity NPC486454
0.5443 Remote Similarity NPC21174
0.5375 Remote Similarity NPC229173
0.5244 Remote Similarity NPC165441
0.5116 Remote Similarity NPC220151
0.5116 Remote Similarity NPC19692
0.5067 Remote Similarity NPC88097
0.506 Remote Similarity NPC474897
0.5056 Remote Similarity NPC611453

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC249150 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 NPD4601 Phase 4
0.9851 High Similarity NPD4600 Approved
0.5851 Remote Similarity NPD7708 Phase 4
0.5698 Remote Similarity NPD4500 Approved
0.5698 Remote Similarity NPD4501 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