Natural Product: NPC68842

Natural Product IDNPC68842
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 QLSITYRYHBQHBY-NWFPEMGYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000279] Alkaloids and derivatives
      • [CHEMONTID:0002748] Ibogan-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 QLSITYRYHBQHBY-NWFPEMGYSA-N
Standard InCHI InChI=1S/C20H26N2O2/c1-11(23)15-7-12-8-17-19-14(5-6-22(10-12)20(15)17)16-9-13(24-2)3-4-18(16)21-19/h3-4,9,11-12,15,17,20-21,23H,5-8,10H2,1-2H3/t11?,12-,15+,17+,20+/m1/s1
SMILES CC([C@@H]1C[C@@H]2C[C@H]3c4c(CCN(C2)[C@@H]13)c1cc(ccc1[nH]4)OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   326.2 Volume:   340.722
?
Van der Waals volume.
Dense:   0.957 LogP:   2.67
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.661
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.807
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   23.0
TPSA:   48.49
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   2.0 Rings:   6.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.892 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.142 Fsp3:   0.6
MCE-18:   92.625
?
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:   0.417 Fluc inhibitor:   0.121
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.921
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.227
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.001 Promiscuous compounds:   0.302

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.378 MDCK Permeability:   -5.036
Pgp-inhibitor:   0.005 Pgp-substrate:   0.829
PAMPA:   0.073
?
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):   0.003
20% Bioavailability (F20%):   0.168 30% Bioavailability (F30%):   0.396
50% Bioavailability (F50%):   0.896

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.098 MRP1:   0.923
Plasma Protein Binding (PPB):   75.706% Volume Distribution (VD):   0.321
Fu: 26.081%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.429
OATP1B3 inhibitor:   0.795 BCRP inhibitor:   0.546
BSEP inhibitor:   0.906

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.028
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.048
CYP2C9-inhibitor:   0.404 CYP2C9-substrate:   0.449
CYP2D6-inhibitor:   0.775 CYP2D6-substrate:   0.688
CYP3A4-inhibitor:   0.959 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.189
HLM stability:   0.501
?
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):  10.865 Half-life (T1/2):  1.539

ADMET: Toxicity

hERG Blockers:  0.49 hERG Blockers (10um):  0.577
Human Hepatotoxicity (H-HT):  0.635 Drug-induced Liver Injury (DILI):  0.601
AMES Toxicity:  0.797 Rat Oral Acute Toxicity:  0.83
Maximum Recommended Daily Dose:  0.974 Skin Sensitization:  0.71
Carcinogencity:  0.874 Eye Corrosion:  0.0
Eye Irritation:  0.131 Respiratory Toxicity:  0.979
Drug-induced Neurotoxicity:  0.866 Ototoxicity:  0.808
Hematotoxicity:  0.655 Drug-induced Nephrotoxicity:  0.947
Genotoxicity:  0.978 RPMI-8226 Immunitoxicity:  0.16
A549 Cytotoxicity:  0.848 Hek293 Cytotoxicity:  0.8
BCF:   1.509
?
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:   3.721
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.211
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.535
?
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
NPO31564 Cimicifuga foetida n.a. n.a. n.a. n.a. aerial part n.a. PMID[19280146]
NPO15890 Cimicifuga foetida Species Ranunculaceae Eukaryota Roots n.a. n.a. PMID[20121210]
NPO30530 Cimicifuga dahurica Species Ranunculaceae Eukaryota n.a. n.a. n.a. PMID[20192237]
NPO31564 Cimicifuga foetida n.a. n.a. n.a. rhizomes n.a. n.a. PMID[25136911]
NPO15373 Actaea dahurica Species Ranunculaceae Eukaryota Roots n.a. n.a. PMID[28558206]
NPO15373 Actaea dahurica Species Ranunculaceae Eukaryota n.a. n.a. n.a. PMID[32031796]
NPO22103 Ammi visnaga Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[38256954]
NPO30530 Cimicifuga dahurica Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO31564 Cimicifuga foetida n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO15373 Actaea dahurica Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22103 Ammi visnaga Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22103 Ammi visnaga Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO16242 Phlojodicarpus sibiricus Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO30530 Cimicifuga dahurica Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO31564 Cimicifuga foetida n.a. n.a. n.a. n.a. n.a. n.a. Database[HerDing]
NPO15373 Actaea dahurica Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15890 Cimicifuga foetida Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO22103 Ammi visnaga Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO16242 Phlojodicarpus sibiricus Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO22103 Ammi visnaga Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO16242 Phlojodicarpus sibiricus Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO31564 Cimicifuga foetida n.a. n.a. n.a. n.a. n.a. n.a. Database[TCM_Taiwan]
NPO30530 Cimicifuga dahurica Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO15373 Actaea dahurica Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO15890 Cimicifuga foetida Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO22103 Ammi visnaga Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15373 Actaea dahurica Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16242 Phlojodicarpus sibiricus Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15890 Cimicifuga foetida Species Ranunculaceae 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 NPC68842 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
0.8235 Intermediate Similarity NPC329793
0.8235 Intermediate Similarity NPC600762
0.7286 Intermediate Similarity NPC189812
0.7286 Intermediate Similarity NPC329688
0.64 Remote Similarity NPC329747
0.6375 Remote Similarity NPC474192
0.6282 Remote Similarity NPC471304
0.6184 Remote Similarity NPC478078
0.5814 Remote Similarity NPC478074
0.5733 Remote Similarity NPC21605
0.5733 Remote Similarity NPC215538
0.5686 Remote Similarity NPC485890
0.561 Remote Similarity NPC96321
0.561 Remote Similarity NPC111993
0.5421 Remote Similarity NPC485889
0.5301 Remote Similarity NPC475910
0.5222 Remote Similarity NPC485946

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC68842 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
0.8235 Intermediate Similarity NPD4118 Clinical (unspecified phase)

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