Natural Product: NPC145754

Natural Product IDNPC145754
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Chimonanthine
IUPAC Name (3aR,8bR)-8b-[(3aR,8bR)-3-methyl-1,2,3a,4-tetrahydropyrrolo[2,3-b]indol-8b-yl]-3-methyl-1,2,3a,4-tetrahydropyrrolo[2,3-b]indole
Synonyms Chimonanthine
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL464977
PubChem CID 442058
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000211] Indoles and derivatives
        • [CHEMONTID:0001733] Pyrroloindoles

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 HOYXPMHLHJOGHD-CZYKHXBRSA-N
Standard InCHI InChI=1S/C22H26N4/c1-25-13-11-21(15-7-3-5-9-17(15)23-19(21)25)22-12-14-26(2)20(22)24-18-10-6-4-8-16(18)22/h3-10,19-20,23-24H,11-14H2,1-2H3/t19-,20-,21+,22+/m1/s1
SMILES CN1CC[C@@]2(c3ccccc3N[C@H]12)[C@@]12CCN(C)[C@H]2Nc2ccccc12

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   346.22 Volume:   365.898
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Van der Waals volume.
Dense:   0.946 LogP:   2.179
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.245
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.022
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The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   28.0
TPSA:   30.54
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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:   0.831 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.22 Fsp3:   0.455
MCE-18:   112.0
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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:   0.184 Fluc inhibitor:   0.001
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.933
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.358
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.003 Promiscuous compounds:   0.621

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.999 MDCK Permeability:   -4.748
Pgp-inhibitor:   0.0 Pgp-substrate:   0.996
PAMPA:   0.005
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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%):   0.871 30% Bioavailability (F30%):   1.0
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   1.0 MRP1:   0.989
Plasma Protein Binding (PPB):   55.798% Volume Distribution (VD):   0.673
Fu: 39.103%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.006
OATP1B3 inhibitor:   0.0 BCRP inhibitor:   0.074
BSEP inhibitor:   0.001

ADMET: Metabolism

CYP1A2-inhibitor:   0.996 CYP1A2-substrate:   0.008
CYP2C19-inhibitor:   0.996 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.307 CYP2C9-substrate:   0.535
CYP2D6-inhibitor:   0.992 CYP2D6-substrate:   0.004
CYP3A4-inhibitor:   0.998 CYP3A4-substrate:   0.365
CYP2B6-substrate:   0.067 CYP2C8-inhibitor:   0.0
HLM stability:   0.031
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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):  16.193 Half-life (T1/2):  5.759

ADMET: Toxicity

hERG Blockers:  0.211 hERG Blockers (10um):  0.418
Human Hepatotoxicity (H-HT):  0.525 Drug-induced Liver Injury (DILI):  0.109
AMES Toxicity:  0.487 Rat Oral Acute Toxicity:  0.824
Maximum Recommended Daily Dose:  0.866 Skin Sensitization:  0.777
Carcinogencity:  0.155 Eye Corrosion:  0.0
Eye Irritation:  0.148 Respiratory Toxicity:  0.962
Drug-induced Neurotoxicity:  0.907 Ototoxicity:  0.436
Hematotoxicity:  0.457 Drug-induced Nephrotoxicity:  0.72
Genotoxicity:  0.957 RPMI-8226 Immunitoxicity:  0.092
A549 Cytotoxicity:  0.1 Hek293 Cytotoxicity:  0.211
BCF:   1.553
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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:   3.849
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.776
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.482
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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
NPO13462 Plocamium costatum Species Plocamiaceae Eukaryota n.a. n.a. n.a. PMID[10075796]
NPO40170 Idiospermum australiense Species Calycanthaceae Eukaryota Seeds n.a. n.a. PMID[7595588]
NPO13462 Plocamium costatum Species Plocamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7839 Rosa sericea Species Rosaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7839 Rosa sericea Species Rosaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7839 Rosa sericea Species Rosaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO16162 Cyclamen cyprium Species Primulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15298 Epilachna borealis Species Coccinellidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14328 Aconitum ouvrardianum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12017 Juniperus mexicana Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7839 Rosa sericea Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13462 Plocamium costatum Species Plocamiaceae 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
NPT2 Others Unspecified n.a. Activity = 58.3 % PMID[7595588]

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 NPC145754 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 NPC252794
0.64 Remote Similarity NPC606643

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC145754 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