Natural Product: NPC44773

Natural Product IDNPC44773
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Olivacine
IUPAC Name 1,5-dimethyl-6H-pyrido[4,3-b]carbazole
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL306472
PubChem CID 5281407
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000211] Indoles and derivatives
        • [CHEMONTID:0000210] Carbazoles

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 ZIXGXMMUKPLXBB-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H14N2/c1-10-12-7-8-18-11(2)14(12)9-15-13-5-3-4-6-16(13)19-17(10)15/h3-9,19H,1-2H3
SMILES Cc1nccc2c1cc1c3ccccc3[nH]c1c2C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   246.12 Volume:   269.264
?
Van der Waals volume.
Dense:   0.914 LogP:   4.557
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.633
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.678
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The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   20.0
TPSA:   28.68
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.486 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.255 Fsp3:   0.118
MCE-18:   20.0
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.656 Fluc inhibitor:   0.939
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.943
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.485
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.03 Promiscuous compounds:   0.729

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.77 MDCK Permeability:   -4.642
Pgp-inhibitor:   0.067 Pgp-substrate:   0.356
PAMPA:   0.139
?
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%):   0.006 30% Bioavailability (F30%):   0.019
50% Bioavailability (F50%):   0.277

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.918 MRP1:   0.986
Plasma Protein Binding (PPB):   97.263% Volume Distribution (VD):   -0.031
Fu: 2.415%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.982
OATP1B3 inhibitor:   0.986 BCRP inhibitor:   0.065
BSEP inhibitor:   0.997

ADMET: Metabolism

CYP1A2-inhibitor:   0.986 CYP1A2-substrate:   0.603
CYP2C19-inhibitor:   0.446 CYP2C19-substrate:   0.388
CYP2C9-inhibitor:   0.947 CYP2C9-substrate:   0.982
CYP2D6-inhibitor:   0.988 CYP2D6-substrate:   0.815
CYP3A4-inhibitor:   0.955 CYP3A4-substrate:   0.764
CYP2B6-substrate:   0.013 CYP2C8-inhibitor:   1.0
HLM stability:   0.629
?
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):  8.261 Half-life (T1/2):  0.638

ADMET: Toxicity

hERG Blockers:  0.352 hERG Blockers (10um):  0.568
Human Hepatotoxicity (H-HT):  0.762 Drug-induced Liver Injury (DILI):  0.903
AMES Toxicity:  0.808 Rat Oral Acute Toxicity:  0.804
Maximum Recommended Daily Dose:  0.806 Skin Sensitization:  0.707
Carcinogencity:  0.865 Eye Corrosion:  0.001
Eye Irritation:  0.935 Respiratory Toxicity:  0.946
Drug-induced Neurotoxicity:  0.905 Ototoxicity:  0.607
Hematotoxicity:  0.571 Drug-induced Nephrotoxicity:  0.808
Genotoxicity:  0.536 RPMI-8226 Immunitoxicity:  0.14
A549 Cytotoxicity:  0.279 Hek293 Cytotoxicity:  0.437
BCF:   1.845
?
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:   4.073
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.795
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.746
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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
NPO12133 Corchorus olitorius Species Malvaceae Eukaryota n.a. n.a. n.a. PMID[38543013]
NPO12133 Corchorus olitorius Species Malvaceae Eukaryota n.a. leaf n.a. PMID[9658577]
NPO12133 Corchorus olitorius Species Malvaceae Eukaryota n.a. leaf n.a. Database[Article]
NPO5413 Adonis mongolica Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22383 Aspidosperma nigricans Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14143 Aspidosperma campus-belus Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18827 Aspidosperma olivaceum Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12133 Corchorus olitorius Species Malvaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12133 Corchorus olitorius Species Malvaceae Eukaryota n.a. n.a. Database[FooDB]
NPO12133 Corchorus olitorius Species Malvaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO12133 Corchorus olitorius Species Malvaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO22383 Aspidosperma nigricans Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18827 Aspidosperma olivaceum Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14143 Aspidosperma campus-belus Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5413 Adonis mongolica Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12985 Corchorus capsularis Species Malvaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12133 Corchorus olitorius Species Malvaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12133 Corchorus olitorius Species Malvaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18827 Aspidosperma olivaceum Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14143 Aspidosperma campus-belus Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO22383 Aspidosperma nigricans Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5413 Adonis mongolica Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12985 Corchorus capsularis Species Malvaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18827 Aspidosperma olivaceum Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12985 Corchorus capsularis Species Malvaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5413 Adonis mongolica 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
NPT1396 Cell line NCI-H69 Homo sapiens IC50 = 1700.0 nM PMID[1479585]
NPT2943 Cell line NCI-H417 Homo sapiens IC50 = 3400.0 nM PMID[1479585]
NPT397 Cell line NCI-H460 Homo sapiens IC50 = 1600.0 nM PMID[1479585]
NPT2466 Cell line NCI-H358 Homo sapiens IC50 = 2300.0 nM PMID[1479585]
NPT137 Cell line L1210 Mus musculus ILS = 35.0 % PMID[4009591]
NPT137 Cell line L1210 Mus musculus ID50 = 2.03 uM PMID[4009591]
NPT474 Organism Plasmodium berghei Plasmodium berghei Inhibition = 90.0 % PMID[24813729]
NPT474 Organism Plasmodium berghei Plasmodium berghei Inhibition = 48.0 % PMID[24813729]
NPT757 Organism Plasmodium falciparum 3D7 Plasmodium falciparum 3D7 IC50 = 1200.0 nM PMID[24813729]
NPT2 Others Unspecified n.a. Ratio = 1.0 n.a. PMID[8035425]
NPT485 Organism Plasmodium falciparum (isolate K1 / Thailand) Plasmodium falciparum K1 IC50 = 400.0 nM PMID[24813729]
NPT2 Others Unspecified n.a. Ratio IC50 > 290.0 n.a. PMID[24813729]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT605 Organism Homo sapiens Homo sapiens TGI = 3600.0 nM PMID[8035425]
NPT605 Organism Homo sapiens Homo sapiens TGI = 3700.0 nM PMID[8035425]
NPT605 Organism Homo sapiens Homo sapiens TGI correlation coefficient < 0.5 n.a. PMID[8035425]





 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 NPC44773 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
0.5439 Remote Similarity NPC215584
0.5385 Remote Similarity NPC179787

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC44773 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