Natural Product: NPC124099

Natural Product IDNPC124099
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 JOPOVCBBYLSVDA-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 29131
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000422] Homogeneous metal compounds
      • [CHEMONTID:0000426] Homogeneous transition metal 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 JOPOVCBBYLSVDA-UHFFFAOYSA-N
Standard InCHI InChI=1S/Cr/q+6
SMILES [Cr+6]

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   51.94 Volume:   0.0
?
Van der Waals volume.
Dense:   inf LogP:   1.447
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.535
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.336
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   0.0
TPSA:   0.0
?
Topological Polar Surface Area.
 H-Bond Acceptor:   0.0
H-Bond Donor:   0.0 Rings:   0.0
Heavy Atoms:   1.0

MedChem Properties

QED Drug-Likeness Score:   0.364 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   8.48 Fsp3:   0.0
MCE-18:   0.0
?
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:   Accepted BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.021 Fluc inhibitor:   0.003
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.564
?
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:   0.838 Promiscuous compounds:   0.65

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.224 MDCK Permeability:   -4.446
Pgp-inhibitor:   0.377 Pgp-substrate:   0.175
PAMPA:   0.336
?
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):   0.244
20% Bioavailability (F20%):   0.28 30% Bioavailability (F30%):   0.484
50% Bioavailability (F50%):   0.582

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.323 MRP1:   0.592
Plasma Protein Binding (PPB):   19.444% Volume Distribution (VD):   -0.088
Fu: 74.775%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.891
OATP1B3 inhibitor:   0.948 BCRP inhibitor:   0.277
BSEP inhibitor:   0.651

ADMET: Metabolism

CYP1A2-inhibitor:   0.329 CYP1A2-substrate:   0.92
CYP2C19-inhibitor:   0.161 CYP2C19-substrate:   0.612
CYP2C9-inhibitor:   0.18 CYP2C9-substrate:   0.096
CYP2D6-inhibitor:   0.062 CYP2D6-substrate:   0.015
CYP3A4-inhibitor:   0.246 CYP3A4-substrate:   0.304
CYP2B6-substrate:   0.087 CYP2C8-inhibitor:   0.357
HLM stability:   0.436
?
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):  7.615 Half-life (T1/2):  2.7

ADMET: Toxicity

hERG Blockers:  0.204 hERG Blockers (10um):  0.981
Human Hepatotoxicity (H-HT):  1.0 Drug-induced Liver Injury (DILI):  1.0
AMES Toxicity:  0.981 Rat Oral Acute Toxicity:  0.698
Maximum Recommended Daily Dose:  0.999 Skin Sensitization:  1.0
Carcinogencity:  1.0 Eye Corrosion:  0.0
Eye Irritation:  0.998 Respiratory Toxicity:  1.0
Drug-induced Neurotoxicity:  1.0 Ototoxicity:  1.0
Hematotoxicity:  1.0 Drug-induced Nephrotoxicity:  1.0
Genotoxicity:  1.0 RPMI-8226 Immunitoxicity:  0.002
A549 Cytotoxicity:  0.0 Hek293 Cytotoxicity:  1.0
BCF:   0.862
?
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:   3.414
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.34
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.938
?
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
NPO27302 Cinnamomum insularimontanum Species Lauraceae Eukaryota n.a. root n.a. PMID[16168547]
NPO9518 Gardenia jasminoides Species Rubiaceae Eukaryota Fruits n.a. n.a. PMID[16309325]
NPO9518 Gardenia jasminoides Species Rubiaceae Eukaryota n.a. Seoul, Korea 2000-Jun PMID[16643034]
NPO9518 Gardenia jasminoides Species Rubiaceae Eukaryota fruit n.a. n.a. PMID[18505286]
NPO9518 Gardenia jasminoides Species Rubiaceae Eukaryota fruit n.a. n.a. PMID[19650637]
NPO9518 Gardenia jasminoides Species Rubiaceae Eukaryota fruits n.a. n.a. PMID[23305920]
NPO9518 Gardenia jasminoides Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[32141747]
NPO9518 Gardenia jasminoides Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21563 Ootheca mantidis n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO18039 Herba dendrobii n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO9518 Gardenia jasminoides Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21563 Ootheca mantidis n.a. n.a. n.a. n.a. n.a. n.a. Database[HerDing]
NPO18039 Herba dendrobii n.a. n.a. n.a. n.a. n.a. n.a. Database[TCMID]
NPO9518 Gardenia jasminoides Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27302 Cinnamomum insularimontanum Species Lauraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21563 Ootheca mantidis n.a. n.a. n.a. n.a. n.a. n.a. Database[TCMID]
NPO9518 Gardenia jasminoides Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO9518 Gardenia jasminoides Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO9518 Gardenia jasminoides Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27302 Cinnamomum insularimontanum Species Lauraceae 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
- Rattus norvegicus BMCL (10 HEC) = 0.034 mg/m3 ToxVal
- Rattus norvegicus NOAEL = 25.0 mg/L ToxVal
- Rattus norvegicus NOAEL (ADJ) = 2.5 mg/kg-day ToxVal
- Rattus norvegicus NOAEL = 2.4 mg/kg-day ToxVal
- Rattus norvegicus BMDL (05) = 0.2 mg/kg-day ToxVal
- Rattus norvegicus LOAEL = 13.14 mg/kg-day ToxVal
- Rattus norvegicus NOAEL = 3.28 mg/kg-day ToxVal
- Rattus norvegicus BMCL = 0.016 mg/m3 ToxVal
- Rattus norvegicus BMCL (HEC) = 0.01 mg/m3 ToxVal
- Rattus norvegicus BMDL (2 SD) = 0.52 mg chromium(VI)/kg-day ToxVal
- Mus musculus BMDL (10) = 0.11 mg/kg-day ToxVal
- Mus musculus BMDL (10) = 1.0 mg/kg-day ToxVal
- Mus musculus BMDL (10) = 0.09 mg chromium(VI)/kg-day ToxVal
- Homo sapiens RfC = 0.0003 mg/m3 ToxVal
- Homo sapiens RfD = 0.005 mg/kg-day ToxVal
- Homo sapiens RfC = 0.0001 mg/m3 ToxVal
- Homo sapiens RfD = 0.003 mg/kg-day ToxVal
- Homo sapiens cancer unit risk = 84.0 (mg/m3)-1 ToxVal
- Homo sapiens cancer slope factor = 0.5 (mg/kg-day)-1 ToxVal
- Homo sapiens cancer unit risk = 12.0 (mg/m3)-1 ToxVal
- Homo sapiens RfC = 8e-06 mg/m3 ToxVal
- Homo sapiens LOAEL (ADJ) = 0.000714 mg/m3 ToxVal
- Homo sapiens LOAEL = 0.002 mg/m3 ToxVal
- Homo sapiens RfD = 0.02 mg/kg-day ToxVal
- Homo sapiens cancer unit risk = 76.0 (mg/m3)-1 ToxVal
- Homo sapiens cancer slope factor = 320.0 (mg/kg-day)-1 ToxVal
- Homo sapiens MEG = 0.126 mg/L ToxVal
- Homo sapiens MEG = 1910.0 mg/kg ToxVal
- Homo sapiens MEG = 0.0004 mg/m3 ToxVal
- Homo sapiens OEHHA MADL = 0.0082 mg/day ToxVal
- Homo sapiens OEHHA NSRL = 1e-06 mg/day ToxVal
- Homo sapiens OEHHA PHG = 2e-05 mg/L ToxVal
- Homo sapiens MCL = 0.05 mg/L ToxVal
- Homo sapiens Reference Exposure Level = 0.02 mg/kg-day ToxVal
- Homo sapiens Reference Exposure Level = 0.0002 mg/m3 ToxVal
- Homo sapiens cancer slope factor = 510.0 (mg/kg-day)-1 ToxVal
- Homo sapiens cancer unit risk = 150.0 (mg/m3)-1 ToxVal
- Homo sapiens MRL = 0.0003 mg/m3 ToxVal
- Homo sapiens MRL = 5e-06 mg/m3 ToxVal
- Homo sapiens MRL = 0.0009 mg/kg-day ToxVal
- Homo sapiens MRL = 0.005 mg/kg-day ToxVal

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 NPC124099 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 NPC600323

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC124099 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