Natural Product: NPC181197

Natural Product IDNPC181197
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 JIYCHSGWJICLGK-XVAGRUKYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 91597955
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000258] Steroids and steroid derivatives
        • [CHEMONTID:0003569] Pregnane steroids
          • [CHEMONTID:0001468] Gluco/mineralocorticoids, progestogins and derivatives

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 JIYCHSGWJICLGK-XVAGRUKYSA-N
Standard InCHI InChI=1S/C23H32O4/c1-13(27-14(2)24)21-20(26)12-19-17-6-5-15-11-16(25)7-9-22(15,3)18(17)8-10-23(19,21)4/h11,13,17-19,21H,5-10,12H2,1-4H3/t13-,17+,18-,19-,21-,22-,23-/m0/s1
SMILES C[C@@H]([C@H]1C(=O)C[C@H]2[C@@H]3CCC4=CC(=O)CC[C@]4(C)[C@H]3CC[C@]12C)OC(=O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   372.23 Volume:   396.753
?
Van der Waals volume.
Dense:   0.938 LogP:   2.453
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.71
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.761
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   23.0
TPSA:   60.44
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   0.0 Rings:   4.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.679 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.42 Fsp3:   0.783
MCE-18:   71.122
?
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:   0.332 Fluc inhibitor:   0.005
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.018
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.0
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.397 Promiscuous compounds:   0.959

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.546 MDCK Permeability:   -4.746
Pgp-inhibitor:   0.99 Pgp-substrate:   0.001
PAMPA:   0.007
?
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):   0.001
20% Bioavailability (F20%):   0.079 30% Bioavailability (F30%):   0.776
50% Bioavailability (F50%):   0.92

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.016 MRP1:   0.5
Plasma Protein Binding (PPB):   88.254% Volume Distribution (VD):   -0.144
Fu: 11.252%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.798
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.987
CYP2C19-inhibitor:   0.836 CYP2C19-substrate:   0.082
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.493
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.832
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.939
?
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):  8.707 Half-life (T1/2):  0.433

ADMET: Toxicity

hERG Blockers:  0.058 hERG Blockers (10um):  0.334
Human Hepatotoxicity (H-HT):  0.551 Drug-induced Liver Injury (DILI):  0.461
AMES Toxicity:  0.343 Rat Oral Acute Toxicity:  0.279
Maximum Recommended Daily Dose:  0.29 Skin Sensitization:  0.893
Carcinogencity:  0.777 Eye Corrosion:  0.044
Eye Irritation:  0.734 Respiratory Toxicity:  0.247
Drug-induced Neurotoxicity:  0.276 Ototoxicity:  0.282
Hematotoxicity:  0.677 Drug-induced Nephrotoxicity:  0.529
Genotoxicity:  0.747 RPMI-8226 Immunitoxicity:  0.07
A549 Cytotoxicity:  0.085 Hek293 Cytotoxicity:  0.319
BCF:   0.6
?
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:   3.341
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.036
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.432
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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
NPO24749 Abutilon indicum Species Malvaceae Eukaryota n.a. n.a. n.a. DOI[10.1080/11263504.2021.1891151]
NPO24749 Abutilon indicum Species Malvaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23598 Hedera rhombea Species Araliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23598 Hedera rhombea Species Araliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24749 Abutilon indicum Species Malvaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24749 Abutilon indicum Species Malvaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23598 Hedera rhombea Species Araliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24302 Angylocalyx oligophyllus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24749 Abutilon indicum Species Malvaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24424 Tricalysia okelensis Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23598 Hedera rhombea Species Araliaceae 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 NPC181197 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
0.6481 Remote Similarity NPC307176
0.6481 Remote Similarity NPC321874
0.6102 Remote Similarity NPC323765
0.5862 Remote Similarity NPC214043
0.5862 Remote Similarity NPC85774
0.5862 Remote Similarity NPC282593
0.5763 Remote Similarity NPC35734
0.5763 Remote Similarity NPC159577
0.5763 Remote Similarity NPC115023
0.5763 Remote Similarity NPC602429
0.5667 Remote Similarity NPC149203
0.5667 Remote Similarity NPC237712
0.5574 Remote Similarity NPC249312
0.5517 Remote Similarity NPC2634
0.5517 Remote Similarity NPC265782
0.5517 Remote Similarity NPC251929
0.5439 Remote Similarity NPC139397
0.5333 Remote Similarity NPC227064
0.5333 Remote Similarity NPC329043
0.5333 Remote Similarity NPC58841
0.5333 Remote Similarity NPC161423
0.5303 Remote Similarity NPC205860
0.5152 Remote Similarity NPC320514

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC181197 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
0.6481 Remote Similarity NPD4747 Phase 4
0.5902 Remote Similarity NPD5737 Phase 4
0.5738 Remote Similarity NPD5330 Phase 4
0.5556 Remote Similarity NPD6409 Approved
0.5517 Remote Similarity NPD4691 Approved
0.5469 Remote Similarity NPD6672 Phase 4
0.5333 Remote Similarity NPD3666 Phase 4
0.5303 Remote Similarity NPD6684 Phase 4
0.5303 Remote Similarity NPD7334 Approved
0.5303 Remote Similarity NPD7521 Phase 4
0.5224 Remote Similarity NPD6903 Phase 4
0.5082 Remote Similarity NPD4221 Phase 4
0.5072 Remote Similarity NPD7513 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