Natural Product: NPC268992

Natural Product IDNPC268992
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Tetrahydroaltersolanol C
IUPAC Name (2R,3S,4aS,9aS,10S)-2,3,8,10-tetrahydroxy-6-methoxy-3-methyl-1,2,4,4a,9a,10-hexahydroanthracen-9-one
Synonyms Tetrahydroaltersolanol C
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2011660
PubChem CID 57332236
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0000018] Anthracenes

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 GYPNJHLHXZTDFI-FMFJDBFUSA-N
Standard InCHI InChI=1S/C16H20O6/c1-16(21)6-10-8(5-12(16)18)15(20)13-9(14(10)19)3-7(22-2)4-11(13)17/h3-4,8,10,12,14,17-19,21H,5-6H2,1-2H3/t8-,10-,12+,14+,16-/m0/s1
SMILES COc1cc2[C@@H](O)[C@H]3C[C@](C)(O)[C@@H](C[C@@H]3C(=O)c2c(c1)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   308.13 Volume:   301.818
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Van der Waals volume.
Dense:   1.021 LogP:   1.066
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.523
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.885
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The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   17.0
TPSA:   107.22
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Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   4.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.61 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.181 Fsp3:   0.562
MCE-18:   74.76
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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:   0.179 Fluc inhibitor:   0.09
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.162
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.006
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.213 Promiscuous compounds:   0.645

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.056 MDCK Permeability:   -4.711
Pgp-inhibitor:   0.001 Pgp-substrate:   0.442
PAMPA:   0.99
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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):   0.129
20% Bioavailability (F20%):   0.279 30% Bioavailability (F30%):   0.743
50% Bioavailability (F50%):   0.996

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.659
Plasma Protein Binding (PPB):   53.391% Volume Distribution (VD):   0.119
Fu: 45.742%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.996
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.276
BSEP inhibitor:   0.102

ADMET: Metabolism

CYP1A2-inhibitor:   0.047 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.033 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.641 CYP2C9-substrate:   0.143
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.381
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.315
HLM stability:   0.096
?
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):  5.723 Half-life (T1/2):  2.84

ADMET: Toxicity

hERG Blockers:  0.052 hERG Blockers (10um):  0.277
Human Hepatotoxicity (H-HT):  0.842 Drug-induced Liver Injury (DILI):  0.528
AMES Toxicity:  0.886 Rat Oral Acute Toxicity:  0.7
Maximum Recommended Daily Dose:  0.611 Skin Sensitization:  0.936
Carcinogencity:  0.828 Eye Corrosion:  0.001
Eye Irritation:  0.695 Respiratory Toxicity:  0.926
Drug-induced Neurotoxicity:  0.084 Ototoxicity:  0.717
Hematotoxicity:  0.614 Drug-induced Nephrotoxicity:  0.78
Genotoxicity:  0.963 RPMI-8226 Immunitoxicity:  0.197
A549 Cytotoxicity:  0.602 Hek293 Cytotoxicity:  0.578
BCF:   0.428
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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:   3.06
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.368
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.701
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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
NPO32908 Alternaria sp. Species Pleosporaceae Eukaryota n.a. n.a. n.a. PMID[18494522]
NPO32908 Alternaria sp. Species Pleosporaceae Eukaryota n.a. n.a. n.a. PMID[22276679]
NPO32908 Alternaria sp. Species Pleosporaceae Eukaryota n.a. n.a. n.a. PMID[25265160]
NPO32908 Alternaria sp. Species Pleosporaceae Eukaryota n.a. n.a. n.a. PMID[26841051]
NPO32908 Alternaria sp. Species Pleosporaceae Eukaryota n.a. n.a. n.a. PMID[30794407]
NPO32908 Alternaria sp. Species Pleosporaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

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
NPT393 Cell line HCT-116 Homo sapiens IC50 > 100000.0 nM PMID[19453174]
NPT306 Cell line PC-3 Homo sapiens IC50 > 100000.0 nM PMID[20643902]
NPT65 Cell line HepG2 Homo sapiens IC50 > 100000.0 nM PMID[16124776]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 100000.0 nM PMID[22276679]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 65000.0 nM PMID[22276679]
NPT2 Others Unspecified n.a. IC50 > 100000 nM PubChem BioAssay data set

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 NPC268992 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 NPC470337
1.0 High Similarity NPC113608
1.0 High Similarity NPC470338
0.7143 Intermediate Similarity NPC155302
0.7143 Intermediate Similarity NPC604497
0.7143 Intermediate Similarity NPC608598
0.7018 Intermediate Similarity NPC51824
0.6393 Remote Similarity NPC470339
0.6271 Remote Similarity NPC225854
0.5606 Remote Similarity NPC472055
0.5574 Remote Similarity NPC68727
0.5574 Remote Similarity NPC600297
0.5556 Remote Similarity NPC486426
0.5556 Remote Similarity NPC486427
0.5556 Remote Similarity NPC486428
0.5536 Remote Similarity NPC486434
0.5469 Remote Similarity NPC161947
0.5469 Remote Similarity NPC606196
0.5469 Remote Similarity NPC611096
0.5263 Remote Similarity NPC600511
0.5156 Remote Similarity NPC470340

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC268992 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