Natural Product: NPC595797

Natural Product IDNPC595797
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Carthamoside B1
IUPAC Name (2~{S},3~{R},4~{S},5~{S},6~{R})-2-(2,3-dimethoxy-5-methyl-phenoxy)-6-(hydroxymethyl)tetrahydropyran-3,4,5-triol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic 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 UFXDNSRKZFKNBN-ZHZXCYKASA-N
Standard InCHI InChI=1S/C15H22O8/c1-7-4-8(20-2)14(21-3)9(5-7)22-15-13(19)12(18)11(17)10(6-16)23-15/h4-5,10-13,15-19H,6H2,1-3H3/t10-,11-,12+,13-,15-/m1/s1
SMILES COC1=CC(C)=CC(O[C@@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)=C1OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   330.13 Volume:   313.296
?
Van der Waals volume.
Dense:   1.054 LogP:   0.061
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.529
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.333
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   12.0
TPSA:   117.84
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   4.0 Rings:   2.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.554 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.461 Fsp3:   0.6
MCE-18:   51.25
?
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:   0.462 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.318
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.054
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.211 Promiscuous compounds:   0.069

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.377 MDCK Permeability:   -4.902
Pgp-inhibitor:   0.001 Pgp-substrate:   0.257
PAMPA:   0.539
?
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):   0.031
20% Bioavailability (F20%):   0.017 30% Bioavailability (F30%):   0.207
50% Bioavailability (F50%):   0.277

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.753 MRP1:   0.847
Plasma Protein Binding (PPB):   77.27% Volume Distribution (VD):   -0.264
Fu: 22.262%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.996 BCRP inhibitor:   0.004
BSEP inhibitor:   0.144

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.068 CYP2C19-substrate:   0.006
CYP2C9-inhibitor:   0.001 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.002
CYP3A4-inhibitor:   0.525 CYP3A4-substrate:   0.002
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.871
HLM stability:   0.005
?
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):  2.682 Half-life (T1/2):  2.932

ADMET: Toxicity

hERG Blockers:  0.035 hERG Blockers (10um):  0.138
Human Hepatotoxicity (H-HT):  0.655 Drug-induced Liver Injury (DILI):  0.803
AMES Toxicity:  0.852 Rat Oral Acute Toxicity:  0.031
Maximum Recommended Daily Dose:  0.02 Skin Sensitization:  0.99
Carcinogencity:  0.428 Eye Corrosion:  0.003
Eye Irritation:  0.543 Respiratory Toxicity:  0.034
Drug-induced Neurotoxicity:  0.06 Ototoxicity:  0.868
Hematotoxicity:  0.459 Drug-induced Nephrotoxicity:  0.654
Genotoxicity:  0.095 RPMI-8226 Immunitoxicity:  0.104
A549 Cytotoxicity:  0.113 Hek293 Cytotoxicity:  0.105
BCF:   0.355
?
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:   2.51
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.825
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.127
?
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
NPO18311 Carthamus tinctorius Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[22060189]
NPO18311 Carthamus tinctorius Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[22537213]
NPO18311 Carthamus tinctorius Species Asteraceae Eukaryota n.a. flower n.a. PMID[22723874]
NPO18311 Carthamus tinctorius Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[23371463]
NPO18311 Carthamus tinctorius Species Asteraceae Eukaryota Flowers Lasa, China n.a. PMID[24621197]
NPO18311 Carthamus tinctorius Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[27748595]
NPO18311 Carthamus tinctorius Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[39732883]
NPO18311 Carthamus tinctorius Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18311 Carthamus tinctorius Species Asteraceae Eukaryota Bud n.a. n.a. Database[FooDB]
NPO18311 Carthamus tinctorius Species Asteraceae Eukaryota n.a. n.a. Database[FooDB]
NPO18311 Carthamus tinctorius Species Asteraceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO18311 Carthamus tinctorius Species Asteraceae Eukaryota Oil n.a. n.a. Database[FooDB]
NPO18311 Carthamus tinctorius Species Asteraceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO18311 Carthamus tinctorius Species Asteraceae Eukaryota Flower n.a. n.a. Database[FooDB]
NPO18311 Carthamus tinctorius Species Asteraceae Eukaryota n.a. n.a. Database[FooDB]
NPO18311 Carthamus tinctorius Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18311 Carthamus tinctorius Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18311 Carthamus tinctorius Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO18311 Carthamus tinctorius Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO18311 Carthamus tinctorius Species Asteraceae 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 NPC595797 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
0.7083 Intermediate Similarity NPC299144
0.6957 Remote Similarity NPC276195
0.68 Remote Similarity NPC69513
0.6667 Remote Similarity NPC48863
0.6667 Remote Similarity NPC479029
0.6667 Remote Similarity NPC251981
0.6667 Remote Similarity NPC13745
0.6604 Remote Similarity NPC162093
0.6538 Remote Similarity NPC215833
0.6458 Remote Similarity NPC217854
0.6444 Remote Similarity NPC228907
0.6415 Remote Similarity NPC49074
0.6346 Remote Similarity NPC166040
0.62 Remote Similarity NPC25817
0.62 Remote Similarity NPC152722
0.6182 Remote Similarity NPC210478
0.6102 Remote Similarity NPC486107
0.6034 Remote Similarity NPC470236
0.6 Remote Similarity NPC472024
0.6 Remote Similarity NPC153149
0.6 Remote Similarity NPC270849
0.5968 Remote Similarity NPC486102
0.5965 Remote Similarity NPC95392
0.5965 Remote Similarity NPC84013
0.5965 Remote Similarity NPC55715
0.5965 Remote Similarity NPC35877
0.5962 Remote Similarity NPC12308
0.5893 Remote Similarity NPC26653
0.5893 Remote Similarity NPC80600
0.5862 Remote Similarity NPC302378
0.5862 Remote Similarity NPC232673
0.5833 Remote Similarity NPC479030
0.5789 Remote Similarity NPC248355
0.5769 Remote Similarity NPC190730
0.5741 Remote Similarity NPC95292
0.5738 Remote Similarity NPC146803
0.5714 Remote Similarity NPC148273
0.569 Remote Similarity NPC55040
0.569 Remote Similarity NPC104167
0.5686 Remote Similarity NPC192810
0.566 Remote Similarity NPC608788
0.5645 Remote Similarity NPC475096
0.5645 Remote Similarity NPC475084
0.5636 Remote Similarity NPC9912
0.56 Remote Similarity NPC212729
0.56 Remote Similarity NPC604498
0.5556 Remote Similarity NPC221090
0.5556 Remote Similarity NPC145900
0.5536 Remote Similarity NPC218685
0.549 Remote Similarity NPC269242
0.5472 Remote Similarity NPC609376
0.5469 Remote Similarity NPC486104
0.5439 Remote Similarity NPC479028
0.5439 Remote Similarity NPC23084
0.5439 Remote Similarity NPC479031
0.541 Remote Similarity NPC276753
0.541 Remote Similarity NPC205796
0.5385 Remote Similarity NPC294470
0.537 Remote Similarity NPC226712
0.5333 Remote Similarity NPC604162
0.5323 Remote Similarity NPC37468
0.5323 Remote Similarity NPC246947
0.5323 Remote Similarity NPC604095
0.5312 Remote Similarity NPC216129
0.5312 Remote Similarity NPC130449
0.5312 Remote Similarity NPC248132
0.5312 Remote Similarity NPC485147
0.5294 Remote Similarity NPC142319
0.5254 Remote Similarity NPC105827
0.5238 Remote Similarity NPC604892
0.5231 Remote Similarity NPC479447
0.5231 Remote Similarity NPC30432
0.5192 Remote Similarity NPC484157
0.5185 Remote Similarity NPC60589
0.5185 Remote Similarity NPC469708
0.5179 Remote Similarity NPC214454
0.5179 Remote Similarity NPC604209
0.5172 Remote Similarity NPC485268
0.5172 Remote Similarity NPC606892
0.5161 Remote Similarity NPC96294
0.5156 Remote Similarity NPC210192
0.5152 Remote Similarity NPC212290
0.5152 Remote Similarity NPC604833
0.5091 Remote Similarity NPC200092
0.5088 Remote Similarity NPC40377
0.5088 Remote Similarity NPC310661
0.5085 Remote Similarity NPC164599
0.5082 Remote Similarity NPC247146
0.5082 Remote Similarity NPC34456
0.5075 Remote Similarity NPC76128
0.5072 Remote Similarity NPC486106

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC595797 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
0.537 Remote Similarity NPD1091 Pre-clinical

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