Natural Product: NPC110303

Natural Product IDNPC110303
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Abyssinones Iii
IUPAC Name (2S)-2-[2,2-dimethyl-8-(3-methylbut-2-enyl)chromen-6-yl]-7-hydroxy-2,3-dihydrochromen-4-one
Synonyms Abyssinones Iii
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL454077
PubChem CID 10408069
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0003643] 3'-prenylated flavans
            • [CHEMONTID:0003506] 3'-prenylated flavanones

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 BWSXMPVDLMJKKY-QFIPXVFZSA-N
Standard InCHI InChI=1S/C25H26O4/c1-15(2)5-6-16-11-18(12-17-9-10-25(3,4)29-24(16)17)22-14-21(27)20-8-7-19(26)13-23(20)28-22/h5,7-13,22,26H,6,14H2,1-4H3/t22-/m0/s1
SMILES CC(=CCc1cc(cc2C=CC(C)(C)Oc12)[C@@H]1CC(=O)c2ccc(cc2O1)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   390.18 Volume:   418.163
?
Van der Waals volume.
Dense:   0.933 LogP:   5.425
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.258
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.476
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   24.0
TPSA:   55.76
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.674 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.607 Fsp3:   0.32
MCE-18:   79.545
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.99 Fluc inhibitor:   0.831
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.455
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.624
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.3 Promiscuous compounds:   0.125

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.902 MDCK Permeability:   -4.727
Pgp-inhibitor:   0.943 Pgp-substrate:   0.015
PAMPA:   0.272
?
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):   0.006
20% Bioavailability (F20%):   0.926 30% Bioavailability (F30%):   0.998
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.012 MRP1:   0.782
Plasma Protein Binding (PPB):   95.967% Volume Distribution (VD):   0.356
Fu: 3.319%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.982
OATP1B3 inhibitor:   0.982 BCRP inhibitor:   0.993
BSEP inhibitor:   0.988

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.988 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.026
CYP3A4-inhibitor:   0.964 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   1.0
?
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):  7.375 Half-life (T1/2):  1.231

ADMET: Toxicity

hERG Blockers:  0.274 hERG Blockers (10um):  0.601
Human Hepatotoxicity (H-HT):  0.847 Drug-induced Liver Injury (DILI):  0.837
AMES Toxicity:  0.852 Rat Oral Acute Toxicity:  0.889
Maximum Recommended Daily Dose:  0.878 Skin Sensitization:  0.865
Carcinogencity:  0.812 Eye Corrosion:  0.0
Eye Irritation:  0.521 Respiratory Toxicity:  0.963
Drug-induced Neurotoxicity:  0.927 Ototoxicity:  0.619
Hematotoxicity:  0.331 Drug-induced Nephrotoxicity:  0.863
Genotoxicity:  0.979 RPMI-8226 Immunitoxicity:  0.107
A549 Cytotoxicity:  0.705 Hek293 Cytotoxicity:  0.713
BCF:   2.156
?
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:   5.056
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   7.132
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.525
?
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
NPO27807 Calotropis procera Species Apocynaceae Eukaryota root barks n.a. n.a. PMID[15689169]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[21123068]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[28522265]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[29641206]
NPO22444 Ceramium boydenii Species Ceramiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27807 Calotropis procera Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27459 Balanophora tobiracola Species Balanophoraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27807 Calotropis procera Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO27459 Balanophora tobiracola Species Balanophoraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22444 Ceramium boydenii Species Ceramiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27807 Calotropis procera Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1698 Glycyrrhiza inflata Species Fabaceae 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
NPT178 Individual protein Protein-tyrosine phosphatase 1B Homo sapiens IC50 = 72900.0 nM PMID[21571537]
NPT178 Individual protein Protein-tyrosine phosphatase 1B Homo sapiens Inhibition = 43.0 % PMID[28522265]
NPT152 Individual protein Nuclear factor erythroid 2-related factor 2 Homo sapiens FC = 1.84 n.a. PMID[28835349]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT83 Cell line MCF7 Homo sapiens GI = 0.0 % PMID[28522265]
NPT660 Cell line SW480 Homo sapiens GI = 26.0 % PMID[28522265]
NPT65 Cell line HepG2 Homo sapiens GI = 9.0 % PMID[28522265]
NPT113 Cell line RAW264.7 Mus musculus Inhibition = 17.0 % PMID[28522265]

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 NPC110303 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 NPC601247
0.7639 Intermediate Similarity NPC132592
0.75 Intermediate Similarity NPC209040
0.75 Intermediate Similarity NPC111786
0.7424 Intermediate Similarity NPC68104
0.7101 Intermediate Similarity NPC23728
0.6716 Remote Similarity NPC143896
0.6522 Remote Similarity NPC221432
0.6522 Remote Similarity NPC257097
0.6154 Remote Similarity NPC101793
0.5949 Remote Similarity NPC609256
0.5867 Remote Similarity NPC291508
0.575 Remote Similarity NPC160821
0.5714 Remote Similarity NPC39752
0.5694 Remote Similarity NPC39329
0.5694 Remote Similarity NPC51032
0.5625 Remote Similarity NPC227579
0.5625 Remote Similarity NPC214166
0.56 Remote Similarity NPC474033
0.5556 Remote Similarity NPC169591
0.5556 Remote Similarity NPC298223
0.5556 Remote Similarity NPC604412
0.5538 Remote Similarity NPC329225
0.5538 Remote Similarity NPC147686
0.5513 Remote Similarity NPC246948
0.5513 Remote Similarity NPC142405
0.55 Remote Similarity NPC477958
0.5441 Remote Similarity NPC1612
0.5441 Remote Similarity NPC183959
0.5333 Remote Similarity NPC17170
0.5309 Remote Similarity NPC40033
0.5294 Remote Similarity NPC264083
0.5256 Remote Similarity NPC312973
0.525 Remote Similarity NPC474021
0.5244 Remote Similarity NPC233980
0.5244 Remote Similarity NPC481772
0.5244 Remote Similarity NPC197679
0.5147 Remote Similarity NPC476480
0.5147 Remote Similarity NPC84585
0.5135 Remote Similarity NPC164980
0.5059 Remote Similarity NPC43319

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC110303 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
0.5538 Remote Similarity NPD1549 Phase 2

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