Natural Product: NPC7563

Natural Product IDNPC7563
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Crassumolide B
IUPAC Name (3aS,6E,10Z,14E,15aS)-10-(hydroxymethyl)-6,14-dimethyl-3-methylidene-3a,4,5,8,9,12,13,15a-octahydrocyclotetradeca[b]furan-2-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL573105
PubChem CID 25156697
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001283] Terpene lactones
          • [CHEMONTID:0001538] Diterpene lactones
            • [CHEMONTID:0002502] Cembranolides

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 ZMVCRUREHOFWFQ-QXRWMXRCSA-N
Standard InCHI InChI=1S/C20H28O3/c1-14-6-4-8-17(13-21)9-5-7-15(2)12-19-18(11-10-14)16(3)20(22)23-19/h6,9,12,18-19,21H,3-5,7-8,10-11,13H2,1-2H3/b14-6+,15-12+,17-9-/t18-,19-/m0/s1
SMILES OC/C/1=CCC/C(=C/[C@@H]2OC(=O)C(=C)[C@@H]2CC/C(=C/CC1)/C)/C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   316.2 Volume:   350.552
?
Van der Waals volume.
Dense:   0.902 LogP:   2.973
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.84
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.786
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   20.0
TPSA:   46.53
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.447 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.416 Fsp3:   0.55
MCE-18:   32.71
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.279 Fluc inhibitor:   0.156
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.01
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.05
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.719 Promiscuous compounds:   0.246

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.715 MDCK Permeability:   -4.666
Pgp-inhibitor:   0.956 Pgp-substrate:   0.006
PAMPA:   0.024
?
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):   0.158
20% Bioavailability (F20%):   0.105 30% Bioavailability (F30%):   0.912
50% Bioavailability (F50%):   0.925

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.008 MRP1:   0.822
Plasma Protein Binding (PPB):   79.081% Volume Distribution (VD):   -0.025
Fu: 15.475%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.006
BSEP inhibitor:   0.996

ADMET: Metabolism

CYP1A2-inhibitor:   0.002 CYP1A2-substrate:   0.126
CYP2C19-inhibitor:   0.07 CYP2C19-substrate:   0.002
CYP2C9-inhibitor:   0.948 CYP2C9-substrate:   0.006
CYP2D6-inhibitor:   0.24 CYP2D6-substrate:   0.355
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.361
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.999
HLM stability:   0.633
?
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):  8.618 Half-life (T1/2):  1.178

ADMET: Toxicity

hERG Blockers:  0.007 hERG Blockers (10um):  0.041
Human Hepatotoxicity (H-HT):  0.622 Drug-induced Liver Injury (DILI):  0.883
AMES Toxicity:  0.114 Rat Oral Acute Toxicity:  0.024
Maximum Recommended Daily Dose:  0.328 Skin Sensitization:  0.993
Carcinogencity:  0.28 Eye Corrosion:  0.349
Eye Irritation:  0.97 Respiratory Toxicity:  0.028
Drug-induced Neurotoxicity:  0.351 Ototoxicity:  0.221
Hematotoxicity:  0.195 Drug-induced Nephrotoxicity:  0.573
Genotoxicity:  0.013 RPMI-8226 Immunitoxicity:  0.089
A549 Cytotoxicity:  0.06 Hek293 Cytotoxicity:  0.248
BCF:   1.857
?
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:   4.314
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.966
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.357
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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
NPO27251 Lobophytum crassum Species Alcyoniidae Eukaryota n.a. south china sea n.a. PMID[18512986]
NPO27251 Lobophytum crassum Species Alcyoniidae Eukaryota n.a. n.a. n.a. PMID[18973388]
NPO27251 Lobophytum crassum Species Alcyoniidae Eukaryota n.a. n.a. n.a. PMID[9548852]
NPO27251 Lobophytum crassum Species Alcyoniidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27251 Lobophytum crassum Species Alcyoniidae 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
NPT65 Cell line HepG2 Homo sapiens IC50 > 5.0 ug.mL-1 PMID[22037378]
NPT82 Cell line MDA-MB-231 Homo sapiens IC50 > 5.0 ug.mL-1 PMID[20420415]
NPT83 Cell line MCF7 Homo sapiens IC50 > 5.0 ug.mL-1 PMID[22037378]
NPT81 Cell line A549 Homo sapiens IC50 > 5.0 ug.mL-1 PMID[16933872]
NPT1031 Cell line Ca9-22 Homo sapiens IC50 > 5.0 ug.mL-1 PMID[22037378]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 5.0 ug.mL-1 PMID[18973388]

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 NPC7563 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
0.814 Intermediate Similarity NPC58956
0.814 Intermediate Similarity NPC163003
0.814 Intermediate Similarity NPC295633
0.814 Intermediate Similarity NPC269206
0.7 Intermediate Similarity NPC476355
0.6481 Remote Similarity NPC267231
0.6481 Remote Similarity NPC250315
0.6275 Remote Similarity NPC229825
0.6275 Remote Similarity NPC602858
0.6226 Remote Similarity NPC116177
0.6111 Remote Similarity NPC123360
0.6078 Remote Similarity NPC196653
0.6 Remote Similarity NPC21469
0.6 Remote Similarity NPC481909
0.5965 Remote Similarity NPC93763
0.5962 Remote Similarity NPC471465
0.5882 Remote Similarity NPC140287
0.5862 Remote Similarity NPC108816
0.5741 Remote Similarity NPC470256
0.5686 Remote Similarity NPC167881
0.5686 Remote Similarity NPC98557
0.566 Remote Similarity NPC24417
0.56 Remote Similarity NPC601805
0.5536 Remote Similarity NPC194871
0.5517 Remote Similarity NPC470755
0.5517 Remote Similarity NPC298801
0.549 Remote Similarity NPC235906
0.5472 Remote Similarity NPC603669
0.5439 Remote Similarity NPC158756
0.5439 Remote Similarity NPC601035
0.5385 Remote Similarity NPC306041
0.5283 Remote Similarity NPC171204
0.5283 Remote Similarity NPC606745
0.5263 Remote Similarity NPC473390
0.5263 Remote Similarity NPC608845
0.5254 Remote Similarity NPC20713
0.5254 Remote Similarity NPC488116
0.5185 Remote Similarity NPC611318
0.5172 Remote Similarity NPC488117
0.5172 Remote Similarity NPC178702
0.5167 Remote Similarity NPC469910
0.5091 Remote Similarity NPC473715
0.5091 Remote Similarity NPC59097

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC7563 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