Natural Product: NPC500056

Natural Product IDNPC500056
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 DTXSID70963597
IUPAC Name (3~{S},6~{a}~{R},6~{b}~{S},8~{R},8~{a}~{S},12~{a}~{R},14~{a}~{R},14~{b}~{R})-8~{a}-(hydroxymethyl)-4,4,6~{a},6~{b},11,11,14~{b}-heptamethyl-1,2,3,4~{a},5,6,7,8,9,10,12,12~{a},14,14~{a}-tetradecahydropicene-3,8-diol
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 YHGVYECWZWIVJC-CHXBPBAWSA-N
Standard InCHI InChI=1S/C30H50O3/c1-25(2)14-15-30(18-31)20(16-25)19-8-9-22-27(5)12-11-23(32)26(3,4)21(27)10-13-28(22,6)29(19,7)17-24(30)33/h8,20-24,31-33H,9-18H2,1-7H3/t20-,21?,22-,23+,24-,27+,28-,29-,30-/m1/s1
SMILES CC1(C)CC[C@]2(CO)[C@H](O)C[C@]3(C)C(=CC[C@@H]4[C@@]5(C)CC[C@H](O)C(C)(C)C5CC[C@]43C)[C@H]2C1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   458.38 Volume:   508.388
?
Van der Waals volume.
Dense:   0.902 LogP:   4.233
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.076
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.823
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   26.0
TPSA:   60.69
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   3.0 Rings:   5.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.415 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.889 Fsp3:   0.933
MCE-18:   104.897
?
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:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.554 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.006
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.0
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.428 Promiscuous compounds:   0.065

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.08 MDCK Permeability:   -4.793
Pgp-inhibitor:   0.002 Pgp-substrate:   0.425
PAMPA:   0.998
?
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):   0.0
20% Bioavailability (F20%):   0.923 30% Bioavailability (F30%):   0.318
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   1.0 MRP1:   0.799
Plasma Protein Binding (PPB):   90.36% Volume Distribution (VD):   -0.004
Fu: 9.312%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.997
OATP1B3 inhibitor:   0.458 BCRP inhibitor:   0.865
BSEP inhibitor:   0.407

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   0.008
CYP2C19-inhibitor:   0.958 CYP2C19-substrate:   0.862
CYP2C9-inhibitor:   0.003 CYP2C9-substrate:   0.003
CYP2D6-inhibitor:   0.03 CYP2D6-substrate:   0.02
CYP3A4-inhibitor:   0.022 CYP3A4-substrate:   0.016
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.66
HLM stability:   0.648
?
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):  8.661 Half-life (T1/2):  0.687

ADMET: Toxicity

hERG Blockers:  0.058 hERG Blockers (10um):  0.254
Human Hepatotoxicity (H-HT):  0.636 Drug-induced Liver Injury (DILI):  0.104
AMES Toxicity:  0.522 Rat Oral Acute Toxicity:  0.657
Maximum Recommended Daily Dose:  0.779 Skin Sensitization:  0.981
Carcinogencity:  0.929 Eye Corrosion:  0.004
Eye Irritation:  0.353 Respiratory Toxicity:  0.94
Drug-induced Neurotoxicity:  0.108 Ototoxicity:  0.589
Hematotoxicity:  0.407 Drug-induced Nephrotoxicity:  0.674
Genotoxicity:  0.331 RPMI-8226 Immunitoxicity:  0.075
A549 Cytotoxicity:  0.86 Hek293 Cytotoxicity:  0.707
BCF:   2.204
?
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:   4.362
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.634
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.128
?
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
NPO17145 Aegiceras corniculatum Species Primulaceae Eukaryota n.a. twig n.a. DOI[10.1021/np50063a031]
NPO17145 Aegiceras corniculatum Species Primulaceae Eukaryota n.a. stem n.a. DOI[10.1021/np50063a031]
NPO17145 Aegiceras corniculatum Species Primulaceae Eukaryota n.a. n.a. n.a. PMID[15165134]
NPO17145 Aegiceras corniculatum Species Primulaceae Eukaryota n.a. twig n.a. PMID[16254827]
NPO17145 Aegiceras corniculatum Species Primulaceae Eukaryota n.a. stem n.a. PMID[16254827]
NPO17145 Aegiceras corniculatum Species Primulaceae Eukaryota n.a. n.a. n.a. PMID[22316191]
NPO17145 Aegiceras corniculatum Species Primulaceae Eukaryota n.a. n.a. n.a. PMID[2778454]
NPO17145 Aegiceras corniculatum Species Primulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO49592 Tapeinosperma pseudojambosa Species Primulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17145 Aegiceras corniculatum Species Primulaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO17145 Aegiceras corniculatum Species Primulaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17145 Aegiceras corniculatum Species Primulaceae 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 NPC500056 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 NPC253807
1.0 High Similarity NPC158662
0.8 Intermediate Similarity NPC311078
0.8 Intermediate Similarity NPC34177
0.7679 Intermediate Similarity NPC101475
0.7455 Intermediate Similarity NPC290598
0.7455 Intermediate Similarity NPC30590
0.7241 Intermediate Similarity NPC235341
0.7241 Intermediate Similarity NPC480924
0.7119 Intermediate Similarity NPC159168
0.7097 Intermediate Similarity NPC488519
0.678 Remote Similarity NPC196753
0.6613 Remote Similarity NPC246708
0.661 Remote Similarity NPC474989
0.6377 Remote Similarity NPC86368
0.629 Remote Similarity NPC238992
0.619 Remote Similarity NPC480950
0.6176 Remote Similarity NPC294360
0.6032 Remote Similarity NPC230295
0.6032 Remote Similarity NPC253402
0.6032 Remote Similarity NPC53744
0.6032 Remote Similarity NPC470588
0.6032 Remote Similarity NPC98386
0.5968 Remote Similarity NPC132478
0.5915 Remote Similarity NPC283343
0.5882 Remote Similarity NPC164349
0.5833 Remote Similarity NPC473160
0.5738 Remote Similarity NPC27765
0.5738 Remote Similarity NPC122418
0.5738 Remote Similarity NPC491014
0.5714 Remote Similarity NPC237344
0.5672 Remote Similarity NPC480946
0.5672 Remote Similarity NPC130577
0.5672 Remote Similarity NPC142415
0.5672 Remote Similarity NPC102683
0.5652 Remote Similarity NPC228784
0.5652 Remote Similarity NPC324341
0.5652 Remote Similarity NPC601810
0.5625 Remote Similarity NPC40394
0.5625 Remote Similarity NPC478657
0.5571 Remote Similarity NPC480919
0.5526 Remote Similarity NPC167383
0.5484 Remote Similarity NPC120098
0.5479 Remote Similarity NPC471433
0.5479 Remote Similarity NPC471432
0.5441 Remote Similarity NPC213412
0.5441 Remote Similarity NPC198664
0.5441 Remote Similarity NPC2539
0.5362 Remote Similarity NPC7260
0.5362 Remote Similarity NPC182797
0.5362 Remote Similarity NPC210037
0.5362 Remote Similarity NPC120968
0.5362 Remote Similarity NPC171203
0.5362 Remote Similarity NPC307426
0.5362 Remote Similarity NPC98442
0.5362 Remote Similarity NPC242468
0.5362 Remote Similarity NPC227467
0.5362 Remote Similarity NPC273621
0.5362 Remote Similarity NPC52169
0.5362 Remote Similarity NPC488562
0.5303 Remote Similarity NPC95594
0.5238 Remote Similarity NPC601696
0.5217 Remote Similarity NPC187722
0.5217 Remote Similarity NPC136313
0.5211 Remote Similarity NPC202728
0.5211 Remote Similarity NPC158059
0.5211 Remote Similarity NPC49776
0.5211 Remote Similarity NPC63118
0.5211 Remote Similarity NPC474436
0.5205 Remote Similarity NPC488520
0.52 Remote Similarity NPC258547
0.5152 Remote Similarity NPC291379
0.5152 Remote Similarity NPC475862
0.5143 Remote Similarity NPC51700
0.5143 Remote Similarity NPC88716
0.5143 Remote Similarity NPC68160
0.5143 Remote Similarity NPC112866
0.5132 Remote Similarity NPC480920
0.5075 Remote Similarity NPC3915
0.5072 Remote Similarity NPC477872
0.5067 Remote Similarity NPC273668
0.5067 Remote Similarity NPC488522

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC500056 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
0.5588 Remote Similarity NPD7645 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