Natural Product: NPC497694

Natural Product IDNPC497694
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (3~{S},8~{S},9~{S},10~{R},13~{R},14~{S},17~{R})-17-[(1~{R},2~{E},4~{R})-4-isopropyl-1,5-dimethyl-hexa-2,5-dienyl]-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1~{H}-cyclopenta[a]phenanthren-3-ol
IUPAC Name (3~{S},8~{S},9~{S},10~{R},13~{R},14~{S},17~{R})-17-[(1~{R},2~{E},4~{R})-4-isopropyl-1,5-dimethyl-hexa-2,5-dienyl]-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1~{H}-cyclopenta[a]phenanthren-3-ol
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 BALNAVKTUKBYSD-SWIWIEOMSA-N
Standard InCHI InChI=1S/C30H48O/c1-19(2)24(20(3)4)10-8-21(5)26-12-13-27-25-11-9-22-18-23(31)14-16-29(22,6)28(25)15-17-30(26,27)7/h8-10,20-21,23-28,31H,1,11-18H2,2-7H3/b10-8+/t21-,23+,24-,25+,26-,27+,28+,29+,30-/m1/s1
SMILES C=C(C)[C@@H](/C=C/[C@@H](C)[C@H]1CC[C@H]2[C@@H]3CC=C4C[C@@H](O)CC[C@]4(C)[C@H]3CC[C@]12C)C(C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   424.37 Volume:   494.091
?
Van der Waals volume.
Dense:   0.859 LogP:   6.504
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.758
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.53
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   22.0
TPSA:   20.23
?
Topological Polar Surface Area.
 H-Bond Acceptor:   1.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   1.0

MedChem Properties

QED Drug-Likeness Score:   0.444 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.731 Fsp3:   0.8
MCE-18:   71.556
?
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:   0.987 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.002
?
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:   0.592 Promiscuous compounds:   0.15

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.35 MDCK Permeability:   -4.994
Pgp-inhibitor:   0.088 Pgp-substrate:   0.002
PAMPA:   0.003
?
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%):   0.012 30% Bioavailability (F30%):   0.309
50% Bioavailability (F50%):   0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.012
Plasma Protein Binding (PPB):   98.459% Volume Distribution (VD):   -0.047
Fu: 1.372%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.96
BSEP inhibitor:   0.942

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.071
CYP2D6-inhibitor:   0.052 CYP2D6-substrate:   0.042
CYP3A4-inhibitor:   0.997 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.997
HLM stability:   0.203
?
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):  13.486 Half-life (T1/2):  0.628

ADMET: Toxicity

hERG Blockers:  0.164 hERG Blockers (10um):  0.38
Human Hepatotoxicity (H-HT):  0.6 Drug-induced Liver Injury (DILI):  0.262
AMES Toxicity:  0.071 Rat Oral Acute Toxicity:  0.077
Maximum Recommended Daily Dose:  0.647 Skin Sensitization:  0.926
Carcinogencity:  0.874 Eye Corrosion:  0.185
Eye Irritation:  0.967 Respiratory Toxicity:  0.701
Drug-induced Neurotoxicity:  0.044 Ototoxicity:  0.57
Hematotoxicity:  0.409 Drug-induced Nephrotoxicity:  0.326
Genotoxicity:  0.029 RPMI-8226 Immunitoxicity:  0.056
A549 Cytotoxicity:  0.273 Hek293 Cytotoxicity:  0.587
BCF:   3.074
?
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:   4.621
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.364
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.397
?
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
NPO18098 Topsentia ophiraphidites Species n.a. Eukaryota n.a. n.a. n.a. PMID[7714543]
NPO18098 Topsentia ophiraphidites Species n.a. Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18098 Topsentia ophiraphidites Species n.a. 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 NPC497694 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
0.8571 High Similarity NPC154330
0.84 Intermediate Similarity NPC113733
0.7451 Intermediate Similarity NPC162742
0.7451 Intermediate Similarity NPC304309
0.7451 Intermediate Similarity NPC470228
0.7273 Intermediate Similarity NPC33913
0.7037 Intermediate Similarity NPC230301
0.7037 Intermediate Similarity NPC285893
0.6981 Remote Similarity NPC22105
0.6981 Remote Similarity NPC34019
0.6981 Remote Similarity NPC107059
0.6981 Remote Similarity NPC600590
0.6909 Remote Similarity NPC264245
0.6852 Remote Similarity NPC136188
0.6852 Remote Similarity NPC28657
0.6852 Remote Similarity NPC474216
0.6727 Remote Similarity NPC198968
0.6727 Remote Similarity NPC134847
0.6667 Remote Similarity NPC221758
0.6607 Remote Similarity NPC241290
0.6607 Remote Similarity NPC164840
0.6607 Remote Similarity NPC484739
0.6607 Remote Similarity NPC209944
0.6607 Remote Similarity NPC155986
0.6491 Remote Similarity NPC328714
0.6491 Remote Similarity NPC321381
0.6379 Remote Similarity NPC472265
0.6379 Remote Similarity NPC318495
0.6379 Remote Similarity NPC59453
0.6316 Remote Similarity NPC51014
0.6271 Remote Similarity NPC603646
0.6167 Remote Similarity NPC243985
0.6167 Remote Similarity NPC473943
0.6167 Remote Similarity NPC280710
0.6167 Remote Similarity NPC240650
0.6167 Remote Similarity NPC155011
0.6066 Remote Similarity NPC474164
0.6066 Remote Similarity NPC47761
0.6066 Remote Similarity NPC488870
0.6038 Remote Similarity NPC96319
0.5965 Remote Similarity NPC328313
0.5781 Remote Similarity NPC601043
0.5781 Remote Similarity NPC605412
0.5763 Remote Similarity NPC234193
0.5738 Remote Similarity NPC58063
0.5738 Remote Similarity NPC477522
0.569 Remote Similarity NPC20688
0.5593 Remote Similarity NPC76879
0.5574 Remote Similarity NPC1272
0.5574 Remote Similarity NPC470614
0.5517 Remote Similarity NPC151519
0.5385 Remote Similarity NPC474189
0.5254 Remote Similarity NPC307965
0.5254 Remote Similarity NPC18603
0.5254 Remote Similarity NPC491013
0.5217 Remote Similarity NPC235126
0.5217 Remote Similarity NPC309493
0.5217 Remote Similarity NPC242419
0.5161 Remote Similarity NPC87604
0.5152 Remote Similarity NPC474349
0.5079 Remote Similarity NPC474207
0.5075 Remote Similarity NPC176012
0.507 Remote Similarity NPC486119

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC497694 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
0.7037 Intermediate Similarity NPD7339 Approved
0.6852 Remote Similarity NPD6942 Phase 4
0.6667 Remote Similarity NPD4786 Phase 1
0.6038 Remote Similarity NPD3701 Pre-clinical
0.5517 Remote Similarity NPD3667 Phase 4

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