Natural Product: NPC551622

Natural Product IDNPC551622
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Pregna-4,20-dien-3-one
IUPAC Name (8~{S},9~{S},10~{R},13~{R},14~{S},17~{R})-10,13-dimethyl-17-vinyl-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-one
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 CSFSHOOQUIPHRO-NWSAAYAGSA-N
Standard InCHI InChI=1S/C21H30O/c1-4-14-6-8-18-17-7-5-15-13-16(22)9-11-21(15,3)19(17)10-12-20(14,18)2/h4,13-14,17-19H,1,5-12H2,2-3H3/t14-,17-,18-,19-,20+,21-/m0/s1
SMILES C=C[C@H]1CC[C@H]2[C@@H]3CCC4=CC(=O)CC[C@]4(C)[C@H]3CC[C@]12C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   298.23 Volume:   338.427
?
Van der Waals volume.
Dense:   0.881 LogP:   4.578
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.742
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.92
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   22.0
TPSA:   17.07
?
Topological Polar Surface Area.
 H-Bond Acceptor:   1.0
H-Bond Donor:   0.0 Rings:   4.0
Heavy Atoms:   1.0

MedChem Properties

QED Drug-Likeness Score:   0.599 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.117 Fsp3:   0.762
MCE-18:   66.162
?
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:   0.648 Fluc inhibitor:   0.007
?
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
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.841 Promiscuous compounds:   0.335

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.454 MDCK Permeability:   -4.723
Pgp-inhibitor:   0.962 Pgp-substrate:   0.002
PAMPA:   0.002
?
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%):   0.103 30% Bioavailability (F30%):   0.29
50% Bioavailability (F50%):   0.617

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.908 MRP1:   0.045
Plasma Protein Binding (PPB):   97.183% Volume Distribution (VD):   0.065
Fu: 2.729%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.889
BSEP inhibitor:   0.99

ADMET: Metabolism

CYP1A2-inhibitor:   0.111 CYP1A2-substrate:   0.999
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.005
CYP2C9-inhibitor:   0.322 CYP2C9-substrate:   0.808
CYP2D6-inhibitor:   0.837 CYP2D6-substrate:   0.87
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.988
?
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):  12.835 Half-life (T1/2):  0.637

ADMET: Toxicity

hERG Blockers:  0.191 hERG Blockers (10um):  0.584
Human Hepatotoxicity (H-HT):  0.561 Drug-induced Liver Injury (DILI):  0.505
AMES Toxicity:  0.188 Rat Oral Acute Toxicity:  0.28
Maximum Recommended Daily Dose:  0.803 Skin Sensitization:  0.906
Carcinogencity:  0.933 Eye Corrosion:  0.825
Eye Irritation:  0.994 Respiratory Toxicity:  0.923
Drug-induced Neurotoxicity:  0.539 Ototoxicity:  0.229
Hematotoxicity:  0.537 Drug-induced Nephrotoxicity:  0.256
Genotoxicity:  0.618 RPMI-8226 Immunitoxicity:  0.031
A549 Cytotoxicity:  0.139 Hek293 Cytotoxicity:  0.754
BCF:   2.369
?
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:   4.082
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.031
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.832
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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
NPO15968 Annella mollis Species Subergorgiidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15968 Annella mollis Species Subergorgiidae 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 NPC551622 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
0.7955 Intermediate Similarity NPC307176
0.7955 Intermediate Similarity NPC321874
0.7826 Intermediate Similarity NPC282593
0.766 Intermediate Similarity NPC35734
0.766 Intermediate Similarity NPC159577
0.766 Intermediate Similarity NPC115023
0.766 Intermediate Similarity NPC602429
0.75 Intermediate Similarity NPC149203
0.7447 Intermediate Similarity NPC214043
0.7447 Intermediate Similarity NPC85774
0.7347 Intermediate Similarity NPC249312
0.7143 Intermediate Similarity NPC237712
0.6667 Remote Similarity NPC320514
0.6596 Remote Similarity NPC139397
0.6327 Remote Similarity NPC2634
0.6327 Remote Similarity NPC265782
0.6327 Remote Similarity NPC251929
0.6122 Remote Similarity NPC92327
0.6078 Remote Similarity NPC227064
0.6078 Remote Similarity NPC329043
0.6078 Remote Similarity NPC58841
0.6078 Remote Similarity NPC161423
0.6038 Remote Similarity NPC323765
0.5962 Remote Similarity NPC144258
0.5962 Remote Similarity NPC327115
0.5741 Remote Similarity NPC303613
0.5636 Remote Similarity NPC310010
0.5636 Remote Similarity NPC326627
0.5574 Remote Similarity NPC187159
0.5556 Remote Similarity NPC328539
0.5536 Remote Similarity NPC469948
0.5424 Remote Similarity NPC305039
0.5424 Remote Similarity NPC205860
0.5385 Remote Similarity NPC260040
0.5345 Remote Similarity NPC309603
0.5263 Remote Similarity NPC185936
0.5263 Remote Similarity NPC168027
0.5185 Remote Similarity NPC255021
0.5185 Remote Similarity NPC474228
0.5088 Remote Similarity NPC119416

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC551622 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
0.7955 Intermediate Similarity NPD4747 Phase 4
0.6731 Remote Similarity NPD5737 Phase 4
0.6481 Remote Similarity NPD6672 Phase 4
0.6327 Remote Similarity NPD4691 Approved
0.6078 Remote Similarity NPD3666 Phase 4
0.6078 Remote Similarity NPD4221 Phase 4
0.5926 Remote Similarity NPD5330 Phase 4
0.5741 Remote Similarity NPD4693 Phase 3
0.5714 Remote Similarity NPD6409 Approved
0.5636 Remote Similarity NPD4753 Phase 2
0.5636 Remote Similarity NPD6938 Clinical (unspecified phase)
0.5636 Remote Similarity NPD6939 Phase 3
0.5424 Remote Similarity NPD6083 Phase 4
0.5424 Remote Similarity NPD6084 Phase 2
0.5424 Remote Similarity NPD6684 Phase 4
0.5424 Remote Similarity NPD6904 Phase 4
0.5424 Remote Similarity NPD7334 Approved
0.5424 Remote Similarity NPD7521 Phase 4
0.5333 Remote Similarity NPD6903 Phase 4
0.5161 Remote Similarity NPD7513 Clinical (unspecified phase)

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