Natural Product: NPC90909

Natural Product IDNPC90909
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 CCBXXGSAGQNXHX-FQEVSTJZSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 159549
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000279] Alkaloids and derivatives
      • [CHEMONTID:0000240] Camptothecins

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 CCBXXGSAGQNXHX-FQEVSTJZSA-N
Standard InCHI InChI=1S/C20H16N2O5/c23-6-5-20(26)14-8-16-17-12(7-11-3-1-2-4-15(11)21-17)9-22(16)18(24)13(14)10-27-19(20)25/h1-4,7-8,23,26H,5-6,9-10H2/t20-/m0/s1
SMILES c1ccc2c(c1)cc1Cn3c(-c1n2)cc1c(COC(=O)[C@@]1(CCO)O)c3=O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   364.11 Volume:   353.91
?
Van der Waals volume.
Dense:   1.029 LogP:   0.823
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.339
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.836
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   27.0
TPSA:   101.65
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   2.0 Rings:   5.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.516 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.33 Fsp3:   0.25
MCE-18:   90.72
?
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:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.225 Fluc inhibitor:   0.353
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.99
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.143
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.004 Promiscuous compounds:   0.554

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.338 MDCK Permeability:   -4.835
Pgp-inhibitor:   0.002 Pgp-substrate:   0.55
PAMPA:   0.971
?
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):   0.004
20% Bioavailability (F20%):   0.05 30% Bioavailability (F30%):   0.47
50% Bioavailability (F50%):   0.823

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.544 MRP1:   0.44
Plasma Protein Binding (PPB):   98.098% Volume Distribution (VD):   -0.073
Fu: 1.985%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.132
OATP1B3 inhibitor:   0.233 BCRP inhibitor:   0.612
BSEP inhibitor:   0.948

ADMET: Metabolism

CYP1A2-inhibitor:   0.422 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.089 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.678
CYP3A4-inhibitor:   0.84 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.429
HLM stability:   0.128
?
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):  6.059 Half-life (T1/2):  1.553

ADMET: Toxicity

hERG Blockers:  0.054 hERG Blockers (10um):  0.128
Human Hepatotoxicity (H-HT):  0.981 Drug-induced Liver Injury (DILI):  0.767
AMES Toxicity:  0.963 Rat Oral Acute Toxicity:  0.568
Maximum Recommended Daily Dose:  0.978 Skin Sensitization:  0.988
Carcinogencity:  0.982 Eye Corrosion:  0.0
Eye Irritation:  0.012 Respiratory Toxicity:  0.13
Drug-induced Neurotoxicity:  0.945 Ototoxicity:  0.776
Hematotoxicity:  0.977 Drug-induced Nephrotoxicity:  0.996
Genotoxicity:  1.0 RPMI-8226 Immunitoxicity:  0.713
A549 Cytotoxicity:  0.333 Hek293 Cytotoxicity:  0.887
BCF:   0.573
?
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:   3.355
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.797
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.26
?
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
NPO12582 Camptotheca acuminata Species Nyssaceae Eukaryota n.a. n.a. n.a. DOI[10.1111/j.1399-3054.2000.1100409.x]
NPO654 Dysoxylum acutangulum Species Meliaceae Eukaryota n.a. alkaloids n.a. PMID[19757855]
NPO12582 Camptotheca acuminata Species Nyssaceae Eukaryota n.a. xylem n.a. PMID[21348469]
NPO12582 Camptotheca acuminata Species Nyssaceae Eukaryota n.a. n.a. n.a. PMID[3735324]
NPO12582 Camptotheca acuminata Species Nyssaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO654 Dysoxylum acutangulum Species Meliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12582 Camptotheca acuminata Species Nyssaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12582 Camptotheca acuminata Species Nyssaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO654 Dysoxylum acutangulum Species Meliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12582 Camptotheca acuminata Species Nyssaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO12582 Camptotheca acuminata Species Nyssaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO654 Dysoxylum acutangulum Species Meliaceae 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 NPC90909 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
0.8841 High Similarity NPC129909
0.7013 Intermediate Similarity NPC608071
0.6835 Remote Similarity NPC316181
0.6835 Remote Similarity NPC151781
0.6709 Remote Similarity NPC192674
0.6625 Remote Similarity NPC128115
0.6623 Remote Similarity NPC14325
0.6623 Remote Similarity NPC28848
0.6429 Remote Similarity NPC74562
0.6296 Remote Similarity NPC311858
0.5422 Remote Similarity NPC470003
0.5341 Remote Similarity NPC276661

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC90909 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
0.8841 High Similarity NPD3785 Pre-clinical
0.76 Intermediate Similarity NPD4334 Discontinued
0.6709 Remote Similarity NPD3800 Phase 2
0.6386 Remote Similarity NPD3777 Phase 3
0.6235 Remote Similarity NPD6261 Phase 2
0.6145 Remote Similarity NPD5444 Phase 2
0.593 Remote Similarity NPD4901 Clinical (unspecified phase)
0.5778 Remote Similarity NPD6206 Phase 2
0.5778 Remote Similarity NPD6249 Phase 3
0.573 Remote Similarity NPD5507 Phase 4
0.5714 Remote Similarity NPD6248 Phase 2
0.5667 Remote Similarity NPD5506 Approved
0.5532 Remote Similarity NPD5487 Phase 1
0.5517 Remote Similarity NPD4315 Phase 2
0.5341 Remote Similarity NPD4897 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