Natural Product: NPC202839

Natural Product IDNPC202839
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 2-Desmethylcolchicin
IUPAC Name N-[(7S)-2-hydroxy-1,3,10-trimethoxy-9-oxo-6,7-dihydro-5H-benzo[a]heptalen-7-yl]acetamide
Synonyms 2-Desmethylcolchicin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1080
PubChem CID 23757
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0004150] Hydrocarbon derivatives
      • [CHEMONTID:0001650] Tropones

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 DPOVAJCRYIUTBD-HNNXBMFYSA-N
Standard InCHI InChI=1S/C21H23NO6/c1-11(23)22-15-7-5-12-9-18(27-3)20(25)21(28-4)19(12)13-6-8-17(26-2)16(24)10-14(13)15/h6,8-10,15,25H,5,7H2,1-4H3,(H,22,23)/t15-/m0/s1
SMILES CC(=N[C@H]1CCc2cc(c(c(c2-c2ccc(c(=O)cc12)OC)OC)O)OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   385.15 Volume:   388.749
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Van der Waals volume.
Dense:   0.991 LogP:   1.199
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.682
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.872
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The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   20.0
TPSA:   97.58
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Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.618 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.395 Fsp3:   0.333
MCE-18:   64.286
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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:   1 PAINS Alert:   0
Colloidal aggregators:   0.322 Fluc inhibitor:   0.243
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.478
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.301
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.005 Promiscuous compounds:   0.525

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.071 MDCK Permeability:   -4.738
Pgp-inhibitor:   0.033 Pgp-substrate:   0.074
PAMPA:   0.668
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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):   0.163
20% Bioavailability (F20%):   0.092 30% Bioavailability (F30%):   0.136
50% Bioavailability (F50%):   0.966

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.931
Plasma Protein Binding (PPB):   93.399% Volume Distribution (VD):   -0.514
Fu: 7.157%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.997
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.621
BSEP inhibitor:   0.537

ADMET: Metabolism

CYP1A2-inhibitor:   0.998 CYP1A2-substrate:   0.005
CYP2C19-inhibitor:   0.992 CYP2C19-substrate:   0.004
CYP2C9-inhibitor:   0.757 CYP2C9-substrate:   0.014
CYP2D6-inhibitor:   0.94 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   0.004
CYP2B6-substrate:   0.037 CYP2C8-inhibitor:   0.125
HLM stability:   0.376
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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):  1.775 Half-life (T1/2):  1.907

ADMET: Toxicity

hERG Blockers:  0.027 hERG Blockers (10um):  0.081
Human Hepatotoxicity (H-HT):  0.996 Drug-induced Liver Injury (DILI):  0.946
AMES Toxicity:  0.811 Rat Oral Acute Toxicity:  0.599
Maximum Recommended Daily Dose:  0.885 Skin Sensitization:  0.994
Carcinogencity:  0.854 Eye Corrosion:  0.0
Eye Irritation:  0.192 Respiratory Toxicity:  0.751
Drug-induced Neurotoxicity:  0.662 Ototoxicity:  0.502
Hematotoxicity:  0.75 Drug-induced Nephrotoxicity:  0.965
Genotoxicity:  1.0 RPMI-8226 Immunitoxicity:  0.153
A549 Cytotoxicity:  0.021 Hek293 Cytotoxicity:  0.385
BCF:   0.759
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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:   3.563
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.937
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.293
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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
NPO4250 Gloriosa superba Species Colchicaceae Eukaryota n.a. n.a. n.a. DOI[10.1007/s10529-006-0004-9]
NPO22241 Alangium villosum Species Cornaceae Eukaryota stem bark Ceram, Indonesia 1998 PMID[18327911]
NPO22241 Alangium villosum Species Cornaceae Eukaryota n.a. n.a. n.a. PMID[32372642]
NPO4250 Gloriosa superba Species Colchicaceae Eukaryota n.a. n.a. n.a. PMID[32372642]
NPO16993 Pinus roxburghii Species Pinaceae Eukaryota n.a. n.a. n.a. PMID[37199441]
NPO22241 Alangium villosum Species Cornaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11746 Delphinium consolida Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4250 Gloriosa superba Species Colchicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4250 Gloriosa superba Species Colchicaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11746 Delphinium consolida Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO4250 Gloriosa superba Species Colchicaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11746 Delphinium consolida Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO22316 Mycena pura Species Tricholomataceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19531 Chamaecytisus prolifer Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22241 Alangium villosum Species Cornaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17754 Coscoroba coscoroba Species Anatidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11746 Delphinium consolida Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13973 Centaurea behen Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16993 Pinus roxburghii Species Pinaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5913 Cneorum tricoccon Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4250 Gloriosa superba Species Colchicaceae 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
NPT3597 Individual protein Tubulin beta chain Bos taurus Tubulin binding = 50.0 % PMID[3560165]
NPT5136 Individual protein Tubulin beta-1 chain Homo sapiens IC50 = 4800.0 nM PMID[15582446]
NPT518 Protein complex Tubulin Homo sapiens Tubulin binding = 50.0 % PMID[7265112]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT168 Cell line P388 Mus musculus Potency = 13.8 uM kg-1 PMID[7265112]
NPT1178 Cell line KB 3-1 Homo sapiens Inhibition = 24.0 % PMID[15582446]
NPT309 Cell line 1A9 Homo sapiens ED50 = 183.7 nM PMID[17350834]
NPT81 Cell line A549 Homo sapiens ED50 = 950.6 nM PMID[17350834]
NPT83 Cell line MCF7 Homo sapiens ED50 = 361.0 nM PMID[17350834]
NPT858 Cell line LNCaP Homo sapiens ED50 = 324.7 nM PMID[17350834]
NPT306 Cell line PC-3 Homo sapiens ED50 = 475.3 nM PMID[17350834]
NPT90 Cell line DU-145 Homo sapiens ED50 = 611.9 nM PMID[17350834]
NPT91 Cell line KB Homo sapiens ED50 = 146.1 nM PMID[17350834]
NPT759 Cell line H9 Homo sapiens EC50 = 260.0 nM PMID[1919593]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. ED50 = 28977.0 nM PMID[17350834]
NPT24 Organism Human immunodeficiency virus 1 Human immunodeficiency virus 1 IC50 = 260.0 nM PMID[1919593]
NPT2 Others Unspecified n.a. IC50 = 3700.0 nM PMID[2095370]

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
- Mus musculus LD50 = 19.0 mg/kg ToxVal

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 NPC202839 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
0.7344 Intermediate Similarity NPC66678
0.7188 Intermediate Similarity NPC108957
0.7188 Intermediate Similarity NPC14005
0.7188 Intermediate Similarity NPC226941
0.6571 Remote Similarity NPC189782
0.5797 Remote Similarity NPC44642
0.5652 Remote Similarity NPC188120

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC202839 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
0.7188 Intermediate Similarity NPD5089 Approved
0.7188 Intermediate Similarity NPD5090 Phase 4
0.5783 Remote Similarity NPD6841 Approved
0.5783 Remote Similarity NPD6842 Approved
0.5783 Remote Similarity NPD6843 Phase 3
0.5139 Remote Similarity NPD4055 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