Natural Product: NPC205934

Natural Product IDNPC205934
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Mahanimbine
IUPAC Name 3,5-dimethyl-3-(4-methylpent-3-enyl)-11H-pyrano[3,2-a]carbazole
Synonyms Mahanimbine; Rel-(+)-Mahanimbine
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL495873
PubChem CID 167963
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000211] Indoles and derivatives
        • [CHEMONTID:0000210] Carbazoles

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 HTNVFUBCWIYPJN-UHFFFAOYSA-N
Standard InCHI InChI=1S/C23H25NO/c1-15(2)8-7-12-23(4)13-11-18-21-19(14-16(3)22(18)25-23)17-9-5-6-10-20(17)24-21/h5-6,8-11,13-14,24H,7,12H2,1-4H3
SMILES CC(=CCCC1(C)C=Cc2c3c(cc(C)c2O1)c1ccccc1[nH]3)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   331.19 Volume:   370.834
?
Van der Waals volume.
Dense:   0.893 LogP:   6.374
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.54
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -7.111
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The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   21.0
TPSA:   25.02
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.541 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.359 Fsp3:   0.304
MCE-18:   70.533
?
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:   0.994 Fluc inhibitor:   0.337
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.879
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.925
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.01 Promiscuous compounds:   0.335

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.755 MDCK Permeability:   -4.528
Pgp-inhibitor:   0.923 Pgp-substrate:   0.056
PAMPA:   0.077
?
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%):   0.019 30% Bioavailability (F30%):   0.083
50% Bioavailability (F50%):   0.782

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.963 MRP1:   0.975
Plasma Protein Binding (PPB):   98.135% Volume Distribution (VD):   0.39
Fu: 1.789%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   0.956 BCRP inhibitor:   0.475
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.321 CYP1A2-substrate:   0.49
CYP2C19-inhibitor:   0.701 CYP2C19-substrate:   0.045
CYP2C9-inhibitor:   0.742 CYP2C9-substrate:   0.254
CYP2D6-inhibitor:   0.997 CYP2D6-substrate:   0.57
CYP3A4-inhibitor:   0.376 CYP3A4-substrate:   0.896
CYP2B6-substrate:   0.007 CYP2C8-inhibitor:   1.0
HLM stability:   0.839
?
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):  8.097 Half-life (T1/2):  0.534

ADMET: Toxicity

hERG Blockers:  0.475 hERG Blockers (10um):  0.703
Human Hepatotoxicity (H-HT):  0.735 Drug-induced Liver Injury (DILI):  0.707
AMES Toxicity:  0.681 Rat Oral Acute Toxicity:  0.562
Maximum Recommended Daily Dose:  0.562 Skin Sensitization:  0.725
Carcinogencity:  0.718 Eye Corrosion:  0.0
Eye Irritation:  0.823 Respiratory Toxicity:  0.92
Drug-induced Neurotoxicity:  0.857 Ototoxicity:  0.63
Hematotoxicity:  0.549 Drug-induced Nephrotoxicity:  0.774
Genotoxicity:  0.126 RPMI-8226 Immunitoxicity:  0.1
A549 Cytotoxicity:  0.35 Hek293 Cytotoxicity:  0.405
BCF:   2.59
?
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:   4.888
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.774
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.718
?
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
NPO17480 Murraya siamensis Species Rutaceae Eukaryota n.a. twig n.a. PMID[10757740]
NPO17480 Murraya siamensis Species Rutaceae Eukaryota n.a. flower n.a. PMID[10757740]
NPO17480 Murraya siamensis Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[10757740]
NPO17480 Murraya siamensis Species Rutaceae Eukaryota n.a. leaf n.a. PMID[10757740]
NPO3118 Murraya euchrestifolia Species Rutaceae Eukaryota root bark Kuantaochi, Nantou Hsien, Taiwan n.a. PMID[10924160]
NPO3118 Murraya euchrestifolia Species Rutaceae Eukaryota stem bark;fruit n.a. n.a. PMID[10924160]
NPO3364 Murraya koenigii Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[12662104]
NPO3364 Murraya koenigii Species Rutaceae Eukaryota n.a. Sri Lankan n.a. PMID[23376010]
NPO3364 Murraya koenigii Species Rutaceae Eukaryota fruits Coimbatore, India 2010-JUN PMID[23691929]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. leaf n.a. PMID[24354205]
NPO12182 Murraya exotica Species Rutaceae Eukaryota n.a. leaf n.a. PMID[24354205]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. twig n.a. PMID[24354205]
NPO12182 Murraya exotica Species Rutaceae Eukaryota n.a. twig n.a. PMID[24354205]
NPO3364 Murraya koenigii Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[27136692]
NPO12182 Murraya exotica Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[29303577]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[34964904]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[36529712]
NPO3364 Murraya koenigii Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[39414752]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12182 Murraya exotica Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2715.1 Murraya paniculata var. exotica Varieties Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3118 Murraya euchrestifolia Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3364 Murraya koenigii Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17480 Murraya siamensis Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2715.1 Murraya paniculata var. exotica Varieties Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO3118 Murraya euchrestifolia Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO3364 Murraya koenigii Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO17480 Murraya siamensis Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12182 Murraya exotica Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2715.1 Murraya paniculata var. exotica Varieties Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3364 Murraya koenigii Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3118 Murraya euchrestifolia Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17480 Murraya siamensis Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3364 Murraya koenigii Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO17480 Murraya siamensis Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO12182 Murraya exotica Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO17480 Murraya siamensis Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3118 Murraya euchrestifolia Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12182 Murraya exotica Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3364 Murraya koenigii Species Rutaceae 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
NPT2797 Individual protein Pancreatic lipase Homo sapiens IC50 = 17900.0 nM PMID[27908755]
NPT51 Individual protein Microtubule-associated protein tau Homo sapiens Potency = 8912.5 nM PubChem BioAssay data set
NPT51 Individual protein Microtubule-associated protein tau Homo sapiens Potency = 15848.9 nM PubChem BioAssay data set
NPT197 Protein-protein interaction Menin/Histone-lysine N-methyltransferase MLL Homo sapiens Potency = 3162.3 nM PubChem BioAssay data set
NPT43 Individual protein Tyrosinase Agaricus bisporus Inhibition = 6.2 % PMID[23376010]
NPT43 Individual protein Tyrosinase Agaricus bisporus Inhibition = 2.7 % PMID[23376010]
NPT43 Individual protein Tyrosinase Agaricus bisporus Inhibition = -0.4 % PMID[23376010]
NPT43 Individual protein Tyrosinase Agaricus bisporus Inhibition = -3.2 % PMID[23376010]
NPT43 Individual protein Tyrosinase Agaricus bisporus Inhibition = -1.3 % PMID[23376010]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT2 Others Unspecified n.a. IC50 = 1400.0 nM PMID[23376010]
NPT2 Others Unspecified n.a. Inhibition = 63.9 % PMID[23376010]
NPT2 Others Unspecified n.a. Inhibition = 43.3 % PMID[23376010]
NPT2 Others Unspecified n.a. Potency n.a. 8912.5 nM PubChem BioAssay data set

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 NPC205934 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 NPC267766
0.7656 Intermediate Similarity NPC476106
0.7385 Intermediate Similarity NPC72211
0.7273 Intermediate Similarity NPC475085
0.7121 Intermediate Similarity NPC470930
0.7119 Intermediate Similarity NPC43787
0.6575 Remote Similarity NPC484121
0.6026 Remote Similarity NPC484125
0.5857 Remote Similarity NPC70259
0.5679 Remote Similarity NPC484118
0.5506 Remote Similarity NPC475253
0.5352 Remote Similarity NPC476044
0.5342 Remote Similarity NPC267423
0.527 Remote Similarity NPC475112
0.5072 Remote Similarity NPC162484
0.5072 Remote Similarity NPC64751
0.5065 Remote Similarity NPC484120

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC205934 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
NPD

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