Structure

Physi-Chem Properties

Molecular Weight:  462.4
Volume:  536.613
LogP:  6.548
LogD:  4.992
LogS:  -4.516
# Rotatable Bonds:  0
TPSA:  6.48
# H-Bond Aceptor:  2
# H-Bond Donor:  0
# Rings:  5
# Heavy Atoms:  2

MedChem Properties

QED Drug-Likeness Score:  0.34
Synthetic Accessibility Score:  6.419
Fsp3:  0.688
Lipinski Rule-of-5:  Accepted
Pfizer Rule:  Rejected
GSK Rule:  Rejected
BMS Rule:  0
Golden Triangle Rule:  Accepted
Chelating Alert:  0
PAINS Alert:  0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:  -4.845
MDCK Permeability:  1.535604133096058e-05
Pgp-inhibitor:  0.23
Pgp-substrate:  0.895
Human Intestinal Absorption (HIA):  0.307
20% Bioavailability (F20%):  0.998
30% Bioavailability (F30%):  0.023

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):  0.73
Plasma Protein Binding (PPB):  96.54009246826172%
Volume Distribution (VD):  3.422
Pgp-substrate:  1.8789615631103516%

ADMET: Metabolism

CYP1A2-inhibitor:  0.169
CYP1A2-substrate:  0.201
CYP2C19-inhibitor:  0.391
CYP2C19-substrate:  0.439
CYP2C9-inhibitor:  0.034
CYP2C9-substrate:  0.028
CYP2D6-inhibitor:  0.993
CYP2D6-substrate:  0.885
CYP3A4-inhibitor:  0.894
CYP3A4-substrate:  0.345

ADMET: Excretion

Clearance (CL):  11.318
Half-life (T1/2):  0.052

ADMET: Toxicity

hERG Blockers:  0.985
Human Hepatotoxicity (H-HT):  0.988
Drug-inuced Liver Injury (DILI):  0.912
AMES Toxicity:  0.046
Rat Oral Acute Toxicity:  0.61
Maximum Recommended Daily Dose:  0.696
Skin Sensitization:  0.956
Carcinogencity:  0.387
Eye Corrosion:  0.003
Eye Irritation:  0.011
Respiratory Toxicity:  0.927

Download Data

Data Type Select
General Info & Identifiers & Properties  
Structure MOL file  
Source Organisms  
Biological Activities  
Similar NPs/Drugs  

  Natural Product: NPC476559

Natural Product ID:  NPC476559
Common Name*:   Halicyclamine A TFA
IUPAC Name:   n.a.
Synonyms:   Halicyclamine A TFA
Standard InCHIKey:  IONFWERMXIPCJP-VIWLODLHSA-N
Standard InCHI:  InChI=1S/C32H50N2.2C2HF3O2/c1-2-5-10-14-18-23-34-26-29-19-15-11-7-4-6-9-13-17-22-33-24-21-32(31(25-29)28-34)30(27-33)20-16-12-8-3-1;2*3-2(4,5)1(6)7/h2,4-6,9-10,13-14,25,30-32H,1,3,7-8,11-12,15-24,26-28H2;2*(H,6,7)/b5-2-,6-4-,13-9+,14-10-;;/t30-,31+,32-;;/m1../s1
SMILES:  C1CCC[C@@H]2CN3CC/C=C/C=C\CCCCC4=C[C@H]([C@@H]2CC3)CN(C4)CC/C=C\C=C/CC1.C(=O)(C(F)(F)F)O.C(=O)(C(F)(F)F)O
Synthetic Gene Cluster:   n.a.
ChEMBL Identifier:   n.a.
PubChem CID:   49797541
Chemical Classification**:  
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000195] Piperidines

*Note: the InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
**Note: the Chemical Classification was calculated by NPClassifier Version 1.5. Reference: PMID:34662515.

  Species Source

Organism ID Organism Name Taxonomy Level Family SuperKingdom Isolation Part Collection Location Collection Time Reference
NPO33243 Amphimedon sp. Species Niphatidae Eukaryota n.a. Iojima Island, the Satsunan Islands, southern Japan (3047 N; 13017 E) n.a. PMID[15497958]
NPO33243 Amphimedon sp. Species Niphatidae Eukaryota n.a. n.a. n.a. PMID[17067172]
NPO33243 Amphimedon sp. Species Niphatidae Eukaryota n.a. Republic of Palau 2006; 2007 PMID[20681583]
NPO33243 Amphimedon sp. Species Niphatidae Eukaryota n.a. n.a. n.a. PMID[28207259]
NPO33243 Amphimedon sp. Species Niphatidae Eukaryota n.a. n.a. n.a. PMID[7714542]
NPO33243 Amphimedon sp. Species Niphatidae Eukaryota n.a. n.a. n.a. PMID[9599281]

☑ 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 NP ID 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

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT168 Cell Line P388 Mus musculus IC50 = 0.45 ug/ml PMID[15497958]

☑ Note for Activity Records:
☉ The quantitative biological activities were primarily integrated from ChEMBL (Version-30) database and were also directly collected from PubMed literature. PubMed PMID was provided as the reference link for each activity record.

  Chemically structural similarity: I. Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes 4,3285 NPs with experimentally-derived bioactivity available in NPASS)

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules. Tc lies between [0, 1] where '1' indicates the highest similarity. What is Tanimoto coefficient

●  The left chart: Distribution of similarity level between NPC476559 and all remaining natural products in the NPASS database.
●  The right table: Most similar natural products (Tc>=0.56 or Top200).

Similarity Score Similarity Level Natural Product ID
0.8689 High Similarity NPC82919
0.8525 High Similarity NPC231129
0.7973 Intermediate Similarity NPC476560
0.7237 Intermediate Similarity NPC473695
0.7237 Intermediate Similarity NPC473446
0.7222 Intermediate Similarity NPC472543
0.7206 Intermediate Similarity NPC472544
0.6667 Remote Similarity NPC265789
0.6667 Remote Similarity NPC308050
0.6623 Remote Similarity NPC125828
0.6538 Remote Similarity NPC259989
0.6538 Remote Similarity NPC174803
0.6506 Remote Similarity NPC234822
0.6506 Remote Similarity NPC78058
0.6506 Remote Similarity NPC135639
0.6506 Remote Similarity NPC61321
0.6506 Remote Similarity NPC143344
0.65 Remote Similarity NPC120699
0.65 Remote Similarity NPC127430
0.6494 Remote Similarity NPC476904
0.6447 Remote Similarity NPC21773
0.6389 Remote Similarity NPC206660
0.6386 Remote Similarity NPC171639
0.6341 Remote Similarity NPC474122
0.6329 Remote Similarity NPC7214
0.622 Remote Similarity NPC12035
0.6203 Remote Similarity NPC63284
0.6125 Remote Similarity NPC214125
0.6125 Remote Similarity NPC320667
0.6118 Remote Similarity NPC207048
0.6098 Remote Similarity NPC211322
0.6066 Remote Similarity NPC177470
0.6047 Remote Similarity NPC76283
0.6 Remote Similarity NPC17810
0.5978 Remote Similarity NPC470382
0.5978 Remote Similarity NPC119225
0.5978 Remote Similarity NPC25033
0.5978 Remote Similarity NPC476261
0.5978 Remote Similarity NPC471635
0.5972 Remote Similarity NPC42477
0.5952 Remote Similarity NPC152039
0.5952 Remote Similarity NPC118329
0.5915 Remote Similarity NPC472830
0.5904 Remote Similarity NPC268580
0.5902 Remote Similarity NPC144023
0.589 Remote Similarity NPC219621
0.589 Remote Similarity NPC477461
0.589 Remote Similarity NPC477459
0.5882 Remote Similarity NPC476679
0.5882 Remote Similarity NPC215474
0.5882 Remote Similarity NPC472312
0.5876 Remote Similarity NPC473254
0.5854 Remote Similarity NPC244256
0.5854 Remote Similarity NPC86452
0.5824 Remote Similarity NPC470926
0.5814 Remote Similarity NPC104070
0.5795 Remote Similarity NPC157479
0.5773 Remote Similarity NPC58200
0.5765 Remote Similarity NPC231986
0.5765 Remote Similarity NPC329782
0.5753 Remote Similarity NPC311809
0.5753 Remote Similarity NPC317778
0.5747 Remote Similarity NPC471867
0.5738 Remote Similarity NPC183670
0.5733 Remote Similarity NPC473959
0.5714 Remote Similarity NPC77890
0.5714 Remote Similarity NPC132858
0.5714 Remote Similarity NPC470893
0.5714 Remote Similarity NPC267203
0.5682 Remote Similarity NPC147513
0.5672 Remote Similarity NPC201713
0.5667 Remote Similarity NPC266298
0.5652 Remote Similarity NPC145707
0.5645 Remote Similarity NPC218918
0.5645 Remote Similarity NPC120926
0.5641 Remote Similarity NPC23721
0.5631 Remote Similarity NPC143173
0.5618 Remote Similarity NPC166458
0.5616 Remote Similarity NPC475716
0.561 Remote Similarity NPC34672
0.5606 Remote Similarity NPC124851
0.56 Remote Similarity NPC145715
0.56 Remote Similarity NPC474086

  Chemically structural similarity: II. Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC476559 and all drugs/candidates.
●  The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

Similarity Score Similarity Level Drug ID Developmental Stage
0.6447 Remote Similarity NPD5365 Phase 2
0.6235 Remote Similarity NPD5916 Discontinued
0.6145 Remote Similarity NPD4026 Approved
0.6145 Remote Similarity NPD4027 Approved
0.6071 Remote Similarity NPD4170 Approved
0.6071 Remote Similarity NPD4169 Approved
0.6071 Remote Similarity NPD4701 Clinical (unspecified phase)
0.6067 Remote Similarity NPD3346 Approved
0.6067 Remote Similarity NPD3344 Approved
0.6023 Remote Similarity NPD3345 Approved
0.6 Remote Similarity NPD8262 Approved
0.5977 Remote Similarity NPD4406 Approved
0.5977 Remote Similarity NPD4409 Approved
0.5977 Remote Similarity NPD4636 Approved
0.5952 Remote Similarity NPD3035 Approved
0.5854 Remote Similarity NPD4144 Approved
0.5854 Remote Similarity NPD4147 Approved
0.5843 Remote Similarity NPD5675 Discontinued
0.5833 Remote Similarity NPD5371 Approved
0.5833 Remote Similarity NPD5372 Approved
0.5824 Remote Similarity NPD3000 Approved
0.5824 Remote Similarity NPD2998 Approved
0.5824 Remote Similarity NPD2997 Approved
0.5814 Remote Similarity NPD4635 Approved
0.5797 Remote Similarity NPD3727 Discontinued
0.5795 Remote Similarity NPD5252 Clinical (unspecified phase)
0.5778 Remote Similarity NPD5656 Clinical (unspecified phase)
0.5747 Remote Similarity NPD5178 Approved
0.5745 Remote Similarity NPD5964 Phase 2
0.5745 Remote Similarity NPD5963 Phase 2
0.5714 Remote Similarity NPD529 Approved
0.5699 Remote Similarity NPD6549 Approved
0.5699 Remote Similarity NPD6548 Approved
0.5682 Remote Similarity NPD2208 Approved
0.5682 Remote Similarity NPD2205 Approved
0.5625 Remote Similarity NPD4813 Approved
0.5625 Remote Similarity NPD815 Approved
0.5625 Remote Similarity NPD4263 Approved
0.5625 Remote Similarity NPD816 Approved

  Bioactivity similarity: Similar Natural Products in NPASS

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